Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2013 (2013), Article ID 258209, 11 pages
http://dx.doi.org/10.1155/2013/258209
Review Article

Current Perspectives in NSAID-Induced Gastropathy

Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India

Received 30 December 2012; Accepted 14 February 2013

Academic Editor: Eduardo Arranz

Copyright © 2013 Mau Sinha 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. J. R. Vane, “The mode of action of aspirin and similar compounds,” Journal of Allergy and Clinical Immunology, vol. 58, no. 6, pp. 691–712, 1976. View at Google Scholar · View at Scopus
  2. J. R. Vane, “The fight against rheumatism: from willow bark to COX-1 sparing drugs,” Journal of Physiology and Pharmacology, vol. 51, no. 4, pp. 573–586, 2000. View at Google Scholar · View at Scopus
  3. G. Nuki, “Pain control and the use of non-steroidal analgesic anti-inflammatory drugs,” British Medical Bulletin, vol. 46, no. 1, pp. 262–278, 1990. View at Google Scholar · View at Scopus
  4. W. E. Smalley, W. A. Ray, J. R. Daugherty, and M. R. Griffin, “Nonsteroidal anti-inflammatory drugs and the incidence of hospitalizations for peptic ulcer disease in elderly persons,” American Journal of Epidemiology, vol. 141, no. 6, pp. 539–545, 1995. View at Google Scholar · View at Scopus
  5. J. DeRuiter, “Non-steroidal antiinflammatory drugs (NSAIDS),” Principles of Drug Action, vol. 2, pp. 1–25, 2002. View at Google Scholar
  6. W. E. Smalley and R. N. DuBois, “Colorectal cancer and nonsteroidal anti-inflammatory drugs,” Advances in Pharmacology, vol. 39, pp. 1–20, 1997. View at Publisher · View at Google Scholar · View at Scopus
  7. R. N. DuBois and W. E. Smalley, “Cyclooxygenase, NSAIDs, and colorectal cancer,” Journal of Gastroenterology, vol. 31, no. 6, pp. 898–906, 1996. View at Publisher · View at Google Scholar · View at Scopus
  8. J. R. Vane, “Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs,” Nature New Biology, vol. 43, pp. 232–235, 1971. View at Google Scholar
  9. S. H. Saverymuttu, A. Thomas, A. Grundy, and J. D. Maxwell, “Ileal stricturing after long-term indomethacin treatment,” Postgraduate Medical Journal, vol. 62, no. 732, pp. 967–968, 1986. View at Google Scholar · View at Scopus
  10. I. Bjarnason, J. Hayllar, A. J. MacPherson, and A. S. Russell, “Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans,” Gastroenterology, vol. 104, no. 6, pp. 1832–1847, 1993. View at Google Scholar · View at Scopus
  11. C. J. Hawkey, “Nonsteroidal anti-inflammatory drug gastropathy,” Gastroenterology, vol. 119, no. 2, pp. 521–535, 2000. View at Google Scholar · View at Scopus
  12. M. Koch, “Non-steroidal anti-inflammatory drug gastropathy: clinical results with misoprostol,” Italian Journal of Gastroenterology and Hepatology, vol. 31, no. 1, pp. S54–S62, 1999. View at Google Scholar · View at Scopus
  13. C. Scarpignato and I. Pelosini, “Prevention and treatment of non-steroidal anti-inflammatory drug-induced gastro-duodenal damage: rationale for the use of antisecretory compounds,” Italian Journal of Gastroenterology and Hepatology, vol. 31, no. 1, pp. S63–S72, 1999. View at Google Scholar · View at Scopus
  14. L. Laine, “The role of proton pump inhibitors in NSAID—associated gastropathy and upper gastrointestinal symptoms,” Reviews in Gastroenterological Disorders, vol. 3, no. 4, pp. S30–S39, 2003. View at Google Scholar · View at Scopus
  15. R. Micklewright, S. Lane, W. Linley, C. McQuade, F. Thompson, and N. Maskrey, “Review article: NSAIDs, gastroprotection and cyclo-oxygenase-II-selective inhibitors,” Alimentary Pharmacology and Therapeutics, vol. 17, no. 3, pp. 321–332, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. P. Patrignani, S. Tacconelli, and M. L. Capone, “Risk management profile of etoricoxib: an example of personalized medicine,” Therapeutics and Clinical Risk Management, vol. 4, no. 5, pp. 983–997, 2008. View at Google Scholar · View at Scopus
  17. C. Mattia and F. Coluzzi, “Oxycodone. Pharmacological profile and clinical data in chronic pain management,” Minerva Anestesiologica, vol. 71, no. 7-8, pp. 461–470, 2005. View at Google Scholar
