Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 4535194, 18 pages
https://doi.org/10.1155/2017/4535194
Review Article

Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies

College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing 100044, China

Correspondence should be addressed to Jinhua Zhang; nc.ude.utjb@hjgnahz

Received 28 January 2017; Revised 22 May 2017; Accepted 31 May 2017; Published 28 June 2017

Academic Editor: Javier Egea

Copyright © 2017 Tian Tian et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. Corridoni, K. O. Arseneau, and F. Cominelli, “Inflammatory bowel disease,” Immunology Letters, vol. 161, no. 2, pp. 231–235, 2014. View at Publisher · View at Google Scholar · View at Scopus
  2. E. V. Loftus Jr. and W. J. Sandborn, “Epidemiology of inflammatory bowel disease,” Gastroenterology Clinics of North America, vol. 31, no. 1, pp. 1–20, 2002. View at Publisher · View at Google Scholar · View at Scopus
  3. S. C. Ng, W. Tang, J. Y. Ching et al., “Incidence and phenotype of inflammatory bowel disease based on results from the Asia-Pacific Crohn’s and colitis epidemiology study,” Gastroenterology, vol. 145, no. 1, pp. 158–165, 2013, e152. View at Publisher · View at Google Scholar · View at Scopus
  4. Z. Zeng, Z. Zhu, Y. Yang et al., “Incidence and clinical characteristics of inflammatory bowel disease in a developed region of Guangdong Province, China: a prospective population-based study,” Journal of Gastroenterology and Hepatology, vol. 28, no. 7, pp. 1148–1153, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. C. Huttenhower, A. D. Kostic, and R. J. Xavier, “Inflammatory bowel disease as a model for translating the microbiome,” Immunity, vol. 40, no. 6, pp. 843–854, 2014. View at Publisher · View at Google Scholar · View at Scopus
  6. N. A. Molodecky, I. S. Soon, D. M. Rabi et al., “Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review,” Gastroenterology, vol. 142, no. 1, pp. 46–54, 2012, e42; quiz e30. View at Publisher · View at Google Scholar · View at Scopus
  7. P. Goyette, C. Labbe, T. T. Trinh, R. J. Xavier, and J. D. Rioux, “Molecular pathogenesis of inflammatory bowel disease: genotypes, phenotypes and personalized medicine,” Annals of Medicine, vol. 39, no. 3, pp. 177–199, 2007. View at Google Scholar
  8. A. Dahan, G. L. Amidon, and E. M. Zimmermann, “Drug targeting strategies for the treatment of inflammatory bowel disease: a mechanistic update,” Expert Review of Clinical Immunology, vol. 6, no. 4, pp. 543–550, 2010. View at Google Scholar
  9. K. Bedard and K. H. Krause, “The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology,” Physiological Reviews, vol. 87, no. 1, pp. 245–313, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. M. A. Alzoghaibi, “Concepts of oxidative stress and antioxidant defense in Crohn’s disease,” World Journal of Gastroenterology, vol. 19, no. 39, pp. 6540–6547, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. J. Pravda, “Radical induction theory of ulcerative colitis,” World Journal of Gastroenterology, vol. 11, no. 16, pp. 2371–2384, 2005. View at Publisher · View at Google Scholar
  12. E. A. Novak and K. P. Mollen, “Mitochondrial dysfunction in inflammatory bowel disease,” Frontiers in Cell and Development Biology, vol. 3, p. 62, 2015. View at Publisher · View at Google Scholar
  13. R. O. Poyton, P. R. Castello, K. A. Ball, D. K. Woo, and N. Pan, “Mitochondria and hypoxic signaling: a new view,” Annals of the New York Academy of Sciences, vol. 1177, pp. 48–56, 2009. View at Google Scholar
  14. Y. Chen and S. B. Gibson, “Is mitochondrial generation of reactive oxygen species a trigger for autophagy?” Autophagy, vol. 4, no. 2, pp. 246–248, 2008. View at Google Scholar
  15. R. Scherz-Shouval and Z. Elazar, “ROS, mitochondria and the regulation of autophagy,” Trends in Cell Biology, vol. 17, no. 9, pp. 422–427, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. A. C. Kulkarni, P. Kuppusamy, and N. Parinandi, “Oxygen, the lead actor in the pathophysiologic drama: enactment of the trinity of normoxia, hypoxia, and hyperoxia in disease and therapy,” Antioxidants & Redox Signaling, vol. 9, no. 10, pp. 1717–1730, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. E. J. Swindle and D. D. Metcalfe, “The role of reactive oxygen species and nitric oxide in mast cell-dependent inflammatory processes,” Immunological Reviews, vol. 217, pp. 186–205, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. S. O'Neill, J. Brault, M. J. Stasia, and U. G. Knaus, “Genetic disorders coupled to ROS deficiency,” Redox Biology, vol. 6, pp. 135–156, 2015. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Sasaki and T. Joh, “Oxidative stress and ischemia-reperfusion injury in gastrointestinal tract and antioxidant, protective agents,” Journal of Clinical Biochemistry and Nutrition, vol. 40, no. 1, pp. 1–12, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. T. A. Ullman and S. H. Itzkowitz, “Intestinal inflammation and cancer,” Gastroenterology, vol. 140, no. 6, pp. 1807–1816, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. M. D. Barrachina, J. Panes, and J. V. Esplugues, “Role of nitric oxide in gastrointestinal inflammatory and ulcerative diseases: perspective for drugs development,” Current Pharmaceutical Design, vol. 7, no. 1, pp. 31–48, 2001. View at Publisher · View at Google Scholar · View at Scopus
  22. D. Rachmilewitz, F. Karmeli, R. Eliakim et al., “Enhanced gastric nitric oxide synthase activity in duodenal ulcer patients,” Gut, vol. 35, no. 10, pp. 1394–1397, 1994. View at Publisher · View at Google Scholar
  23. P. C. Konturek, J. Kania, G. Burnat, E. G. Hahn, and S. J. Konturek, “Prostaglandins as mediators of COX-2 derived carcinogenesis in gastrointestinal tract,” Journal of Physiology and Pharmacology, vol. 56, Supplement 5, pp. 57–73, 2005. View at Google Scholar
  24. E. Bergmark, C. J. Calleman, F. He, and L. G. Costa, “Determination of hemoglobin adducts in humans occupationally exposed to acrylamide,” Toxicology and Applied Pharmacology, vol. 120, no. 1, pp. 45–54, 1993. View at Publisher · View at Google Scholar · View at Scopus
  25. C. G. Fraga and P. I. Oteiza, “Iron toxicity and antioxidant nutrients,” Toxicology, vol. 180, no. 1, pp. 23–32, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Zapolska-Downar, A. Kosmider, and M. Naruszewicz, “Trans fatty acids induce apoptosis in human endothelial cells,” Journal of Physiology and Pharmacology, vol. 56, no. 4, pp. 611–625, 2005. View at Google Scholar
  27. A. Bhattacharyya, R. Chattopadhyay, S. Mitra, and S. E. Crowe, “Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases,” Physiological Reviews, vol. 94, no. 2, pp. 329–354, 2014. View at Publisher · View at Google Scholar · View at Scopus
  28. L. A. Ridnour, J. S. Isenberg, M. G. Espey, D. D. Thomas, D. D. Roberts, and D. A. Wink, “Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 37, pp. 13147–13152, 2005. View at Google Scholar
  29. M. Valko, D. Leibfritz, J. Moncol, M. T. Cronin, M. Mazur, and J. Telser, “Free radicals and antioxidants in normal physiological functions and human disease,” The International Journal of Biochemistry & Cell Biology, vol. 39, no. 1, pp. 44–84, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Valko, H. Morris, M. Mazur, P. Rapta, and R. F. Bilton, “Oxygen free radical generating mechanisms in the colon: do the semiquinones of vitamin K play a role in the aetiology of colon cancer?” Biochimica et Biophysica Acta, vol. 1527, no. 3, pp. 161–166, 2001. View at Google Scholar
  31. V. Chiurchiu and M. Maccarrone, “Chronic inflammatory disorders and their redox control: from molecular mechanisms to therapeutic opportunities,” Antioxidants & Redox Signaling, vol. 15, no. 9, pp. 2605–2641, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. Y. C. Peng, C. L. Hsu, C. F. Tung et al., “Chemiluminescence assay of mucosal reactive oxygen species in gastric cancer, ulcer and antral mucosa,” Hepato-Gastroenterology, vol. 55, no. 82-83, pp. 770–773, 2008. View at Google Scholar
