Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 7369671, 15 pages
https://doi.org/10.1155/2017/7369671
Research Article

Commiphora molmol Modulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1 Pathways and Attenuates Oxidative Stress and Hematological Alterations in Hyperammonemic Rats

1Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef, Egypt
2Department of Endocrinology, Diabetes & Nutrition, Charité-University Medicine Berlin, Germany
3College of Medicine, King Saud Bin Abdulaziz University for Health Science (KSAU-HS), Riyadh, Saudi Arabia
4King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
5Biology Department, Faculty of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
6Biology Department, Faculty of Science, Aljouf University, Sakakah, Aljouf, Saudi Arabia
7Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
8School of Earth and Environmental Sciences & Research Institute of Oceanography, Seoul National University, Seoul, Republic of Korea
9School of Healthcare Science, Manchester Metropolitan University, Manchester, UK
10Zoology Department, Faculty of Science, Beni-Suef University, Beni Suef, Egypt

Correspondence should be addressed to Ayman M. Mahmoud; ge.ude.usb.ecneics@duomham.namya

Received 1 March 2017; Revised 21 May 2017; Accepted 28 May 2017; Published 28 June 2017

Academic Editor: Tiziana Persichini

Copyright © 2017 Ayman M. Mahmoud 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. S. M. Riordan and R. Williams, “Treatment of hepatic encephalopathy,” The New England Journal of Medicine, vol. 337, no. 7, pp. 473–479, 1997. View at Publisher · View at Google Scholar · View at Scopus
  2. J. P. Sturgeon and D. L. Shawcross, “Recent insights into the pathogenesis of hepatic encephalopathy and treatments,” Expert Review of Gastroenterology & Hepatology, vol. 8, no. 1, pp. 83–100, 2014. View at Google Scholar
  3. F. F. Poordad, “Review article: the burden of hepatic encephalopathy,” Alimentary Pharmacology & Therapeutics, vol. 25, Supplement 1, pp. 3–9, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Romero-Gomez, S. Montagnese, and R. Jalan, “Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure,” Journal of Hepatology, vol. 62, no. 2, pp. 437–447, 2015. View at Publisher · View at Google Scholar
  5. J. Albrecht and M. D. Norenberg, “Glutamine: a Trojan horse in ammonia neurotoxicity,” Hepatology, vol. 44, no. 4, pp. 788–794, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. W. Bernal, C. Hall, C. J. Karvellas, G. Auzinger, E. Sizer, and J. Wendon, “Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure,” Hepatology, vol. 46, no. 6, pp. 1844–1852, 2007. View at Publisher · View at Google Scholar · View at Scopus
  7. M. C. Machado and F. Pinheiro da Silva, “Hyperammonemia due to urea cycle disorders: a potentially fatal condition in the intensive care setting,” Journal of Intensive Care, vol. 2, no. 1, p. 22, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. M. K. Chung, D. O. Martin, D. Sprecher et al., “C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation,” Circulation, vol. 104, no. 24, pp. 2886–2891, 2001. View at Publisher · View at Google Scholar
  9. M. D. Norenberg, A. R. Jayakumar, and K. V. Rama Rao, “Oxidative stress in the pathogenesis of hepatic encephalopathy,” Metabolic Brain Disease, vol. 19, no. 3-4, pp. 313–329, 2004. View at Google Scholar
  10. A. M. Mahmoud, “Influence of rutin on biochemical alterations in hyperammonemia in rats,” Experimental and Toxicologic Pathology, vol. 64, no. 7-8, pp. 783–789, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. A. M. Mahmoud, M. O. Germoush, and A. S. Soliman, “Ruta graveolens mitigates ammonium chloride-induced hyperammonemia by modulating antioxidant status and pro-inflammatory cytokines,” Life Science Journal, vol. 11, no. 6, pp. 269–275, 2014. View at Google Scholar