  18. J. A. Baron, R. S. Sandler, R. S. Bresalier et al., “Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial,” The Lancet, vol. 372, no. 9651, pp. 1756–1764, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. L. A. García Rodríguez, S. Tacconelli, and P. Patrignani, “Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population,” Journal of the American College of Cardiology, vol. 52, no. 20, pp. 1628–1636, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. F. L. Lanza, F. K. Chan, and E. M. Quigley;, “Practice Parameters Committee of the American College of Gastroenterology, Guidelines for prevention of NSAID-related ulcer complications,” American Journal of Gastroenterology, vol. 104, no. 3, pp. 728–738, 2009. View at Google Scholar
  21. N. G. Vallurupalli and S. Z. Goldhaber, “Gastrointestinal complications of dual antiplatelet therapy,” Circulation, vol. 113, no. 12, pp. e655–e658, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. D. L. Bhatt, J. Scheiman, N. S. Abraham et al., “ACCF/ACG/AHA, 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use,” American Journal of Gastroenterology, vol. 103, no. 11, pp. 2890–2907, 2008. View at Google Scholar
  23. M. Gilard, B. Arnaud, G. Le Gal, J. F. Abgrall, and J. Boschat, “Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin,” Journal of Thrombosis and Haemostasis, vol. 4, no. 11, pp. 2508–2509, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. D. N. Juurlink, T. Gomes, D. T. Ko et al., “A population-based study of the drug interaction between proton pump inhibitors and clopidogrel,” Canadian Medical Association Journal, vol. 180, no. 7, pp. 713–718, 2009. View at Google Scholar
  25. N. S. Abraham, M. A. Hlatky, E. M. Antman et al., “ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use,” American Journal of Gastroenterology, vol. 105, no. 12, pp. 2533–2549, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. N. Muller, E. Payan, F. Lapicque, B. Bannwarth, and P. Netter, “Pharmacological aspects of chiral nonsteroidal anti-inflammatory drugs,” Fundamental and Clinical Pharmacology, vol. 4, no. 6, pp. 617–634, 1990. View at Google Scholar · View at Scopus
  27. R. F. Grace, Y. Lin, S. R. Edwards, I. Power, and L. E. Mather, “Effects of diclofenac in the rat tail ischaemia-reperfusion injury model of acute hyperalgesia,” Pain, vol. 89, no. 2-3, pp. 117–125, 2001. View at Publisher · View at Google Scholar · View at Scopus
  28. D. W. Hahn, R. Carraher, and J. L. McGuire, “Effects of suprofen and other prostaglandin synthetase inhibitors in a new animal model for myometrial hyperactivity,” Prostaglandins, vol. 23, no. 1, pp. 1–16, 1982. View at Publisher · View at Google Scholar · View at Scopus
  29. C. E. Chapleau, R. P. White, and J. T. Robertson, “Cerebral vasodilation and prostacyclin. The effects of aspirin and meclofenamate in vitro,” Journal of Neurosurgery, vol. 53, no. 2, pp. 188–192, 1980. View at Google Scholar · View at Scopus
  30. A. J. Lonigro, M. H. Hagemann, A. H. Stephenson, and C. L. Fry, “Inhibition of prostaglandin synthesis by indomethacin augments the renal vasodilator response to bradykinin in the anesthetized dog,” Circulation Research, vol. 43, no. 3, pp. 447–455, 1978. View at Google Scholar · View at Scopus
  31. A. Morimoto, N. Murakami, and T. Watanabe, “Effect of prostaglandin E2 on thermoresponsive neurones in the preoptic and ventromedial hypothalamic regions of rats,” Journal of Physiology, vol. 405, pp. 713–725, 1988. View at Google Scholar · View at Scopus
  32. A. Wit and S. C. Wang, “Temperature-sensitive neurons in preoptic-anterior hypothalamic region: actions of pyrogen and acetylsalicylate,” The American Journal of Physiology, vol. 215, no. 5, pp. 1160–1169, 1968. View at Google Scholar · View at Scopus
  33. F. H. Lovejoy Jr., “Aspirin and acetaminophen: a comparative view of their antipyretic and analgesic activity,” Pediatrics, vol. 62, no. 5, part 2, pp. 904–909, 1978. View at Google Scholar · View at Scopus
  34. N. Zidar, K. Odar, D. Glavac, M. Jerse, T. Zupanc, and D. Stajer, “Cyclooxygenase in normal human tissues—is COX-1 really a constitutive isoform, and COX-2 an inducible isoform?” Cellular and Molecular Medicine B, vol. 13, no. 9, pp. 3753–3763, 2009. View at Google Scholar
  35. K. Gudis and C. Sakamoto, “The role of cyclooxygenase in gastric mucosal protection,” Digestive Diseases and Sciences, vol. 50, no. 1, pp. S16–S23, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. S. J. Konturek, P. C. Konturek, T. Pawlik, Z. Sliwowski, W. Ochmański, and E. G. Hahn, “Duodenal mucosal protection by bicarbonate secretion and its mechanisms,” Journal of Physiology and Pharmacology, vol. 55, pp. 5–17, 2004. View at Google Scholar · View at Scopus