  33. M. B. Grisham, “Oxidants and free radicals in inflammatory bowel disease,” Lancet, vol. 344, no. 8926, pp. 859–861, 1994. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Inokuma, M. Haraguchi, F. Fujita, Y. Tajima, and T. Kanematsu, “Oxidative stress and tumor progression in colorectal cancer,” Hepato-Gastroenterology, vol. 56, no. 90, pp. 343–347, 2009. View at Google Scholar
  35. I. Fridovich, “Superoxide anion radical (O2-.), superoxide dismutases, and related matters,” The Journal of Biological Chemistry, vol. 272, no. 30, pp. 18515–18517, 1997. View at Publisher · View at Google Scholar · View at Scopus
  36. Y. Li, T. T. Huang, E. J. Carlson et al., “Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase,” Nature Genetics, vol. 11, no. 4, pp. 376–381, 1995. View at Publisher · View at Google Scholar · View at Scopus
  37. S. L. Marklund, “Human copper-containing superoxide dismutase of high molecular weight,” Proceedings of the National Academy of Sciences of the United States of America, vol. 79, no. 24, pp. 7634–7638, 1982. View at Google Scholar
  38. L. Kruidenier, I. Kuiper, W. van Duijn et al., “Differential mucosal expression of three superoxide dismutase isoforms in inflammatory bowel disease,” The Journal of Pathology, vol. 201, no. 1, pp. 7–16, 2003. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Naito, T. Yoshikawa, T. Ando et al., “Changes in superoxide dismutase activity in the gastric mucosa of peptic ulcer patients,” Journal of Clinical Gastroenterology, vol. 14, Supplement 1, pp. S131–S134, 1992. View at Publisher · View at Google Scholar
  40. B. Beltran, P. Nos, F. Dasi et al., “Mitochondrial dysfunction, persistent oxidative damage, and catalase inhibition in immune cells of naive and treated Crohn’s disease,” Inflammatory Bowel Diseases, vol. 16, no. 1, pp. 76–86, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. K. M. Sakthivel and C. Guruvayoorappan, “Protective effect of Acacia ferruginea against ulcerative colitis via modulating inflammatory mediators, cytokine profile and NF-kappaB signal transduction pathways,” Journal of Environmental Pathology, Toxicology and Oncology, vol. 33, no. 2, pp. 83–98, 2014. View at Publisher · View at Google Scholar · View at Scopus
  42. R. Dayer, B. B. Fischer, R. I. Eggen, and S. D. Lemaire, “The peroxiredoxin and glutathione peroxidase families in Chlamydomonas reinhardtii,” Genetics, vol. 179, no. 1, pp. 41–57, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. F. F. Chu, R. S. Esworthy, and J. H. Doroshow, “Role of Se-dependent glutathione peroxidases in gastrointestinal inflammation and cancer,” Free Radical Biology & Medicine, vol. 36, no. 12, pp. 1481–1495, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. A. A. Te Velde, I. Pronk, F. de Kort, and P. C. Stokkers, “Glutathione peroxidase 2 and aquaporin 8 as new markers for colonic inflammation in experimental colitis and inflammatory bowel diseases: an important role for H2O2?” European Journal of Gastroenterology & Hepatology, vol. 20, no. 6, pp. 555–560, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Mangerich, P. C. Dedon, J. G. Fox, S. R. Tannenbaum, and G. N. Wogan, “Chemistry meets biology in colitis-associated carcinogenesis,” Free Radical Research, vol. 47, no. 11, pp. 958–986, 2013. View at Publisher · View at Google Scholar · View at Scopus
  46. F. Hiller, K. Besselt, S. Deubel, R. Brigelius-Flohé, and A. P. Kipp, “GPx2 induction is mediated through STAT transcription factors during acute colitis,” Inflammatory Bowel Diseases, vol. 21, no. 9, pp. 2078–2089, 2015. View at Publisher · View at Google Scholar · View at Scopus
  47. R. S. Esworthy, R. Aranda, M. G. Martin, J. H. Doroshow, S. W. Binder, and F. F. Chu, “Mice with combined disruption of Gpx1 and Gpx2 genes have colitis,” American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 281, no. 3, pp. G848–G855, 2001. View at Google Scholar
  48. D. M. Tham, J. C. Whitin, K. K. Kim, S. X. Zhu, and H. J. Cohen, “Expression of extracellular glutathione peroxidase in human and mouse gastrointestinal tract,” The American Journal of Physiology, vol. 275, no. 6, Part 1, pp. G1463–G1471, 1998. View at Google Scholar
  49. M. Schrader and H. D. Fahimi, “Peroxisomes and oxidative stress,” Biochimica et Biophysica Acta, vol. 1763, no. 12, pp. 1755–1766, 2006. View at Google Scholar
  50. J. M. Atack and D. J. Kelly, “Oxidative stress in Campylobacter jejuni: responses, resistance and regulation,” Future Microbiology, vol. 4, no. 6, pp. 677–690, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Mori, H. Suzuki, M. Suzuki, A. Kai, S. Miura, and H. Ishii, “Catalase and superoxide dismutase secreted from Helicobacter pylori,” Helicobacter, vol. 2, no. 2, pp. 100–105, 1997. View at Publisher · View at Google Scholar
  52. J. G. Fox, F. E. Dewhirst, J. G. Tully et al., “Helicobacter hepaticus sp. nov., a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice,” Journal of Clinical Microbiology, vol. 32, no. 5, pp. 1238–1245, 1994. View at Google Scholar
  53. M. Iborra, I. Moret, F. Rausell et al., “Role of oxidative stress and antioxidant enzymes in Crohn's disease,” Biochemical Society Transactions, vol. 39, no. 4, pp. 1102–1106, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. D. Chang, Z. L. Hu, L. Zhang et al., “Association of catalase genotype with oxidative stress in the predication of colorectal cancer: modification by epidemiological factors,” Biomedical and Environmental Sciences, vol. 25, no. 2, pp. 156–162, 2012. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Monari, J. Foschi, C. Calabrese et al., “Implications of antioxidant enzymes in human gastric neoplasms,” International Journal of Molecular Medicine, vol. 24, no. 5, pp. 693–700, 2009. View at Google Scholar
  56. J. G. LeBlanc, S. del Carmen, A. Miyoshi et al., “Use of superoxide dismutase and catalase producing lactic acid bacteria in TNBS induced Crohn’s disease in mice,” Journal of Biotechnology, vol. 151, no. 3, pp. 287–293, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. A. de Moreno de LeBlanc, J. G. LeBlanc, G. Perdigon et al., “Oral administration of a catalase-producing Lactococcus lactis can prevent a chemically induced colon cancer in mice,” Journal of Medical Microbiology, vol. 57, Part 1, pp. 100–105, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. A. G. Hall, “Review: the role of glutathione in the regulation of apoptosis,” European Journal of Clinical Investigation, vol. 29, no. 3, pp. 238–245, 1999. View at Publisher · View at Google Scholar · View at Scopus
  59. V. Prabhu and C. Guruvayoorappan, “Protective effect of marine mangrove Rhizophora apiculata on acetic acid induced experimental colitis by regulating anti-oxidant enzymes, inflammatory mediators and nuclear factor-kappa B subunits,” International Immunopharmacology, vol. 18, no. 1, pp. 124–134, 2014. View at Google Scholar
  60. E. A. Socca, A. Luiz-Ferreira, F. M. de Faria et al., “Inhibition of tumor necrosis factor-alpha and cyclooxigenase-2 by Isatin: a molecular mechanism of protection against TNBS-induced colitis in rats,” Chemico-Biological Interactions, vol. 209, pp. 48–55, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. C. L. Rise, V. V. Prabhu, and C. Guruvayoorappan, “Effect of marine mangrove Avicennia marina (Forssk.) Vierh against acetic acid-induced ulcerative colitis in experimental mice,” Journal of Environmental Pathology, Toxicology and Oncology, vol. 31, no. 2, pp. 179–192, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. H. S. Oz, T. S. Chen, C. J. McClain, and W. J. de Villiers, “Antioxidants as novel therapy in a murine model of colitis,” The Journal of Nutritional Biochemistry, vol. 16, no. 5, pp. 297–304, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. R. J. Reiter, “Melatonin: lowering the high price of free radicals,” News in Physiological Sciences, vol. 15, pp. 246–250, 2000. View at Google Scholar