  12. E. Kosenko, Y. Kaminsky, I. G. Stavroskaya, and V. Felipo, “Alteration of mitochondrial calcium homeostasis by ammonia-induced activation of NMDA receptors in rat brain in vivo,” Brain Research, vol. 880, no. 1-2, pp. 139–146, 2000. View at Publisher · View at Google Scholar · View at Scopus
  13. M. D. Minana, R. Corbalan, C. Montoliu, C. M. Teng, and V. Felipo, “Chronic hyperammonemia in rats impairs activation of soluble guanylate cyclase in neurons and in lymphocytes: a putative peripheral marker for neurological alterations,” Biochemical and Biophysical Research Communications, vol. 257, no. 2, pp. 405–409, 1999. View at Publisher · View at Google Scholar · View at Scopus
  14. M. D. Munoz, P. Monfort, J. M. Gaztelu, and V. Felipo, “Hyperammonemia impairs NMDA receptor-dependent long-term potentiation in the CA1 of rat hippocampus in vitro,” Neurochemical Research, vol. 25, no. 4, pp. 437–441, 2000. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Lopez-Alarcon and A. Denicola, “Evaluating the antioxidant capacity of natural products: a review on chemical and cellular-based assays,” Analytica Chimica Acta, vol. 763, pp. 1–10, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. A. Ramakrishnan, N. Vijayakumar, and M. Renuka, “Naringin regulates glutamate-nitric oxide cGMP pathway in ammonium chloride induced neurotoxicity,” Biomedicine & Pharmacotherapy, vol. 84, pp. 1717–1726, 2016. View at Publisher · View at Google Scholar · View at Scopus
  17. M. J. Calkins, R. J. Jakel, D. A. Johnson, K. Chan, Y. W. Kan, and J. A. Johnson, “Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 1, pp. 244–249, 2005. View at Google Scholar
  18. A. Y. Shih, P. Li, and T. H. Murphy, “A small-molecule-inducible Nrf2-mediated antioxidant response provides effective prophylaxis against cerebral ischemia in vivo,” The Journal of Neuroscience, vol. 25, no. 44, pp. 10321–10335, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. T. Satoh, K. Kosaka, K. Itoh et al., “Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1,” Journal of Neurochemistry, vol. 104, no. 4, pp. 1116–1131, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Yang, X. Zhang, H. Fan, and Y. Liu, “Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia,” Brain Research, vol. 1282, pp. 133–141, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. K. Itoh, T. Chiba, S. Takahashi et al., “An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements,” Biochemical and Biophysical Research Communications, vol. 236, no. 2, pp. 313–322, 1997. View at Google Scholar
  22. P. Monfort, M. D. Munoz, A. ElAyadi, E. Kosenko, and V. Felipo, “Effects of hyperammonemia and liver failure on glutamatergic neurotransmission,” Metabolic Brain Disease, vol. 17, no. 4, pp. 237–250, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. C. Hermenegildo, P. Monfort, and V. Felipo, “Activation of N-methyl-D-aspartate receptors in rat brain in vivo following acute ammonia intoxication: characterization by in vivo brain microdialysis,” Hepatology, vol. 31, no. 3, pp. 709–715, 2000. View at Publisher · View at Google Scholar
  24. C. Montoliu, M. Llansola, P. Monfort et al., “Role of nitric oxide and cyclic GMP in glutamate-induced neuronal death,” Neurotoxicity Research, vol. 3, no. 2, pp. 179–188, 2001. View at Publisher · View at Google Scholar
  25. C. A. Ribeiro, F. H. Hickmann, and M. Wajner, “Neurochemical evidence that 3-methylglutaric acid inhibits synaptic Na+,K+−ATPase activity probably through oxidative damage in brain cortex of young rats,” International Journal of Developmental Neuroscience, vol. 29, no. 1, pp. 1–7, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Renuka, N. Vijayakumar, and A. Ramakrishnan, “Chrysin, a flavonoid attenuates histological changes of hyperammonemic rats: a dose dependent study,” Biomedicine & Pharmacotherapy, vol. 82, pp. 345–354, 2016. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Gonzalez-Usano, O. Cauli, A. Agusti, and V. Felipo, “Pregnenolone sulfate restores the glutamate-nitric-oxide-cGMP pathway and extracellular GABA in cerebellum and learning and motor coordination in hyperammonemic rats,” ACS Chemical Neuroscience, vol. 5, no. 2, pp. 100–105, 2014. View at Publisher · View at Google Scholar · View at Scopus