  37. K. Seibert, Y. Zhang, K. Leahy et al., “Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain,” Proceedings of National Academy of Sciences, vol. 91, no. 25, pp. 12013–12017, 1994. View at Google Scholar
  38. K. Seibert and J. L. Masferrer, “Role of inducible cyclooxygenase (COX-2) in inflammation,” Receptor, vol. 4, no. 1, pp. 17–23, 1994. View at Google Scholar · View at Scopus
  39. J. A. Mitchell, P. Akarasereenont, C. Thiemermann, R. J. Flower, and J. R. Vane, “Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 24, pp. 11693–11697, 1993. View at Publisher · View at Google Scholar · View at Scopus
  40. L. Laine, “Nonsteroidal anti-inflammatory drug gastropathy,” Gastrointestinal Endoscopy Clinics of North America, vol. 6, no. 3, pp. 489–504, 1996. View at Google Scholar · View at Scopus
  41. T. A. Miller, “Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms,” The American Journal of Physiology, vol. 245, no. 5, part 1, pp. G601–G623, 1983. View at Google Scholar · View at Scopus
  42. S. Somasundaram, S. Rafi, J. Hayllar et al., “Mitochondrial damage: a possible mechanism of the 'topical' phase of NSAID induced injury to the rat intestine,” Gut, vol. 41, no. 3, pp. 344–353, 1997. View at Google Scholar · View at Scopus
  43. W. Tomisato, C. K. Tanaka, T. Katsu et al., “Membrane permeabilization by non-steroidal anti-inflammatory drugs,” Biochemical and Biophysical Research Communications, vol. 323, no. 2, pp. 1032–1039, 2004. View at Publisher · View at Google Scholar
  44. L. M. Lichtenberger, “Where is the evidence that cyclooxygenase inhibition is the primary cause of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal injury? Topical injury revisited,” Biochemical Pharmacology, vol. 61, no. 6, pp. 631–637, 2001. View at Publisher · View at Google Scholar · View at Scopus
  45. H. W. Davenport, “Salicylate damage to the gastric mucosal barrier,” The New England Journal of Medicine, vol. 276, no. 23, pp. 1307–1312, 1967. View at Google Scholar
  46. L. M. Lichtenberger, “The hydrophobic barrier properties of gastrointestinal mucus,” Annual Review of Physiology, vol. 57, pp. 565–583, 1995. View at Google Scholar · View at Scopus
  47. W. Tomisato, S. Tsutsumi, K. Rokutan, T. Tsuchiya, and T. Mizushima, “NSAIDs induce both necrosis and apoptosis in guinea pig gastric mucosal cells in primary culture,” American Journal of Physiology, vol. 281, no. 4, pp. G1092–G1100, 2001. View at Google Scholar · View at Scopus
  48. P. M. Vaananen, C. M. Keenan, M. B. Grisham, and J. L. Wallace, “Pharmacological investigation of the role of leukotrienes in the pathogenesis of experimental NSAID gastropathy,” Inflammation, vol. 16, no. 3, pp. 227–240, 1992. View at Google Scholar · View at Scopus
  49. N. Hudson, M. Balsitis, S. Everitt, and C. J. Hawkey, “Enhanced gastric mucosal leukotriene B4 synthesis in patients taking non-steroidal anti-inflammatory drugs,” Gut, vol. 34, no. 6, pp. 742–747, 1993. View at Google Scholar · View at Scopus
  50. B. M. Peskar, “Role of leukotriene C4 in mucosal damage caused by necrotizing agents and indomethacin in the rat stomach,” Gastroenterology, vol. 100, no. 3, pp. 619–626, 1991. View at Google Scholar · View at Scopus
  51. D. M. McCafferty, D. N. Granger, and J. L. Wallace, “Indomethacin-induced gastric injury and leukocyte adherence in arthritic versus healthy rats,” Gastroenterology, vol. 109, no. 4, pp. 1173–1180, 1995. View at Publisher · View at Google Scholar · View at Scopus
  52. F. J. Andrews, C. Malcontenti-Wilson, and P. E. O'Brien, “Effect of nonsteroidal anti-inflammatory drugs on LFA-1 and ICAM-1 expression in gastric mucosa,” American Journal of Physiology, vol. 266, no. 4, part 1, pp. G657–G664, 1994. View at Google Scholar · View at Scopus
  53. L. Santucci, S. Fiorucci, M. Giansanti, P. M. Brunori, F. M. Di Matteo, and A. Morelli, “Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: role of tumour necrosis factor alpha,” Gut, vol. 35, no. 7, pp. 909–915, 1994. View at Google Scholar · View at Scopus