  64. R. J. Reiter, S. D. Paredes, L. C. Manchester, and D. X. Tan, “Reducing oxidative/nitrosative stress: a newly-discovered genre for melatonin,” Critical Reviews in Biochemistry and Molecular Biology, vol. 44, no. 4, pp. 175–200, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. D. Bonnefont-Rousselot and F. Collin, “Melatonin: action as antioxidant and potential applications in human disease and aging,” Toxicology, vol. 278, no. 1, pp. 55–67, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Dominguez-Rodriguez, P. Abreu-Gonzalez, J. J. Sanchez-Sanchez, J. C. Kaski, and R. J. Reiter, “Melatonin and circadian biology in human cardiovascular disease,” Journal of Pineal Research, vol. 49, no. 1, pp. 14–22, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. R. E. Rosenstein, S. R. Pandi-Perumal, V. Srinivasan, D. W. Spence, G. M. Brown, and D. P. Cardinali, “Melatonin as a therapeutic tool in ophthalmology: implications for glaucoma and uveitis,” Journal of Pineal Research, vol. 49, no. 1, pp. 1–13, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. O. Ioannidis, I. Varnalidis, G. Paraskevas, and D. Botsios, “Nutritional modulation of the inflammatory bowel response,” Digestion, vol. 84, no. 2, pp. 89–101, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Rezaie, R. D. Parker, and M. Abdollahi, “Oxidative stress and pathogenesis of inflammatory bowel disease: an epiphenomenon or the cause?” Digestive Diseases and Sciences, vol. 52, no. 9, pp. 2015–2021, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Hengstermann, L. Valentini, L. Schaper et al., “Altered status of antioxidant vitamins and fatty acids in patients with inactive inflammatory bowel disease,” Clinical Nutrition, vol. 27, no. 4, pp. 571–578, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. E. D. Harris, “Regulation of antioxidant enzymes,” The FASEB Journal, vol. 6, no. 9, pp. 2675–2683, 1992. View at Google Scholar
  72. J. E. Brown, H. Khodr, R. C. Hider, and C. A. Rice-Evans, “Structural dependence of flavonoid interactions with Cu2+ ions: implications for their antioxidant properties,” The Biochemical Journal, vol. 330, Part 3, pp. 1173–1178, 1998. View at Google Scholar
  73. Y. Hanasaki, S. Ogawa, and S. Fukui, “The correlation between active oxygens scavenging and antioxidative effects of flavonoids,” Free Radical Biology & Medicine, vol. 16, no. 6, pp. 845–850, 1994. View at Publisher · View at Google Scholar · View at Scopus
  74. R. H. Duerr, K. D. Taylor, S. R. Brant et al., “A genome-wide association study identifies IL23R as an inflammatory bowel disease gene,” Science, vol. 314, no. 5804, pp. 1461–1463, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Hampe, A. Franke, P. Rosenstiel et al., “A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1,” Nature Genetics, vol. 39, no. 2, pp. 207–211, 2007. View at Google Scholar
  76. W. T. Uniken Venema, M. D. Voskuil, G. Dijkstra, R. K. Weersma, and E. A. Festen, “The genetic background of inflammatory bowel disease: from correlation to causality,” The Journal of Pathology, vol. 241, no. 2, pp. 146–158, 2017. View at Publisher · View at Google Scholar
  77. A. Franke, T. Balschun, T. H. Karlsen et al., “Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility,” Nature Genetics, vol. 40, no. 11, pp. 1319–1323, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. S. A. Fisher, M. Tremelling, C. A. Anderson et al., “Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn’s disease,” Nature Genetics, vol. 40, no. 6, pp. 710–712, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. M. S. Silverberg, J. H. Cho, J. D. Rioux et al., “Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study,” Nature Genetics, vol. 41, no. 2, pp. 216–220, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. E. A. Festen, P. C. Stokkers, C. C. van Diemen et al., “Genetic analysis in a Dutch study sample identifies more ulcerative colitis susceptibility loci and shows their additive role in disease risk,” The American Journal of Gastroenterology, vol. 105, no. 2, pp. 395–402, 2010. View at Google Scholar
  81. C. A. Anderson, G. Boucher, C. W. Lees et al., “Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47,” Nature Genetics, vol. 43, no. 3, pp. 246–252, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. Y. Ogura, D. K. Bonen, N. Inohara et al., “A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease,” Nature, vol. 411, no. 6837, pp. 603–606, 2001. View at Publisher · View at Google Scholar · View at Scopus
  83. L. Jostins, S. Ripke, R. K. Weersma et al., “Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease,” Nature, vol. 491, no. 7422, pp. 119–124, 2012. View at Publisher · View at Google Scholar · View at Scopus
  84. K. Yamazaki, D. McGovern, J. Ragoussis et al., “Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn’s disease,” Human Molecular Genetics, vol. 14, no. 22, pp. 3499–3506, 2005. View at Publisher · View at Google Scholar · View at Scopus
  85. A. Franke, D. P. McGovern, J. C. Barrett et al., “Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci,” Nature Genetics, vol. 42, no. 12, pp. 1118–1125, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. J. D. Rioux, R. J. Xavier, K. D. Taylor et al., “Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis,” Nature Genetics, vol. 39, no. 5, pp. 596–604, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. M. Parkes, J. C. Barrett, N. J. Prescott et al., “Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility,” Nature Genetics, vol. 39, no. 7, pp. 830–832, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Orvedahl, R. Sumpter Jr., G. Xiao et al., “Image-based genome-wide siRNA screen identifies selective autophagy factors,” Nature, vol. 480, no. 7375, pp. 113–117, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. S. K. Yang, M. Hong, W. Zhao et al., “Genome-wide association study of Crohn’s disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations,” Gut, vol. 63, no. 1, pp. 80–87, 2014. View at Google Scholar
  90. K. L. VanDussen, T. C. Liu, D. Li et al., “Genetic variants synthesize to produce paneth cell phenotypes that define subtypes of Crohn’s disease,” Gastroenterology, vol. 146, no. 1, pp. 200–209, 2014. View at Publisher · View at Google Scholar · View at Scopus
  91. S. A. McCarroll, A. Huett, P. Kuballa et al., “Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease,” Nature Genetics, vol. 40, no. 9, pp. 1107–1112, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. Y. Tong, H. Yamaguchi, E. Giaime et al., “Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 21, pp. 9879–9884, 2010. View at Google Scholar
  93. A. C. Villani, M. Lemire, G. Fortin et al., “Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility,” Nature Genetics, vol. 41, no. 1, pp. 71–76, 2009. View at Google Scholar
  94. D. P. McGovern, A. Gardet, L. Torkvist et al., “Genome-wide association identifies multiple ulcerative colitis susceptibility loci,” Nature Genetics, vol. 42, no. 4, pp. 332–337, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. D. Franchimont, S. Vermeire, H. El Housni et al., “Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis,” Gut, vol. 53, no. 7, pp. 987–992, 2004. View at Publisher · View at Google Scholar · View at Scopus
  96. S. W. Kim, E. S. Kim, C. M. Moon et al., “Genetic polymorphisms of IL-23R and IL-17A and novel insights into their associations with inflammatory bowel disease,” Gut, vol. 60, no. 11, pp. 1527–1536, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. Y. Li, Q. Mao, L. Shen et al., “Interleukin-23 receptor genetic polymorphisms and Crohn’s disease susceptibility: a meta-analysis,” Inflammation Research, vol. 59, no. 8, pp. 607–614, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. K. Wang, H. Zhang, S. Kugathasan et al., “Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn disease,” American Journal of Human Genetics, vol. 84, no. 3, pp. 399–405, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. E. O. Glocker, D. Kotlarz, K. Boztug et al., “Inflammatory bowel disease and mutations affecting the interleukin-10 receptor,” The New England Journal of Medicine, vol. 361, no. 21, pp. 2033–2045, 2009. View at Publisher · View at Google Scholar · View at Scopus