  28. L. O. Hanus, T. Rezanka, V. M. Dembitsky, and A. Moussaieff, “Myrrh—Commiphora chemistry,” Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czech Republic, vol. 149, no. 1, pp. 3–27, 2005. View at Publisher · View at Google Scholar
  29. M. M. Rahman, M. Garvey, L. J. Piddock, and S. Gibbons, “Antibacterial terpenes from the oleo-resin of Commiphora molmol (Engl.),” Phytotherapy Research, vol. 22, no. 10, pp. 1356–1360, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. A. Salama, W. Ibrahim, T. El-Nimr, M. A. Abd El, and E. Tousson, “Effect of myrrh extract (Mirazid®) on experimentally diabetic rats,” Pharmacologia Pharmacologia, vol. 5, no. 4, pp. 135–142, 2014. View at Google Scholar
  31. D. A. Tipton, B. Lyle, H. Babich, and M. Dabbous, “In vitro cytotoxic and anti-inflammatory effects of myrrh oil on human gingival fibroblasts and epithelial cells,” Toxicology In Vitro, vol. 17, no. 3, pp. 301–310, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. K. M. Ashry, Y. S. El-Sayed, R. M. Khamiss, and I. M. El-Ashmawy, “Oxidative stress and immunotoxic effects of lead and their amelioration with myrrh (Commiphora molmol) emulsion,” Food and Chemical Toxicology, vol. 48, no. 1, pp. 236–241, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. M. El-Shahat, S. El-Abd, M. Alkafafy, and G. El-Khatib, “Potential chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis in rats: myrrh (Commiphora molmol) vs. turmeric (Curcuma longa),” Acta Histochemica, vol. 114, no. 5, pp. 421–428, 2012. View at Publisher · View at Google Scholar · View at Scopus
  34. E. M. Kamel, A. M. Mahmoud, S. A. Ahmed, and A. M. Lamsabhi, “A phytochemical and computational study on flavonoids isolated from Trifolium resupinatum L. and their novel hepatoprotective activity,” Food & Function, vol. 7, no. 4, pp. 2094–2106, 2016. View at Publisher · View at Google Scholar · View at Scopus
  35. M. A. Shalaby and A. A. Hammouda, “Analgesic, anti-inflammatory and anti-hyperlipidemic activities of Commiphora molmol extract (myrrh),” Journal of Intercultural Ethnopharmacology, vol. 3, no. 2, pp. 56–62, 2014. View at Publisher · View at Google Scholar
  36. F. da Fonseca-Wollheim, “Preanalytical increase of ammonia in blood specimens from healthy subjects,” Clinical Chemistry, vol. 36, Part 1, no. 8, pp. 1483–1487, 1990. View at Google Scholar
  37. G. Schumann and R. Klauke, “New IFCC reference procedures for the determination of catalytic activity concentrations of five enzymes in serum: preliminary upper reference limits obtained in hospitalized subjects,” Clinica Chimica Acta, vol. 327, no. 1-2, pp. 69–79, 2003. View at Google Scholar
  38. C. Wenger, A. Kaplan, F. F. Rubaltelli, and C. Hammerman, “Alkaline phosphatase,” in Clinical Chemistry, pp. 1094–1098, The C. V. Mosby Co, St. Louis, MO, USA, 1984. View at Google Scholar
  39. H. G. Preuss, S. T. Jarrell, R. Scheckenbach, S. Lieberman, and R. A. Anderson, “Comparative effects of chromium, vanadium and Gymnema sylvestre on sugar-induced blood pressure elevations in SHR,” Journal of the American College of Nutrition, vol. 17, no. 2, pp. 116–123, 1998. View at Publisher · View at Google Scholar
  40. E. Beutler, O. Duron, and B. M. Kelly, “Improved method for the determination of blood glutathione,” The Journal of Laboratory and Clinical Medicine, vol. 61, pp. 882–888, 1963. View at Google Scholar