  54. J. L. Wallace, “Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years,” Gastroenterology, vol. 112, no. 3, pp. 1000–1016, 1997. View at Publisher · View at Google Scholar · View at Scopus
  55. F. E. Silverstein, D. Y. Graham, J. R. Senior et al., “Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial,” Annals of Internal Medicine, vol. 123, no. 4, pp. 241–249, 1995. View at Google Scholar · View at Scopus
  56. Y. Graham, R. H. White, L. W. Moreland et al., “Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group,” Annals of Internal Medicine, vol. 119, no. 4, pp. 257–262, 1993. View at Google Scholar
  57. J. L. Goldstein, L. R. Larson, and B. D. Yamashita, “Prevention of nonsteroidal anti-inflammatory drug-induced gastropathy: clinical and economic implications of a single-tablet formulation of diclofenac/misoprostol,” American Journal of Managed Care, vol. 4, no. 5, pp. 687–697, 1998. View at Google Scholar · View at Scopus
  58. D. Lapenna, S. De Gioia, A. Mezzetti et al., “H2-receptor antagonists are scavengers of oxygen radicals,” European Journal of Clinical Investigation, vol. 24, no. 7, pp. 476–481, 1994. View at Google Scholar · View at Scopus
  59. 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,” Journal of Biological Chemistry, vol. 278, no. 13, pp. 10993–11001, 2003. View at Publisher · View at Google Scholar · View at Scopus
  60. M. G. Robinson, J. W. Griffin, J. Bowers et al., “Effect of ranitidine gastroduodenal mucosal damage induced by nonsteroidal antiinfalmmatory drugs,” Digestive Diseases and Sciences, vol. 34, no. 3, pp. 424–428, 1989. View at Google Scholar · View at Scopus
  61. R. S. B. Ehsanullah, M. C. Page, G. Tildesley, and J. R. Wood, “Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine,” British Medical Journal, vol. 297, no. 6655, pp. 1017–1021, 1988. View at Google Scholar · View at Scopus
  62. M. M. Wolfe, D. R. Lichtenstein, and G. Singh, “Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs,” The New England Journal of Medicine, vol. 341, no. 7, pp. 1888–1899, 1999. View at Google Scholar
  63. N. J. Bell and R. H. Hunt, “Progress with proton pump inhibition,” Yale Journal of Biology and Medicine, vol. 65, no. 6, pp. 649–657, 1992. View at Google Scholar
  64. L. Laine, “Proton pump inhibitor co-therapy with nonsteroidal anti-inflammatory drugs—nice or necessary?” Reviews in Gastroenterological Disorders, vol. 4, supplement 4, pp. S33–S41, 2004. View at Google Scholar · View at Scopus
  65. J. Hawkey, J. A. Karrasch, L. Szczepanski et al., “Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprozole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group,” The New England Journal of Medicine, vol. 338, no. 11, pp. 727–734, 1998. View at Google Scholar
  66. L. S. Welage and R. R. Berardi, “Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases,” Journal of the American Pharmaceutical Association, vol. 40, no. 1, pp. 52–62, 2000. View at Google Scholar · View at Scopus
  67. F. Baldi and P. Malfertheiner, “Lansoprazole fast disintegrating tablet: a new formulation for an established proton pump inhibitor,” Digestion, vol. 67, no. 1-2, pp. 1–5, 2003. View at Publisher · View at Google Scholar · View at Scopus
  68. N. D. Yeomans, C. J. Hawkey, R. Jones et al., “Esomeprazole provides effective control of NSAID-associated upper GI symptoms in patients continuing to take NSAIDs,” Gastroenterology, vol. 124, supplement 1, no. 4, p. A107, 2003. View at Google Scholar
  69. C. H. Wilder-Smith, K. Röhss, C. Nilsson-Pieschl, O. Junghard, and L. Nyman, “Esomeprazole 40 mg provides improved intragastric acid control as compared with lansoprazole 30 mg and rabeprazole 20 mg in healthy volunteers,” Digestion, vol. 68, no. 4, pp. 184–188, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. P. J. Kahrilas, G. W. Falk, D. A. Johnson et al., “Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial,” Alimentary Pharmacology and Therapeutics, vol. 14, no. 10, pp. 1249–1258, 2000. View at Publisher · View at Google Scholar · View at Scopus
  71. A. ] Gigante and I. Tagarro, “Non-steroidal anti-inflammatory drugs and gastroprotection with proton pump inhibitors: a focus on ketoprofen/omeprazole,” Clinical Drug Investigation, vol. 32, no. 4, pp. 221–231, 2012. View at Google Scholar