  100. T. Kosaka, J. Yoshino, K. Inui et al., “Involvement of NAD(P)H:quinone oxidoreductase 1 and superoxide dismutase polymorphisms in ulcerative colitis,” DNA and Cell Biology, vol. 28, no. 12, pp. 625–631, 2009. View at Publisher · View at Google Scholar · View at Scopus
  101. R. D. Mittal, P. K. Manchanda, H. K. Bid, and U. C. Ghoshal, “Analysis of polymorphisms of tumor necrosis factor-alpha and polymorphic xenobiotic metabolizing enzymes in inflammatory bowel disease: study from northern India,” Journal of Gastroenterology and Hepatology, vol. 22, no. 6, pp. 920–924, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. E. Hertervig, A. Nilsson, and J. Seidegard, “The expression of glutathione transferase mu in patients with inflammatory bowel disease,” Scandinavian Journal of Gastroenterology, vol. 29, no. 8, pp. 729–735, 1994. View at Google Scholar
  103. A. Karban, C. Hartman, R. Eliakim et al., “Paraoxonase (PON)1 192R allele carriage is associated with reduced risk of inflammatory bowel disease,” Digestive Diseases and Sciences, vol. 52, no. 10, pp. 2707–2715, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. T. Arisawa, T. Tahara, T. Shibata et al., “Nrf2 gene promoter polymorphism is associated with ulcerative colitis in a Japanese population,” Hepato-Gastroenterology, vol. 55, no. 82-83, pp. 394–397, 2008. View at Google Scholar
  105. J. Beisner, E. F. Stange, and J. Wehkamp, “Innate antimicrobial immunity in inflammatory bowel diseases,” Expert Review of Clinical Immunology, vol. 6, no. 5, pp. 809–818, 2010. View at Google Scholar
  106. W. S. Garrett, J. I. Gordon, and L. H. Glimcher, “Homeostasis and inflammation in the intestine,” Cell, vol. 140, no. 6, pp. 859–870, 2010. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Fukata and M. Arditi, “The role of pattern recognition receptors in intestinal inflammation,” Mucosal Immunology, vol. 6, no. 3, pp. 451–463, 2013. View at Publisher · View at Google Scholar · View at Scopus
  108. L. Pastorelli, C. De Salvo, J. R. Mercado, M. Vecchi, and T. T. Pizarro, “Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics,” Frontiers in Immunology, vol. 4, p. 280, 2013. View at Publisher · View at Google Scholar · View at Scopus
  109. J. K. Andersen, “Oxidative stress in neurodegeneration: cause or consequence?” Nature Medicine, vol. 10, Supplement, pp. S18–S25, 2004. View at Publisher · View at Google Scholar · View at Scopus
  110. A. Banan, S. Choudhary, Y. Zhang, J. Z. Fields, and A. Keshavarzian, “Ethanol-induced barrier dysfunction and its prevention by growth factors in human intestinal monolayers: evidence for oxidative and cytoskeletal mechanisms,” The Journal of Pharmacology and Experimental Therapeutics, vol. 291, no. 3, pp. 1075–1085, 1999. View at Google Scholar
  111. R. Rao, R. D. Baker, and S. S. Baker, “Inhibition of oxidant-induced barrier disruption and protein tyrosine phosphorylation in Caco-2 cell monolayers by epidermal growth factor,” Biochemical Pharmacology, vol. 57, no. 6, pp. 685–695, 1999. View at Publisher · View at Google Scholar · View at Scopus
  112. J. Heidemann, W. Domschke, T. Kucharzik, and C. Maaser, “Intestinal microvascular endothelium and innate immunity in inflammatory bowel disease: a second line of defense?” Infection and Immunity, vol. 74, no. 10, pp. 5425–5432, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. N. Senhaji, K. Kojok, Y. Darif, C. Fadainia, and Y. Zaid, “The contribution of CD40/CD40L axis in inflammatory bowel disease: an update,” Frontiers in Immunology, vol. 6, p. 529, 2015. View at Publisher · View at Google Scholar · View at Scopus
  114. K. L. Wallace, L. B. Zheng, Y. Kanazawa, and D. Q. Shih, “Immunopathology of inflammatory bowel disease,” World Journal of Gastroenterology, vol. 20, no. 1, pp. 6–21, 2014. View at Publisher · View at Google Scholar · View at Scopus
  115. J. T. Lu, A. T. Xu, J. Shen, and Z. H. Ran, “Crosstalk between intestinal epithelial cell and adaptive immune cell in intestinal mucosal immunity,” Journal of Gastroenterology and Hepatology, vol. 32, 2017. View at Publisher · View at Google Scholar
  116. R. J. Xavier and D. K. Podolsky, “Unravelling the pathogenesis of inflammatory bowel disease,” Nature, vol. 448, no. 7152, pp. 427–434, 2007. View at Publisher · View at Google Scholar · View at Scopus
  117. D. C. Baumgart and W. J. Sandborn, “Crohn’s disease,” Lancet, vol. 380, no. 9853, pp. 1590–1605, 2012. View at Publisher · View at Google Scholar · View at Scopus
  118. F. Biasi, G. Leonarduzzi, P. I. Oteiza, and G. Poli, “Inflammatory bowel disease: mechanisms, redox considerations, and therapeutic targets,” Antioxidants & Redox Signaling, vol. 19, no. 14, pp. 1711–1747, 2013. View at Publisher · View at Google Scholar · View at Scopus
  119. G. Rogler, K. Brand, D. Vogl et al., “Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa,” Gastroenterology, vol. 115, no. 2, pp. 357–369, 1998. View at Publisher · View at Google Scholar · View at Scopus
  120. R. Ungaro, S. Mehandru, P. B. Allen, L. Peyrin-Biroulet, and J. F. Colombel, “Ulcerative colitis,” Lancet, vol. 389, 2016. View at Google Scholar
  121. F. Heller, P. Florian, C. Bojarski et al., “Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution,” Gastroenterology, vol. 129, no. 2, pp. 550–564, 2005. View at Publisher · View at Google Scholar · View at Scopus
  122. P. Pacher, J. S. Beckman, and L. Liaudet, “Nitric oxide and peroxynitrite in health and disease,” Physiological Reviews, vol. 87, no. 1, pp. 315–424, 2007. View at Publisher · View at Google Scholar · View at Scopus
  123. C. G. Knutson, A. Mangerich, Y. Zeng et al., “Chemical and cytokine features of innate immunity characterize serum and tissue profiles in inflammatory bowel disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 26, pp. E2332–E2341, 2013. View at Google Scholar
  124. C. F. Babbs, “Oxygen radicals in ulcerative colitis,” Free Radical Biology & Medicine, vol. 13, no. 2, pp. 169–181, 1992. View at Publisher · View at Google Scholar · View at Scopus
  125. S. Muthupalani, Z. Ge, Y. Feng et al., “Systemic macrophage depletion inhibits Helicobacter bilis-induced proinflammatory cytokine-mediated typhlocolitis and impairs bacterial colonization dynamics in a BALB/c Rag2−/− mouse model of inflammatory bowel disease,” Infection and Immunity, vol. 80, no. 12, pp. 4388–4397, 2012. View at Publisher · View at Google Scholar · View at Scopus
  126. T. Kelder, J. H. Stroeve, S. Bijlsma, M. Radonjic, and G. Roeselers, “Correlation network analysis reveals relationships between diet-induced changes in human gut microbiota and metabolic health,” Nutrition & Diabetes, vol. 4, article e122, 2014. View at Publisher · View at Google Scholar · View at Scopus
  127. S. Falcinelli, A. Rodiles, S. Unniappan et al., “Probiotic treatment reduces appetite and glucose level in the zebrafish model,” Scientific Reports, vol. 6, p. 18061, 2016. View at Google Scholar
  128. M. Rajilic-Stojanovic, D. M. Jonkers, A. Salonen et al., “Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena?” The American Journal of Gastroenterology, vol. 110, no. 2, pp. 278–287, 2015. View at Publisher · View at Google Scholar · View at Scopus
  129. G. Tomasello, M. Mazzola, A. Leone et al., “Nutrition, oxidative stress and intestinal dysbiosis: influence of diet on gut microbiota in inflammatory bowel diseases,” Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czech Republic, vol. 160, no. 4, pp. 461–466, 2016. View at Publisher · View at Google Scholar · View at Scopus
  130. T. T. Macdonald and G. Monteleone, “Immunity, inflammation, and allergy in the gut,” Science, vol. 307, no. 5717, pp. 1920–1925, 2005. View at Publisher · View at Google Scholar · View at Scopus
  131. M. H. Giaffer, C. D. Holdsworth, and B. I. Duerden, “Virulence properties of Escherichia coli strains isolated from patients with inflammatory bowel disease,” Gut, vol. 33, no. 5, pp. 646–650, 1992. View at Publisher · View at Google Scholar