  41. S. Marklund and G. Marklund, “Involvement of the superoxide anion radical in the autoxidation of Pyrogallol and a convenient assay for superoxide dismutase,” FEBS European Journal of Biochemistry, vol. 47, no. 3, pp. 469–474, 1974. View at Publisher · View at Google Scholar · View at Scopus
  42. G. Cohen, D. Dembiec, and J. Marcus, “Measurement of catalase activity in tissue extracts,” Analytical Biochemistry Analytical Biochemistry, vol. 34, no. 1, pp. 30–38, 1970. View at Publisher · View at Google Scholar · View at Scopus
  43. B. Matkovics, L. Szabo, and I. S. Varga, “Determination of enzyme activities in lipid peroxidation and glutathione pathways (in Hungarian),” Laboratoriumi Diagnosztika, vol. 15, pp. 248-249, 1998. View at Google Scholar
  44. P. Lund, “L-glutamine and L-glutamate: UV method with glutaminase and glutamate dehydrogenase,” in Methods in Enzymatic Analysis, H. U. Bergmeyer, Ed., pp. 357–363, VCH, Verlagsgesellschaft, Weinheim, Germany, 1986. View at Google Scholar
  45. H. Rauchova, Z. Drahota, and J. Koudelova, “The role of membrane fluidity changes and thiobarbituric acid-reactive substances production in the inhibition of cerebral cortex Na+/K+−ATPase activity,” Physiological Research, vol. 48, no. 1, pp. 73–78, 1999. View at Google Scholar
  46. C. Fiske and Y. Subbarow, “The colourimetric determination of phosphorus,” Journal of Biological Chemistry, vol. 66, pp. 375–400, 1925. View at Google Scholar
  47. A. M. Mahmoud, “Hematological alterations in diabetic rats - role of adipocytokines and effect of citrus flavonoids,” EXCLI Journal, vol. 12, pp. 647–657, 2013. View at Google Scholar
  48. A. M. Mahmoud, M. O. Germoush, M. F. Alotaibi, and O. E. Hussein, “Possible involvement of Nrf2 and PPARgamma up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity,” Biomedicine & Pharmacotherapy, vol. 86, pp. 297–306, 2017. View at Publisher · View at Google Scholar
  49. M. M. Bradford, “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding,” Analytical Biochemistry, vol. 72, pp. 248–254, 1976. View at Publisher · View at Google Scholar · View at Scopus
  50. S. K. Ramaiah, “A toxicologist guide to the diagnostic interpretation of hepatic biochemical parameters,” Food and Chemical Toxicology, vol. 45, no. 9, pp. 1551–1557, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. S. S. Al-Rejaie, “Effect of oleo-gum-resin on ethanol-induced hepatotoxicity in rats,” Journal of Medical Sciences (Faisalabad), vol. 12, no. 1, pp. 1–9, 2012. View at Google Scholar
  52. A. A. Alm-Eldeen, S. A. El-Naggar, K. F. El-Boray, H. A. Elgebaly, and I. H. Osman, “Protective role of commiphora molmol extract against liver and kidney toxicity induced by carbon tetrachloride in mice,” Tropical Journal of Pharmaceutical Research, vol. 15, no. 1, pp. 65–72, 2016. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Ahmad, M. Raish, M. A. Ganaie et al., “Hepatoprotective effect of Commiphora myrrha against d-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes,” Pharmaceutical Biology, vol. 53, no. 12, pp. 1759–1767, 2015. View at Publisher · View at Google Scholar · View at Scopus
  54. A. M. Mahmoud, A. R. Zaki, M. E. Hassan, and G. Mostafa-Hedeab, “Commiphora molmol resin attenuates diethylnitrosamine/phenobarbital-induced hepatocarcinogenesis by modulating oxidative stress, inflammation, angiogenesis and Nrf2/ARE/HO-1 signaling,” Chemico-Biological Interactions, vol. 270, pp. 41–50, 2017. View at Publisher · View at Google Scholar
  55. M. D. Minana, V. Felipo, R. Wallace, and S. Grisolia, “Hyperammonemia decreases body fat content in rat,” FEBS Letters, vol. 249, no. 2, pp. 261–263, 1989. View at Publisher · View at Google Scholar · View at Scopus