  72. D. L. Bhatt and E. J. Topol, “Clopidogrel added to aspirin versus aspirin alone in secondary prevention and high-risk primary prevention: rationale and design of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial,” American Heart Journal, vol. 148, no. 2, pp. 263–268, 2004. View at Publisher · View at Google Scholar · View at Scopus
  73. D. L. Bhatt, K. A. Fox, W. Hacke et al., “Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events,” The New England Journal of Medicine, vol. 354, no. 16, pp. 1706–1717, 2006. View at Publisher · View at Google Scholar
  74. J. M. Pereillo, M. Maftouh, A. Andrieu et al., “Structure and stereochemistry of the active metabolite of clopidogrel,” Drug Metabolism and Disposition, vol. 30, no. 11, pp. 1288–1295, 2002. View at Publisher · View at Google Scholar · View at Scopus
  75. S. M. Bhurke, B. C. Martin, C. Li, A. M. Franks, Z. Bursac, and Q. Said, “Effect of the clopidogrel-proton pump inhibitor drug interaction on adverse cardiovascular events in patients with acute coronary syndrome,” Pharmacotherapy, vol. 32, no. 9, pp. 809–818, 2012. View at Google Scholar
  76. M. Gilard, B. Arnaud, J. C. Cornily et al., “Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin. The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study,” Journal of the American College of Cardiology, vol. 51, no. 3, pp. 256–260, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. P. M. Ho, T. M. Maddox, L. Wang et al., “Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome,” The Journal of the American Medical Association, vol. 301, no. 9, pp. 937–944, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. D. L. Bhatt, B. L. Cryer, C. F. Contant et al., “Clopidogrel with or without omeprazole in coronary artery disease,” The New England Journal of Medicine, vol. 363, no. 20, pp. 1909–1917, 2010. View at Google Scholar
  79. M. L. O'Donoghue, E. Braunwald, E. M. Antman et al., “Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials,” The Lancet, vol. 374, no. 9694, pp. 989–997, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. J. P. Depta and D. L. Bhatt, “Omeprazole and clopidogrel: should clinicians be worried?” Cleveland Clinic Journal of Medicine, vol. 77, no. 2, pp. 113–116, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. E. C. Klinkenberg-Knol, F. Nelis, J. Dent et al., “Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa,” Gastroenterology, vol. 118, no. 4, pp. 661–669, 2000. View at Google Scholar · View at Scopus
  82. A. Meining, G. Kiel, and M. Stolte, “Changes in Helicobacter pylori-induced gastritis in the antrum and corpus during and after 12 months of treatment with ranitidine and lansoprazole in patients with duodenal ulcer disease,” Alimentary Pharmacology and Therapeutics, vol. 12, no. 8, pp. 735–740, 1998. View at Publisher · View at Google Scholar · View at Scopus
  83. K. K. Wu, “Cyclooxygenase 2 induction: molecular mechanism and pathophysiologic roles,” Journal of Laboratory and Clinical Medicine, vol. 128, no. 3, pp. 242–245, 1996. View at Google Scholar
  84. J. L. Masferrer, P. C. Isakson, and K. Seibert, “Cyclooxygenase-2 inhibitors: a new class of anti-inflammatory agents that spare the gastrointestinal tract,” Gastroenterology Clinics of North America, vol. 25, no. 2, pp. 363–372, 1996. View at Publisher · View at Google Scholar · View at Scopus
  85. C. C. Chan and I. W. Rodger, “Selective cyclooxygenase-2 inhibitors as potential therapeutic agents for inflammatory diseases,” Advances in Experimental Medicine and Biology, vol. 407, pp. 157–161, 1997. View at Google Scholar · View at Scopus
  86. C. Bombardier, L. Laine, A. Reicin et al., “Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis,” The New England Journal of Medicine, vol. 343, no. 21, pp. 1520–1528, 2000. View at Publisher · View at Google Scholar · View at Scopus
  87. F. E. Silverstein, G. Faich, J. L. Goldstein et al., “Gastrointestinal toxicity with Celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and reumatoid arthritis: the CLASS study: a randomized controlled trial,” The Journal of the American Medical Association, vol. 284, no. 10, pp. 1247–1255, 2000. View at Google Scholar · View at Scopus
  88. C. K. Lau, W. C. Black, M. Belley et al., “From indomethacin to a selective COX-2 inhibitor: development of indolalkanoic acids as potent and selective cyclooxygenase-2 inhibitors,” Advances in Experimental Medicine and Biology, vol. 407, pp. 73–78, 1996. View at Google Scholar · View at Scopus