  132. C. N. Bernstein and F. Shanahan, “Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases,” Gut, vol. 57, no. 9, pp. 1185–1191, 2008. View at Publisher · View at Google Scholar · View at Scopus
  133. R. J. Chiodini, H. J. Van Kruiningen, W. R. Thayer, R. S. Merkal, and J. A. Coutu, “Possible role of mycobacteria in inflammatory bowel disease. I. An unclassified Mycobacterium species isolated from patients with Crohn’s disease,” Digestive Diseases and Sciences, vol. 29, no. 12, pp. 1073–1079, 1984. View at Publisher · View at Google Scholar · View at Scopus
  134. E. Liverani, E. Scaioli, C. Cardamone, P. Dal Monte, and A. Belluzzi, “Mycobacterium avium subspecies paratuberculosis in the etiology of Crohn’s disease, cause or epiphenomenon?” World Journal of Gastroenterology, vol. 20, no. 36, pp. 13060–13070, 2014. View at Publisher · View at Google Scholar · View at Scopus
  135. G. P. Donaldson, S. M. Lee, and S. K. Mazmanian, “Gut biogeography of the bacterial microbiota,” Nature Reviews. Microbiology, vol. 14, no. 1, pp. 20–32, 2016. View at Publisher · View at Google Scholar · View at Scopus
  136. L. Sun, G. M. Nava, and T. S. Stappenbeck, “Host genetic susceptibility, dysbiosis, and viral triggers in inflammatory bowel disease,” Current Opinion in Gastroenterology, vol. 27, no. 4, pp. 321–327, 2011. View at Publisher · View at Google Scholar · View at Scopus
  137. E. K. Wright, M. A. Kamm, S. M. Teo, M. Inouye, J. Wagner, and C. D. Kirkwood, “Recent advances in characterizing the gastrointestinal microbiome in Crohn’s disease: a systematic review,” Inflammatory Bowel Diseases, vol. 21, no. 6, pp. 1219–1228, 2015. View at Publisher · View at Google Scholar · View at Scopus
  138. T. Irrazabal, A. Belcheva, S. E. Girardin, A. Martin, and D. J. Philpott, “The multifaceted role of the intestinal microbiota in colon cancer,” Molecular Cell, vol. 54, no. 2, pp. 309–320, 2014. View at Publisher · View at Google Scholar · View at Scopus
  139. D. Collins, A. M. Hogan, and D. C. Winter, “Microbial and viral pathogens in colorectal cancer,” The Lancet Oncology, vol. 12, no. 5, pp. 504–512, 2011. View at Publisher · View at Google Scholar · View at Scopus
  140. J. P. Nougayrede, S. Homburg, F. Taieb et al., “Escherichia coli induces DNA double-strand breaks in eukaryotic cells,” Science, vol. 313, no. 5788, pp. 848–851, 2006. View at Publisher · View at Google Scholar · View at Scopus
  141. O. Handa, Y. Naito, and T. Yoshikawa, “Helicobacter pylori: a ROS-inducing bacterial species in the stomach,” Inflammation Research, vol. 59, no. 12, pp. 997–1003, 2010. View at Publisher · View at Google Scholar · View at Scopus
  142. J. O. Lundberg, E. Weitzberg, J. A. Cole, and N. Benjamin, “Nitrate, bacteria and human health,” Nature Reviews. Microbiology, vol. 2, no. 7, pp. 593–602, 2004. View at Publisher · View at Google Scholar · View at Scopus
  143. O. D. Maddocks, K. M. Scanlon, and M. S. Donnenberg, “An Escherichia coli effector protein promotes host mutation via depletion of DNA mismatch repair proteins,” MBio, vol. 4, no. 3, article e00152-13, 2013. View at Publisher · View at Google Scholar · View at Scopus
  144. O. D. Maddocks, A. J. Short, M. S. Donnenberg, S. Bader, and D. J. Harrison, “Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans,” PloS One, vol. 4, no. 5, article e5517, 2009. View at Publisher · View at Google Scholar · View at Scopus
  145. S. Danese, M. Sans, and C. Fiocchi, “Inflammatory bowel disease: the role of environmental factors,” Autoimmunity Reviews, vol. 3, no. 5, pp. 394–400, 2004. View at Publisher · View at Google Scholar · View at Scopus
  146. H. S. de Souza and C. Fiocchi, “Immunopathogenesis of IBD: current state of the art,” Nature Reviews. Gastroenterology & Hepatology, vol. 13, no. 1, pp. 13–27, 2016. View at Publisher · View at Google Scholar · View at Scopus
  147. C. Manichanh, N. Borruel, F. Casellas, and F. Guarner, “The gut microbiota in IBD,” Nature Reviews. Gastroenterology & Hepatology, vol. 9, no. 10, pp. 599–608, 2012. View at Publisher · View at Google Scholar · View at Scopus
  148. M. D. Silverstein, B. A. Lashner, S. B. Hanauer, A. A. Evans, and J. B. Kirsner, “Cigarette smoking in Crohn’s disease,” The American Journal of Gastroenterology, vol. 84, no. 1, pp. 31–33, 1989. View at Google Scholar
  149. H. Mehta, K. Nazzal, and R. T. Sadikot, “Cigarette smoking and innate immunity,” Inflammation Research, vol. 57, no. 11, pp. 497–503, 2008. View at Publisher · View at Google Scholar · View at Scopus
  150. H. Wang, M. Yu, M. Ochani et al., “Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation,” Nature, vol. 421, no. 6921, pp. 384–388, 2003. View at Google Scholar
  151. R. Eliakim, F. Karmeli, P. Cohen, S. N. Heyman, and D. Rachmilewitz, “Dual effect of chronic nicotine administration: augmentation of jejunitis and amelioration of colitis induced by iodoacetamide in rats,” International Journal of Colorectal Disease, vol. 16, no. 1, pp. 14–21, 2001. View at Publisher · View at Google Scholar · View at Scopus
  152. X. Guo, J. K. Ko, Q. B. Mei, and C. H. Cho, “Aggravating effect of cigarette smoke exposure on experimental colitis is associated with leukotriene B(4) and reactive oxygen metabolites,” Digestion, vol. 63, no. 3, pp. 180–187, 2001. View at Publisher · View at Google Scholar
  153. X. Guo, W. P. Wang, J. K. Ko, and C. H. Cho, “Involvement of neutrophils and free radicals in the potentiating effects of passive cigarette smoking on inflammatory bowel disease in rats,” Gastroenterology, vol. 117, no. 4, pp. 884–892, 1999. View at Publisher · View at Google Scholar · View at Scopus
  154. M. I. Covas, P. Gambert, M. Fito, and R. de la Torre, “Wine and oxidative stress: up-to-date evidence of the effects of moderate wine consumption on oxidative damage in humans,” Atherosclerosis, vol. 208, no. 2, pp. 297–304, 2010. View at Publisher · View at Google Scholar · View at Scopus
  155. I. Rahman, S. K. Biswas, and P. A. Kirkham, “Regulation of inflammation and redox signaling by dietary polyphenols,” Biochemical Pharmacology, vol. 72, no. 11, pp. 1439–1452, 2006. View at Publisher · View at Google Scholar · View at Scopus
  156. F. Biasi, M. Astegiano, M. Maina, G. Leonarduzzi, and G. Poli, “Polyphenol supplementation as a complementary medicinal approach to treating inflammatory bowel disease,” Current Medicinal Chemistry, vol. 18, no. 31, pp. 4851–4865, 2011. View at Publisher · View at Google Scholar · View at Scopus
  157. E. Stermer, “Alcohol consumption and the gastrointestinal tract,” The Israel Medical Association Journal, vol. 4, no. 3, pp. 200–202, 2002. View at Google Scholar
  158. S. Siegmund, R. Spanagel, and M. V. Singer, “Role of the brain-gut axis in alcohol-related gastrointestinal diseases—what can we learn from new animal models?” Journal of Physiology and Pharmacology, vol. 54, Supplement 4, pp. 191–207, 2003. View at Google Scholar
  159. L. Andresen, V. L. Jorgensen, A. Perner, A. Hansen, J. Eugen-Olsen, and J. Rask-Madsen, “Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis,” Gut, vol. 54, no. 4, pp. 503–509, 2005. View at Publisher · View at Google Scholar · View at Scopus
  160. A. Visekruna, T. Joeris, D. Seidel et al., “Proteasome-mediated degradation of IkappaBalpha and processing of p105 in Crohn disease and ulcerative colitis,” The Journal of Clinical Investigation, vol. 116, no. 12, pp. 3195–3203, 2006. View at Publisher · View at Google Scholar · View at Scopus
  161. M. Pasparakis, “IKK/NF-kappaB signaling in intestinal epithelial cells controls immune homeostasis in the gut,” Mucosal Immunology, vol. 1, Supplement 1, pp. S54–S57, 2008. View at Publisher · View at Google Scholar · View at Scopus
  162. Y. Kuwano, K. Tominaga, T. Kawahara et al., “Tumor necrosis factor alpha activates transcription of the NADPH oxidase organizer 1 (NOXO1) gene and upregulates superoxide production in colon epithelial cells,” Free Radical Biology & Medicine, vol. 45, no. 12, pp. 1642–1652, 2008. View at Publisher · View at Google Scholar · View at Scopus