  56. D. Shawcross and R. Jalan, “The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation,” Cellular and Molecular Life Sciences, vol. 62, no. 19-20, pp. 2295–2304, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. D. L. Shawcross, G. Wright, S. W. Olde Damink, and R. Jalan, “Role of ammonia and inflammation in minimal hepatic encephalopathy,” Metabolic Brain Disease, vol. 22, no. 1, pp. 125–138, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. D. L. Shawcross, G. A. Wright, V. Stadlbauer et al., “Ammonia impairs neutrophil phagocytic function in liver disease,” Hepatology, vol. 48, no. 4, pp. 1202–1212, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Odeh, E. Sabo, I. Srugo, and A. Oliven, “Serum levels of tumor necrosis factor-alpha correlate with severity of hepatic encephalopathy due to chronic liver failure,” Liver International, vol. 24, no. 2, pp. 110–116, 2004. View at Publisher · View at Google Scholar
  60. M. Odeh, E. Sabo, I. Srugo, and A. Oliven, “Relationship between tumor necrosis factor-alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure,” Annals of Medicine, vol. 37, no. 8, pp. 603–612, 2005. View at Google Scholar
  61. D. L. Shawcross, N. A. Davies, R. Williams, and R. Jalan, “Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis,” Journal of Hepatology, vol. 40, no. 2, pp. 247–254, 2004. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Chung, J. Gottstein, and A. T. Blei, “Indomethacin prevents the development of experimental ammonia-induced brain edema in rats after portacaval anastomosis,” Hepatology, vol. 34, no. 2, pp. 249–254, 2001. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Su, Y. Hua, Y. Wang et al., “Evaluation of the anti-inflammatory and analgesic properties of individual and combined extracts from Commiphora myrrha, and Boswellia carterii,” Journal of Ethnopharmacology, vol. 139, no. 2, pp. 649–656, 2012. View at Publisher · View at Google Scholar · View at Scopus
  64. A. J. Fatani, F. S. Alrojayee, M. Y. Parmar, H. M. Abuohashish, M. M. Ahmed, and S. S. Al-Rejaie, “Myrrh attenuates oxidative and inflammatory processes in acetic acid-induced ulcerative colitis,” Experimental and Therapeutic Medicine, vol. 12, no. 2, pp. 730–738, 2016. View at Publisher · View at Google Scholar · View at Scopus
  65. K. B. Dakshayani, S. Velvizhi, and P. Subramanian, “Effects of ornithine alpha-ketoglutarate on circulatory antioxidants and lipid peroxidation products in ammonium acetate treated rats,” Annals of Nutrition & Metabolism, vol. 46, no. 3-4, pp. 93–96, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. O. Kharoubi, M. Slimani, A. Aoues, and L. Seddik, “Prophylactic effects of wormwood on lipid peroxidation in an animal model of lead intoxication,” Indian Journal of Nephrology, vol. 18, no. 2, pp. 51–57, 2008. View at Publisher · View at Google Scholar
  67. A. Chevallier, The Encyclopedia of Medicinal Plants, 1996.
  68. S. L. Su, J. A. Duan, Y. P. Tang et al., “Isolation and biological activities of neomyrrhaol and other terpenes from the resin of Commiphora myrrha,” Planta Medica, vol. 75, no. 4, pp. 351–355, 2009. View at Google Scholar
  69. M. Mahboubi and N. Kazempour, “The antimicrobial and antioxidant activities of Commiphora molmol extracts,” Biharean Biologist, vol. 10, no. 2, pp. 131–133, 2016. View at Google Scholar
  70. A. M. Mahmoud, “Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARgamma and abrogation of oxidative stress and inflammation,” Canadian Journal of Physiology and Pharmacology, vol. 92, no. 9, pp. 717–724, 2014. View at Publisher · View at Google Scholar · View at Scopus
  71. A. M. Mahmoud, M. B. Ashour, A. Abdel-Moneim, and O. M. Ahmed, “Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat fed/streptozotocin-induced type 2 diabetic rats,” Journal of Diabetes and its Complications, vol. 26, no. 6, pp. 483–490, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. A. M. Mahmoud and H. S. Al Dera, “18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation,” Genes & Nutrition, vol. 10, no. 6, pp. 1–13, 2015. View at Publisher · View at Google Scholar · View at Scopus