  89. D. Riendeau, M. D. Percival, S. Boyce et al., “Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor,” British Journal of Pharmacology, vol. 121, no. 1, pp. 105–117, 1997. View at Google Scholar
  90. L. J. Marnett and A. S. Kalgutkar, “Design of selective inhibitors of cyclooxygenase-2 as nonulcerogenic anti-inflammatory agents,” Current Opinion in Chemical Biology, vol. 2, no. 4, pp. 482–490, 1998. View at Google Scholar · View at Scopus
  91. T. D. Penning, J. J. Talley, S. R. Bertenshaw et al., “Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)- 3(trifluoromethyl)-1h-pyrazol-1-yl]benzenesulfonamide (sc-58635, celecoxib),” Journal of Medicinal Chemistry, vol. 40, no. 9, pp. 1347–1365, 1997. View at Publisher · View at Google Scholar · View at Scopus
  92. L. S. Simon, F. L. Lanza, P. E. Lipsky et al., “Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects,” Arthritis Rheumatism, vol. 41, no. 9, pp. 1591–1602, 1998. View at Google Scholar
  93. L. S. Simon, A. L. Weaver, D. Y. Graham et al., “Anti-inflammatory andupper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial,” The Journal of American Medical Association, vol. 282, no. 20, pp. 1921–1928, 1999. View at Google Scholar
  94. F. K. Chan, L. C. Hung, B. Y. Suen et al., “Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis,” The New England Journal of Medicine, vol. 347, pp. 2104–2110, 2002. View at Publisher · View at Google Scholar
  95. L. Laine, S. Harper, T. Simon et al., “A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis,” Gastroenterology, vol. 117, no. 4, pp. 776–783, 1999. View at Publisher · View at Google Scholar · View at Scopus
  96. E. Woolf, I. Fu, and B. Matuszewski, “Determination of rofecoxib, a cyclooxygenase-2 specific inhibitor, in human plasma using high-performance liquid chromatography with post-column photochemical derivatization and fluorescence detection,” Journal of Chromatography B, vol. 730, no. 2, pp. 221–227, 1999. View at Publisher · View at Google Scholar · View at Scopus
  97. T. J. Schnitzer, K. Truitt, R. Fleischmann et al., “The safety profile, tolerability, and effective dose range of rofecoxib in the treatment of rheumatoid arthritis,” Clinical Therapeutics, vol. 21, no. 10, pp. 1688–1702, 1999. View at Publisher · View at Google Scholar · View at Scopus
  98. L. Cullen, L. Kelly, S. O. Connor, and D. J. Fitzgerald, “Selective cyclooxygenase-2 inhibition by nimesulide in man,” Journal of Pharmacology and Experimental Therapeutics, vol. 287, no. 2, pp. 578–582, 1998. View at Google Scholar · View at Scopus
  99. P. Patrignani, S. Tacconelli, and M. L. Capone, “Risk management profile of etoricoxib: an example of personalized medicine,” Therapeutics and Clinical Risk Management, vol. 4, no. 5, pp. 983–997, 2008. View at Google Scholar · View at Scopus
  100. C. Mattia and F. Coluzzi, “COX-2 inhibitors: pharmacological data and adverse effects,” Minerva Anesthesiology, vol. 71, no. 7-8, pp. 461–470, 2005. View at Google Scholar
  101. L. A. G. Rodríguez, S. Tacconelli, and P. Patrignani, “Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population,” Journal of the American College of Cardiology, vol. 52, no. 20, pp. 1628–1636, 2008. View at Google Scholar
  102. P. L. McGeer, E. G. McGeer, and K. Yasojima, “Cardiovascular events and COX-2 inhibitors,” The Journal of American Medical Association, vol. 286, no. 22, p. 2810, 2001. View at Google Scholar
  103. J. K. Hennan, J. Huang, T. D. Barrett et al., “Effects of selective cyclooxygenase-2 inhibition on vascular responses and thrombosis in canine coronary arteries,” Circulation, vol. 104, no. 7, pp. 820–825, 2001. View at Google Scholar · View at Scopus
  104. D. Mukherjee, S. E. Nissen, and E. J. Topol, “Risk of cardiovascular events associated with selective COX-2 inhibitors,” The Journal of the American Medical Association, vol. 286, no. 8, pp. 954–959, 2001. View at Google Scholar · View at Scopus
  105. J. Y. Jeremy, D. P. Mikhailidis, M. A. Barradas, R. M. Kirk, and P. Dandona, “The effect of nabumetone and its principal active metabolite on in vitro human gastric mucosal prostanoid synthesis and platelet function,” British Journal of Rheumatology, vol. 29, no. 2, pp. 116–119, 1990. View at Google Scholar · View at Scopus