  163. W. Jeong, Y. Jung, H. Kim, S. J. Park, and S. G. Rhee, “Thioredoxin-related protein 14, a new member of the thioredoxin family with disulfide reductase activity: implication in the redox regulation of TNF-alpha signaling,” Free Radical Biology & Medicine, vol. 47, no. 9, pp. 1294–1303, 2009. View at Publisher · View at Google Scholar · View at Scopus
  164. Y. Naito, T. Takagi, T. Ishikawa et al., “Alpha-phenyl-N-tert-butylnitrone provides protection from dextran sulfate sodium-induced colitis in mice,” Antioxidants & Redox Signaling, vol. 4, no. 1, pp. 195–206, 2002. View at Publisher · View at Google Scholar · View at Scopus
  165. W. Qiu, B. Wu, X. Wang et al., “PUMA-mediated intestinal epithelial apoptosis contributes to ulcerative colitis in humans and mice,” The Journal of Clinical Investigation, vol. 121, no. 5, pp. 1722–1732, 2011. View at Publisher · View at Google Scholar · View at Scopus
  166. T. O. Khor, M. T. Huang, K. H. Kwon, J. Y. Chan, B. S. Reddy, and A. N. Kong, “Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis,” Cancer Research, vol. 66, no. 24, pp. 11580–11584, 2006. View at Publisher · View at Google Scholar · View at Scopus
  167. T. O. Khor, M. T. Huang, A. Prawan et al., “Increased susceptibility of Nrf2 knockout mice to colitis-associated colorectal cancer,” Cancer Prevention Research (Philadelphia, Pa.), vol. 1, no. 3, pp. 187–191, 2008. View at Publisher · View at Google Scholar · View at Scopus
  168. I. Stachel, C. Geismann, K. Aden et al., “Modulation of nuclear factor E2-related factor-2 (Nrf2) activation by the stress response gene immediate early response-3 (IER3) in colonic epithelial cells: a novel mechanism of cellular adaption to inflammatory stress,” The Journal of Biological Chemistry, vol. 289, no. 4, pp. 1917–1929, 2014. View at Publisher · View at Google Scholar · View at Scopus
  169. X. Kong, R. Thimmulappa, P. Kombairaju, and S. Biswal, “NADPH oxidase-dependent reactive oxygen species mediate amplified TLR4 signaling and sepsis-induced mortality in Nrf2-deficient mice,” Journal of Immunology, vol. 185, no. 1, pp. 569–577, 2010. View at Publisher · View at Google Scholar · View at Scopus
  170. F. Biasi, C. Mascia, M. Astegiano et al., “Pro-oxidant and proapoptotic effects of cholesterol oxidation products on human colonic epithelial cells: a potential mechanism of inflammatory bowel disease progression,” Free Radical Biology & Medicine, vol. 47, no. 12, pp. 1731–1741, 2009. View at Publisher · View at Google Scholar · View at Scopus
  171. C. Mascia, M. Maina, E. Chiarpotto, G. Leonarduzzi, G. Poli, and F. Biasi, “Proinflammatory effect of cholesterol and its oxidation products on CaCo-2 human enterocyte-like cells: effective protection by epigallocatechin-3-gallate,” Free Radical Biology & Medicine, vol. 49, no. 12, pp. 2049–2057, 2010. View at Publisher · View at Google Scholar · View at Scopus
  172. L. Kruidenier, I. Kuiper, W. Van Duijn et al., “Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease,” The Journal of Pathology, vol. 201, no. 1, pp. 17–27, 2003. View at Publisher · View at Google Scholar · View at Scopus
  173. L. Kruidenier, M. E. van Meeteren, I. Kuiper et al., “Attenuated mild colonic inflammation and improved survival from severe DSS-colitis of transgenic Cu/Zn-SOD mice,” Free Radical Biology & Medicine, vol. 34, no. 6, pp. 753–765, 2003. View at Publisher · View at Google Scholar · View at Scopus
  174. F. F. Chu, R. S. Esworthy, P. G. Chu et al., “Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes,” Cancer Research, vol. 64, no. 3, pp. 962–968, 2004. View at Publisher · View at Google Scholar · View at Scopus
  175. R. S. Esworthy, B. W. Kim, J. Chow, B. Shen, J. H. Doroshow, and F. F. Chu, “Nox1 causes ileocolitis in mice deficient in glutathione peroxidase-1 and -2,” Free Radical Biology & Medicine, vol. 68, pp. 315–325, 2014. View at Publisher · View at Google Scholar · View at Scopus
  176. A. Banning, S. Florian, S. Deubel et al., “GPx2 counteracts PGE2 production by dampening COX-2 and mPGES-1 expression in human colon cancer cells,” Antioxidants & Redox Signaling, vol. 10, no. 9, pp. 1491–1500, 2008. View at Publisher · View at Google Scholar · View at Scopus
  177. M. Nishikawa, N. Oshitani, T. Matsumoto, T. Nishigami, T. Arakawa, and M. Inoue, “Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis,” British Journal of Cancer, vol. 93, no. 3, pp. 331–337, 2005. View at Publisher · View at Google Scholar · View at Scopus
  178. A. Dashdorj, K. R. Jyothi, S. Lim et al., “Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines,” BMC Medicine, vol. 11, p. 178, 2013. View at Google Scholar
  179. Y. J. Lee, S. Y. Jeong, M. Karbowski, C. L. Smith, and R. J. Youle, “Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis,” Molecular Biology of the Cell, vol. 15, no. 11, pp. 5001–5011, 2004. View at Google Scholar
  180. A. Piechota-Polanczyk and J. Fichna, “Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 387, no. 7, pp. 605–620, 2014. View at Publisher · View at Google Scholar · View at Scopus
  181. L. Chouchana, C. Narjoz, P. Beaune, M. A. Loriot, and X. Roblin, “Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease,” Alimentary Pharmacology & Therapeutics, vol. 35, no. 1, pp. 15–36, 2012. View at Publisher · View at Google Scholar · View at Scopus
  182. K. J. Khan, M. C. Dubinsky, A. C. Ford, T. A. Ullman, N. J. Talley, and P. Moayyedi, “Efficacy of immunosuppressive therapy for inflammatory bowel disease: a systematic review and meta-analysis,” The American Journal of Gastroenterology, vol. 106, no. 4, pp. 630–642, 2011. View at Publisher · View at Google Scholar · View at Scopus
  183. N. Kannan and C. Guruvayoorappan, “Protective effect of Bauhinia tomentosa on acetic acid induced ulcerative colitis by regulating antioxidant and inflammatory mediators,” International Immunopharmacology, vol. 16, no. 1, pp. 57–66, 2013. View at Publisher · View at Google Scholar · View at Scopus
  184. H. Yanai, N. Salomon, and A. Lahat, “Complementary therapies in inflammatory bowel diseases,” Current Gastroenterology Reports, vol. 18, no. 12, p. 62, 2016. View at Google Scholar
  185. P. P. Trivedi and G. B. Jena, “Melatonin reduces ulcerative colitis-associated local and systemic damage in mice: investigation on possible mechanisms,” Digestive Diseases and Sciences, vol. 58, no. 12, pp. 3460–3474, 2013. View at Publisher · View at Google Scholar · View at Scopus
  186. L. J. Marnett, “The COXIB experience: a look in the rearview mirror,” Annual Review of Pharmacology and Toxicology, vol. 49, pp. 265–290, 2009. View at Publisher · View at Google Scholar · View at Scopus
  187. H. H. Arab, M. Y. Al-Shorbagy, D. M. Abdallah, and N. N. Nassar, “Telmisartan attenuates colon inflammation, oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease,” PloS One, vol. 9, no. 5, article e97193, 2014. View at Publisher · View at Google Scholar · View at Scopus
  188. R. A. Maheshwari, R. Balaraman, G. U. Sailor, and D. B. Sen, “Protective effect of simvastatin and rosuvastatin on trinitrobenzene sulfonic acid-induced colitis in rats,” Indian Journal of Pharmacology, vol. 47, no. 1, pp. 17–21, 2015. View at Publisher · View at Google Scholar · View at Scopus
  189. P. D. Terry, F. Villinger, G. A. Bubenik, and S. V. Sitaraman, “Melatonin and ulcerative colitis: evidence, biological mechanisms, and future research,” Inflammatory Bowel Diseases, vol. 15, no. 1, pp. 134–140, 2009. View at Publisher · View at Google Scholar · View at Scopus
  190. G. Paradies, G. Petrosillo, V. Paradies, R. J. Reiter, and F. M. Ruggiero, “Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease,” Journal of Pineal Research, vol. 48, no. 4, pp. 297–310, 2010. View at Publisher · View at Google Scholar · View at Scopus
  191. M. I. Pablos, M. T. Agapito, R. Gutierrez et al., “Melatonin stimulates the activity of the detoxifying enzyme glutathione peroxidase in several tissues of chicks,” Journal of Pineal Research, vol. 19, no. 3, pp. 111–115, 1995. View at Publisher · View at Google Scholar · View at Scopus