  73. S. M. Abd El-Twab, W. G. Hozayen, O. E. Hussein, and A. M. Mahmoud, “18beta-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants,” Renal Failure, vol. 8, pp. 1–12, 2016. View at Google Scholar
  74. A. M. Mahmoud, F. L. Wilkinson, A. M. Jones et al., “A novel role for small molecule glycomimetics in the protection against lipid-induced endothelial dysfunction: involvement of Akt/eNOS and Nrf2/ARE signaling,” Biochimica et Biophysica Acta, vol. 1861, no. 1, Part A, pp. 3311–3322, 2017. View at Publisher · View at Google Scholar
  75. S. S. Boyanapalli, X. Paredes-Gonzalez, F. Fuentes et al., “Nrf2 knockout attenuates the anti-inflammatory effects of phenethyl isothiocyanate and curcumin,” Chemical Research in Toxicology, vol. 27, no. 12, pp. 2036–2043, 2014. View at Publisher · View at Google Scholar · View at Scopus
  76. E. H. Kobayashi, T. Suzuki, R. Funayama et al., “Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription,” Nature Communications, vol. 7, p. 11624, 2016. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Alya, D. B. Ines, L. Montassar, G. Najoua, and E. F. Saloua, “Oxidative stress, biochemical alterations, and hyperlipidemia in female rats induced by lead chronic toxicity during puberty and post puberty periods,” Iranian Journal of Basic Medical Sciences, vol. 18, no. 10, pp. 1034–1043, 2015. View at Google Scholar
  78. H. Aggarwal, U. A. Rao, S. Singla, and G. Dabas, “A study on hematological spectrum in patients with alcoholic liver cirrhosis,” Journal of Clinical and Experimental Hepatology, vol. 5, Supplement 2, pp. S18–S19, 2015. View at Publisher · View at Google Scholar
  79. E. Kalaitzakis, A. Josefsson, M. Castedal et al., “Hepatic encephalopathy is related to anemia and fat-free mass depletion in liver transplant candidates with cirrhosis,” Scandinavian Journal of Gastroenterology, vol. 48, no. 5, pp. 577–584, 2013. View at Publisher · View at Google Scholar · View at Scopus
  80. K. Kolanjiappan, S. Manoharan, and M. Kayalvizhi, “Measurement of erythrocyte lipids, lipid peroxidation, antioxidants and osmotic fragility in cervical cancer patients,” Clinica Chimica Acta, vol. 326, no. 1-2, pp. 143–149, 2002. View at Publisher · View at Google Scholar · View at Scopus
  81. S. H. Caldwell, M. Hoffman, T. Lisman et al., “Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management,” Hepatology, vol. 44, no. 4, pp. 1039–1046, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. D. E. Choi, K. W. Lee, Y. T. Shin, and K. R. Na, “Hyperammonemia in a patient with late-onset ornithine carbamoyltransferase deficiency,” Journal of Korean Medical Science, vol. 27, no. 5, pp. 556–559, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. J. Albrecht and M. Dolinska, “Glutamine as a pathogenic factor in hepatic encephalopathy,” Journal of Neuroscience Research, vol. 65, no. 1, pp. 1–5, 2001. View at Publisher · View at Google Scholar · View at Scopus
  84. C. H. Dejong, N. E. Deutz, and P. B. Soeters, “Ammonia and glutamine metabolism during liver insufficiency: the role of kidney and brain in interorgan nitrogen exchange,” Scandinavian Journal of Gastroenterology. Supplement, vol. 218, pp. 61–77, 1996. View at Google Scholar
  85. J. Vaquero and R. F. Butterworth, “Mechanisms of brain edema in acute liver failure and impact of novel therapeutic interventions,” Neurological Research, vol. 29, no. 7, pp. 683–690, 2007. View at Google Scholar
  86. E. Kosenko, Y. Kaminsky, E. Grau et al., “Brain ATP depletion induced by acute ammonia intoxication in rats is mediated by activation of the NMDA receptor and Na+,K+-ATPase,” Journal of Neurochemistry, vol. 63, no. 6, pp. 2172–2178, 1994. View at Publisher · View at Google Scholar · View at Scopus
  87. B. Sadasivudu, T. I. Rao, and C. R. Murthy, “Acute metabolic effects of ammonia in mouse brain,” Neurochemical Research, vol. 2, no. 6, pp. 639–655, 1977. View at Publisher · View at Google Scholar · View at Scopus