  106. M. A. Konstam and M. R. Weir, “Current perspective on the cardiovascular effects of coxibs,” Cleveland Clinic Journal of Medicine, vol. 69, supplement 1, pp. SI47–SI52, 2002. View at Google Scholar · View at Scopus
  107. A. Nguyen and A. Chaiton, “Cyclooxygenase (COX-2) selective inhibitors: any better than NSAIDs?” Canadian Family Physician, vol. 47, pp. 1398–1400, 2001. View at Google Scholar · View at Scopus
  108. B. Sibbald, “Rofecoxib (Vioxx) voluntarily withdrawn from market,” Canadian Medical Association Journal, vol. 171, no. 9, pp. 1027–1028, 2004. View at Google Scholar · View at Scopus
  109. J. E. Saavedra, T. R. Billiar, D. L. Williams, Y. M. Kim, S. C. Watkins, and L. K. Keefer, “Targeting nitric oxide (NO) delivery in vivo. Design of a liver- selective NO donor prodrug that blocks tumor necrosis factor-α-induced apoptosis and toxicity in the liver,” Journal of Medicinal Chemistry, vol. 40, no. 13, pp. 1947–1954, 1997. View at Publisher · View at Google Scholar · View at Scopus
  110. K. R. A. Abdellatif, M. A. Chowdhury, Y. Dong et al., “Dinitroglyceryl and diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of aspirin, indomethacin and ibuprofen: synthesis, biological evaluation and nitric oxide release studies,” Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 11, pp. 3014–3018, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. W. Fan, Y. Wu, X. K. Li et al., “Design, synthesis and biological evaluation of brain-specific glucosyl thiamine disulfide prodrugs of naproxen,” European Journal of Medicinal Chemistry, vol. 46, no. 9, pp. 3651–3661, 2011. View at Publisher · View at Google Scholar
  112. S. C. Young, K. M. Fabio, M. T. Huang et al., “Investigation of anticholinergic and non-steroidal anti-inflammatory prodrugs which reduce chemically induced skin inflammation,” Journal of Applied Toxicology, vol. 32, no. 2, pp. 135–141, 2012. View at Publisher · View at Google Scholar
  113. A. M. Qandil, “Prodrugs of nonsteroidal anti-inflammatory drugs (NSAIDs), more than meets the eye: a critical review,” International Journal of Molecular Sciences, vol. 13, no. 12, pp. 17244–17274, 2012. View at Publisher · View at Google Scholar
  114. S. J. Konturek, T. Brzozowski, J. Majka, A. Szlachcic, and J. Pytko-Polonczyk, “Implications of nitric oxide in the action of cytoprotective drugs on gastric mucosa,” Journal of Clinical Gastroenterology, vol. 17, supplement 1, pp. S140–S145, 1993. View at Google Scholar · View at Scopus
  115. S. J. Konturek, T. Brzozowski, J. Majka, A. Szlachcic, and K. Czarnobilski, “Nitric oxide in gastroprotection by sucralfate, mild irritant, and nocloprost: role of mucosal blood flow,” Digestive Diseases and Sciences, vol. 39, no. 3, pp. 593–600, 1994. View at Google Scholar · View at Scopus
  116. A. Szlachcic, G. Krzysiek-Maczka, R. Pajdo et al., “The impact of asymmetric dimethylarginine (ADAMA), the endogenous nitric oxide (NO) synthase inhibitor, to the pathogenesis of gastric mucosal damage,” Current Pharmaceutical Design, vol. 19, no. 1, pp. 90–97, 2013. View at Google Scholar
  117. J. L. Wallace and M. J. S. Miller, “Nitric oxide in mucosal defense: a little goes a long way,” Gastroenterology, vol. 119, no. 2, pp. 512–520, 2000. View at Google Scholar · View at Scopus
  118. E. Koç and S. G. Küçükgüzel, “Medicinal chemistry and anti-inflammatory activity of nitric oxide-releasing NSAI drugs,” Mini-Reviews in Medicinal Chemistry, vol. 9, no. 5, pp. 611–619, 2009. View at Google Scholar
  119. S. Fiorucci, E. Antonelli, L. Santucci et al., “Gastrointestinal safety of nitric oxide-derived aspirin is related to inhibition of ICE-like cysteine proteases in rats,” Gastroenterology, vol. 116, no. 5, pp. 1089–1106, 1999. View at Publisher · View at Google Scholar · View at Scopus
  120. N. M. Davies, A. G. Roøseth, C. B. Appleyard et al., “NO-naproxen vs. naproxen: ulcerogenic, analgesic and anti-inflammatory effects,” Alimentary Pharmacology and Therapeutics, vol. 11, no. 1, pp. 69–79, 1997. View at Google Scholar · View at Scopus
  121. K. Takeuchi, H. Mizoguchi, H. Araki, Y. Komoike, and K. Suzuki, “Lack of gastric toxicity of nitric oxide-releasing indomethacin, NCX-530, in experimental animals,” Digestive Diseases and Sciences, vol. 46, no. 8, pp. 1805–1818, 2001. View at Publisher · View at Google Scholar · View at Scopus