  192. C. Rodriguez, J. C. Mayo, R. M. Sainz et al., “Regulation of antioxidant enzymes: a significant role for melatonin,” Journal of Pineal Research, vol. 36, no. 1, pp. 1–9, 2004. View at Publisher · View at Google Scholar · View at Scopus
  193. G. Jena and P. P. Trivedi, “A review of the use of melatonin in ulcerative colitis: experimental evidence and new approaches,” Inflammatory Bowel Diseases, vol. 20, no. 3, pp. 553–563, 2014. View at Publisher · View at Google Scholar · View at Scopus
  194. V. Motilva, S. Garcia-Maurino, E. Talero, and M. Illanes, “New paradigms in chronic intestinal inflammation and colon cancer: role of melatonin,” Journal of Pineal Research, vol. 51, no. 1, pp. 44–60, 2011. View at Publisher · View at Google Scholar · View at Scopus
  195. C. Chojnacki, M. Wisniewska-Jarosinska, E. Walecka-Kapica, G. Klupinska, J. Jaworek, and J. Chojnacki, “Evaluation of melatonin effectiveness in the adjuvant treatment of ulcerative colitis,” Journal of Physiology and Pharmacology, vol. 62, no. 3, pp. 327–334, 2011. View at Google Scholar
  196. A. Siddiqui, H. Ancha, D. Tedesco, S. Lightfoot, C. A. Stewart, and R. F. Harty, “Antioxidant therapy with N-acetylcysteine plus mesalamine accelerates mucosal healing in a rodent model of colitis,” Digestive Diseases and Sciences, vol. 51, no. 4, pp. 698–705, 2006. View at Publisher · View at Google Scholar · View at Scopus
  197. L. G. Guijarro, J. Mate, J. P. Gisbert et al., “N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: randomized, placebo-controlled pilot study,” World Journal of Gastroenterology, vol. 14, no. 18, pp. 2851–2857, 2008. View at Publisher · View at Google Scholar · View at Scopus
  198. S. Kasperczyk, M. Dobrakowski, A. Kasperczyk, G. Machnik, and E. Birkner, “Effect of N-acetylcysteine administration on the expression and activities of antioxidant enzymes and the malondialdehyde level in the blood of lead-exposed workers,” Environmental Toxicology and Pharmacology, vol. 37, no. 2, pp. 638–647, 2014. View at Publisher · View at Google Scholar · View at Scopus
  199. J. J. Haddad, “Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive transcription factors,” Cellular Signalling, vol. 14, no. 11, pp. 879–897, 2002. View at Publisher · View at Google Scholar · View at Scopus
  200. I. Amrouche-Mekkioui and B. Djerdjouri, “N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice,” European Journal of Pharmacology, vol. 691, no. 1–3, pp. 209–217, 2012. View at Publisher · View at Google Scholar · View at Scopus
  201. A. S. Porfire, S. E. Leucuta, B. Kiss, F. Loghin, and A. E. Pârvu, “Investigation into the role of Cu/Zn-SOD delivery system on its antioxidant and antiinflammatory activity in rat model of peritonitis,” Pharmacological Reports, vol. 66, no. 4, pp. 670–676, 2014. View at Publisher · View at Google Scholar · View at Scopus
  202. C. L. Hou, J. Zhang, X. T. Liu, X. F. Zeng, and S. Y. Qiao, “Superoxide dismutase recombinant Lactobacillus fermentum ameliorates intestinal oxidative stress through inhibiting NF-kappaB activation in a trinitrobenzene sulphonic acid-induced colitis mouse model,” Journal of Applied Microbiology, vol. 116, no. 6, pp. 1621–1631, 2014. View at Publisher · View at Google Scholar · View at Scopus
  203. T. Ishihara, K. Tanaka, Y. Tasaka et al., “Therapeutic effect of lecithinized superoxide dismutase against colitis,” The Journal of Pharmacology and Experimental Therapeutics, vol. 328, no. 1, pp. 152–164, 2009. View at Google Scholar
  204. Y. Suzuki, T. Matsumoto, S. Okamoto, and T. Hibi, “A lecithinized superoxide dismutase (PC-SOD) improves ulcerative colitis,” Colorectal Disease, vol. 10, no. 9, pp. 931–934, 2008. View at Publisher · View at Google Scholar · View at Scopus
  205. T. L. Mikhailova, E. Sishkova, E. Poniewierka et al., “Randomised clinical trial: the efficacy and safety of propionyl-L-carnitine therapy in patients with ulcerative colitis receiving stable oral treatment,” Alimentary Pharmacology & Therapeutics, vol. 34, no. 9, pp. 1088–1097, 2011. View at Publisher · View at Google Scholar · View at Scopus
  206. M. G. Scioli, M. A. Stasi, D. Passeri et al., “Propionyl-L-carnitine is efficacious in ulcerative colitis through its action on the immune function and microvasculature,” Clinical and Translational Gastroenterology, vol. 5, article e55, 2014. View at Publisher · View at Google Scholar · View at Scopus
  207. B. Romier, Y. J. Schneider, Y. Larondelle, and A. During, “Dietary polyphenols can modulate the intestinal inflammatory response,” Nutrition Reviews, vol. 67, no. 7, pp. 363–378, 2009. View at Publisher · View at Google Scholar · View at Scopus
  208. A. Kaulmann and T. Bohn, “Bioactivity of polyphenols: preventive and adjuvant strategies toward reducing inflammatory bowel diseases-promises, perspectives, and pitfalls,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 9346470, 2016. View at Publisher · View at Google Scholar · View at Scopus
  209. M. Chiba, T. Abe, H. Tsuda, H. Tozawa, K. Fujiwara, and H. Imai, “Lifestyle-related disease in Crohn’s disease: relapse prevention by a semi-vegetarian diet,” World Journal of Gastroenterology, vol. 16, no. 20, pp. 2484–2495, 2010. View at Publisher · View at Google Scholar · View at Scopus
  210. T. Vezza, A. Rodriguez-Nogales, F. Algieri, M. P. Utrilla, M. E. Rodriguez-Cabezas, and J. Galvez, “Flavonoids in inflammatory bowel disease: a review,” Nutrients, vol. 8, no. 4, p. 211, 2016. View at Publisher · View at Google Scholar · View at Scopus
  211. H. R. Sodagari, M. H. Farzaei, R. Bahramsoltani, A. H. Abdolghaffari, M. Mahmoudi, and N. Rezaei, “Dietary anthocyanins as a complementary medicinal approach for management of inflammatory bowel disease,” Expert Review of Gastroenterology & Hepatology, vol. 9, no. 6, pp. 807–820, 2015. View at Publisher · View at Google Scholar · View at Scopus
  212. J. Epstein, I. R. Sanderson, and T. T. Macdonald, “Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies,” The British Journal of Nutrition, vol. 103, no. 11, pp. 1545–1557, 2010. View at Publisher · View at Google Scholar · View at Scopus
  213. Y. He, Y. Yue, X. Zheng, K. Zhang, S. Chen, and Z. Du, “Curcumin, inflammation, and chronic diseases: how are they linked?” Molecules, vol. 20, no. 5, pp. 9183–9213, 2015. View at Publisher · View at Google Scholar · View at Scopus
  214. A. Anthwal, B. K. Thakur, M. S. Rawat, D. S. Rawat, A. K. Tyagi, and B. B. Aggarwal, “Synthesis, characterization and in vitro anticancer activity of C-5 curcumin analogues with potential to inhibit TNF-alpha-induced NF-kappaB activation,” BioMed Research International, vol. 2014, Article ID 524161, 2014. View at Publisher · View at Google Scholar · View at Scopus
  215. N. S. Chang, N. Joki, J. Mattison, T. Dinh, and S. John, “Characterization of serum adhesive proteins that block tumor necrosis factor-mediated cell death,” Cell Death and Differentiation, vol. 4, no. 8, pp. 779–786, 1997. View at Publisher · View at Google Scholar
  216. S. C. Gupta, A. K. Tyagi, P. Deshmukh-Taskar, M. Hinojosa, S. Prasad, and B. B. Aggarwal, “Downregulation of tumor necrosis factor and other proinflammatory biomarkers by polyphenols,” Archives of Biochemistry and Biophysics, vol. 559, pp. 91–99, 2014. View at Publisher · View at Google Scholar · View at Scopus
  217. Y. Topcu-Tarladacalisir, M. Akpolat, Y. H. Uz et al., “Effects of curcumin on apoptosis and oxidoinflammatory regulation in a rat model of acetic acid-induced colitis: the roles of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase,” Journal of Medicinal Food, vol. 16, no. 4, pp. 296–305, 2013. View at Publisher · View at Google Scholar · View at Scopus
  218. R. A. Taylor and M. C. Leonard, “Curcumin for inflammatory bowel disease: a review of human studies,” Alternative Medicine Review, vol. 16, no. 2, pp. 152–156, 2011. View at Google Scholar
  219. M. S. Baliga, N. Joseph, M. V. Venkataranganna, A. Saxena, V. Ponemone, and R. Fayad, “Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations,” Food & Function, vol. 3, no. 11, pp. 1109–1117, 2012. View at Publisher · View at Google Scholar · View at Scopus
  220. H. Hanai, T. Iida, K. Takeuchi et al., “Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial,” Clinical Gastroenterology and Hepatology, vol. 4, no. 12, pp. 1502–1506, 2006. View at Publisher · View at Google Scholar · View at Scopus
  221. K. Sugimoto, H. Hanai, K. Tozawa et al., “Curcumin prevents and ameliorates trinitrobenzene sulfonic acid-induced colitis in mice,” Gastroenterology, vol. 123, no. 6, pp. 1912–1922, 2002. View at Publisher · View at Google Scholar · View at Scopus
  222. J. K. Triantafillidis, A. Triantafyllidi, C. Vagianos, and A. Papalois, “Favorable results from the use of herbal and plant products in inflammatory bowel disease: evidence from experimental animal studies,” Annals of Gastroenterology, vol. 29, no. 3, pp. 268–281, 2016. View at Publisher · View at Google Scholar · View at Scopus
  223. N. Schweigert, A. J. Zehnder, and R. I. Eggen, “Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals,” Environmental Microbiology, vol. 3, no. 2, pp. 81–91, 2001. View at Publisher · View at Google Scholar · View at Scopus
  224. M. J. Carter, A. J. Lobo, and S. P. Travis, “Guidelines for the management of inflammatory bowel disease in adults,” Gut, vol. 53, Supplement 5, pp. V1–16, 2004. View at Google Scholar
  225. A. Kornbluth, D. B. Sachar, and Practice Parameters Committee of the American College of Gastroenterology, “Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee,” The American Journal of Gastroenterology, vol. 105, no. 3, pp. 501–523, 2010, quiz 524. View at Publisher · View at Google Scholar · View at Scopus
  226. H. H. Arab, S. A. Salama, A. H. Eid, H. A. Omar, E. S. Arafa, and I. A. Maghrabi, “Camel’s milk ameliorates TNBS-induced colitis in rats via downregulation of inflammatory cytokines and oxidative stress,” Food and Chemical Toxicology, vol. 69, pp. 294–302, 2014. View at Publisher · View at Google Scholar · View at Scopus
  227. M. J. Oliveras-Lopez, G. Berna, E. M. Carneiro, H. L. de la Serrana, F. Martín, and M. C. López, “An extra-virgin olive oil rich in polyphenolic compounds has antioxidant effects in OF1 mice,” The Journal of Nutrition, vol. 138, no. 6, pp. 1074–1078, 2008. View at Google Scholar
  228. R. W. Owen, R. Haubner, G. Wurtele, W. E. Hull, B. Spiegelhalder, and H. Bartsch, “Olives and olive oil in cancer prevention,” European Journal of Cancer Prevention, vol. 13, no. 4, pp. 319–326, 2004. View at Publisher · View at Google Scholar · View at Scopus
  229. M. Bitiren, A. Z. Karakilcik, M. Zerin et al., “Protective effects of selenium and vitamin E combination on experimental colitis in blood plasma and colon of rats,” Biological Trace Element Research, vol. 136, no. 1, pp. 87–95, 2010. View at Publisher · View at Google Scholar · View at Scopus
  230. N. D'Orazio, M. A. Gammone, E. Gemello, M. De Girolamo, S. Cusenza, and G. Riccioni, “Marine bioactives: pharmacological properties and potential applications against inflammatory diseases,” Marine Drugs, vol. 10, no. 4, pp. 812–833, 2012. View at Publisher · View at Google Scholar · View at Scopus
  231. C. W. Barrett, S. P. Short, and C. S. Williams, “Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut,” Cellular and Molecular Life Sciences, vol. 74, 2016. View at Google Scholar
  232. C. W. Barrett, K. Singh, A. K. Motley et al., “Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis,” PloS One, vol. 8, no. 7, article e67845, 2013. View at Publisher · View at Google Scholar · View at Scopus
  233. S. M. Barbalho, A. Goulart Rde, K. Quesada, M. D. Bechara, and A. D. de Carvalho, “Inflammatory bowel disease: can omega-3 fatty acids really help?” Annals of Gastroenterology, vol. 29, no. 1, pp. 37–43, 2016. View at Google Scholar
  234. H. Zhang, C. A. Hu, J. Kovacs-Nolan, and Y. Mine, “Bioactive dietary peptides and amino acids in inflammatory bowel disease,” Amino Acids, vol. 47, no. 10, pp. 2127–2141, 2015. View at Publisher · View at Google Scholar · View at Scopus
  235. N. Sengul, S. Isik, B. Aslim, G. Uçar, and A. E. Demirbağ, “The effect of exopolysaccharide-producing probiotic strains on gut oxidative damage in experimental colitis,” Digestive Diseases and Sciences, vol. 56, no. 3, pp. 707–714, 2011. View at Publisher · View at Google Scholar · View at Scopus
  236. L. Zhong, X. Zhang, and M. Covasa, “Emerging roles of lactic acid bacteria in protection against colorectal cancer,” World Journal of Gastroenterology, vol. 20, no. 24, pp. 7878–7886, 2014. View at Publisher · View at Google Scholar · View at Scopus
  237. A. Amaretti, M. di Nunzio, A. Pompei, S. Raimondi, M. Rossi, and A. Bordoni, “Antioxidant properties of potentially probiotic bacteria: in vitro and in vivo activities,” Applied Microbiology and Biotechnology, vol. 97, no. 2, pp. 809–817, 2013. View at Publisher · View at Google Scholar · View at Scopus
  238. E. Songisepp, J. Kals, T. Kullisaar et al., “Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers,” Nutrition Journal, vol. 4, p. 22, 2005. View at Google Scholar
  239. D. Haller, J. M. Antoine, S. Bengmark, P. Enck, G. T. Rijkers, and I. Lenoir-Wijnkoop, “Guidance for substantiating the evidence for beneficial effects of probiotics: probiotics in chronic inflammatory bowel disease and the functional disorder irritable bowel syndrome,” The Journal of Nutrition, vol. 140, no. 3, pp. 690S–697S, 2010. View at Publisher · View at Google Scholar · View at Scopus
  240. D. Jonkers, J. Penders, A. Masclee, and M. Pierik, “Probiotics in the management of inflammatory bowel disease: a systematic review of intervention studies in adult patients,” Drugs, vol. 72, no. 6, pp. 803–823, 2012. View at Publisher · View at Google Scholar · View at Scopus
  241. K. Biswas, U. Bandyopadhyay, I. Chattopadhyay, A. Varadaraj, E. Ali, and R. K. Banerjee, “A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical,” The Journal of Biological Chemistry, vol. 278, no. 13, pp. 10993–11001, 2003. View at Publisher · View at Google Scholar · View at Scopus
  242. M. R. Mazalli and N. Bragagnolo, “Increase of cholesterol oxidation and decrease of PUFA as a result of thermal processing and storage in eggs enriched with n-3 fatty acids,” Journal of Agricultural and Food Chemistry, vol. 57, no. 11, pp. 5028–5034, 2009. View at Publisher · View at Google Scholar · View at Scopus
  243. D. A. Parks, “Oxygen radicals: mediators of gastrointestinal pathophysiology,” Gut, vol. 30, no. 3, pp. 293–298, 1989. View at Publisher · View at Google Scholar
  244. I. S. Young and J. V. Woodside, “Antioxidants in health and disease,” Journal of Clinical Pathology, vol. 54, no. 3, pp. 176–186, 2001. View at Publisher · View at Google Scholar · View at Scopus
  245. F. Borrelli, I. Fasolino, B. Romano et al., “Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease,” Biochemical Pharmacology, vol. 85, no. 9, pp. 1306–1316, 2013. View at Publisher · View at Google Scholar · View at Scopus
  246. M. Herulf, T. Ljung, P. M. Hellstrom, E. Weitzberg, and J. O. Lundberg, “Increased luminal nitric oxide in inflammatory bowel disease as shown with a novel minimally invasive method,” Scandinavian Journal of Gastroenterology, vol. 33, no. 2, pp. 164–169, 1998. View at Google Scholar
  247. S. J. McKenzie, M. S. Baker, G. D. Buffinton, and W. F. Doe, “Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease,” The Journal of Clinical Investigation, vol. 98, no. 1, pp. 136–141, 1996. View at Publisher · View at Google Scholar
  248. C. J. Schorah, “Antioxidants in children with inflammatory bowel disease,” The American Journal of Clinical Nutrition, vol. 67, no. 1, pp. 151-152, 1998. View at Google Scholar
  249. B. Sido, V. Hack, A. Hochlehnert, H. Lipps, C. Herfarth, and W. Dröge, “Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease,” Gut, vol. 42, no. 4, pp. 485–492, 1998. View at Publisher · View at Google Scholar