  122. C. Cicala, A. Ianaro, S. Fiorucci et al., “NO-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freund's adjuvant arthritis,” British Journal of Pharmacology, vol. 130, no. 6, pp. 1399–1405, 2000. View at Google Scholar · View at Scopus
  123. J. E. Keeble and P. K. Moore, “Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs,” British Journal of Pharmacology, vol. 137, no. 3, pp. 295–310, 2002. View at Publisher · View at Google Scholar · View at Scopus
  124. J. L. Wallace, W. McKnight, P. Del Soldato, A. R. Baydoun, and G. Cirino, “Anti-thrombotic effects of a nitric oxide-releasing, gastric-sparing aspirin derivative,” Journal of Clinical Investigation, vol. 96, no. 6, pp. 2711–2718, 1995. View at Google Scholar · View at Scopus
  125. S. Fiorucci, E. Antonelli, A. Mencarelli et al., “The third gas: H2S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis,” Hepatology, vol. 42, no. 3, pp. 539–548, 2005. View at Publisher · View at Google Scholar · View at Scopus
  126. J. L. Wallace, “Hydrogen sulfide-releasing anti-inflammatory drugs,” Trends in Pharmacological Sciences, vol. 28, no. 10, pp. 501–505, 2007. View at Google Scholar
  127. Y. J. Lim, J. S. Lee, Y. S. Ku, and K. B. Hahm, “Rescue strategies against non-steroidal anti-inflammatory drug-induced gastroduodenal damage,” Journal of Gastroenterology and Hepatology, vol. 24, no. 7, pp. 1169–1178, 2009. View at Publisher · View at Google Scholar · View at Scopus
  128. L. Liu, J. Cui, C. J. Song et al., “H(2)S-releasing aspirin protects against aspirin-induced gastric injury via reducing oxidative stress,” PLoS One, vol. 7, no. 9, Article ID e46301, 2012. View at Google Scholar
  129. L. M. Lichtenberger, M. Barron, and U. Marathi, “Association of phosphatidylcholine and nsaids as a novel strategy to reduce gastrointestinal toxicity,” Drugs of Today, vol. 45, no. 12, pp. 877–890, 2009. View at Publisher · View at Google Scholar · View at Scopus
  130. L. M. Lichtenberger, Y. Zhou, V. Jayaraman et al., “Insight into NSAID-induced membrane alterations, pathogenesis and therapeutics: characterization of interaction of NSAIDs with phosphatidylcholine,” Biochimica et Biophysica Acta, vol. 1821, no. 7, pp. 994–1002, 2012. View at Google Scholar
  131. J. L. Santos, V. Moreira, M. L. Campos et al., “Pharmacological evaluation and preliminary pharmacokinetics studies of a new diclofenac prodrug without gastric ulceration effect,” International Journal of Molecular Sciences, vol. 13, no. 11, pp. 15305–15320, 2012. View at Publisher · View at Google Scholar
  132. K. D. Rainsford, “Ibuprofen: from invention to an OTC therapeutic mainstay,” International Journal of Clinical Practice, vol. 178, pp. 9–20, 2013. View at Google Scholar
  133. J. Martel-Pelletier, D. Lajeunesse, P. Reboul, and J. P. Pelletier, “Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective non-steroidal anti-inflammatory drugs,” Annals of the Rheumatic Diseases, vol. 62, no. 6, pp. 501–509, 2003. View at Publisher · View at Google Scholar · View at Scopus
  134. M. M. Skelly and C. J. Hawkey, “Dual COX inhibition and upper gastrointestinal damage,” Current Pharmaceutical Design, vol. 9, no. 27, pp. 2191–2195, 2003. View at Publisher · View at Google Scholar · View at Scopus
  135. J. L. Wallace, L. Carter, W. McKnight, S. Tries, and S. Laufer, “ML 3000 reduces gastric prostaglandin synthesis without causing mucosal injury,” European Journal of Pharmacology, vol. 271, no. 2-3, pp. 525–531, 1994. View at Publisher · View at Google Scholar · View at Scopus
  136. S. K. Kulkarni and V. P. Singh, “Licofelone—a novel analgesic and anti-inflammatory agent,” Current Topics in Medicinal Chemistry, vol. 7, no. 3, pp. 251–263, 2007. View at Google Scholar
  137. H. Ulbrich, O. Soehnlein, X. Xie et al., “Licofelone, a novel 5-LOX/COX-inhibitor, attenuates leukocyte rolling and adhesion on endothelium under flow,” Biochemical Pharmacology, vol. 70, no. 1, pp. 30–36, 2005. View at Publisher · View at Google Scholar · View at Scopus
  138. F. Celotti and T. Durand, “The metabolic effects of inhibitors of 5-lipoxygenase and of cyclooxygenase 1 and 2 are an advancement in the efficacy and safety of anti-inflammatory therapy,” Prostaglandins and Other Lipid Mediators, vol. 71, no. 3-4, pp. 147–162, 2003. View at Publisher · View at Google Scholar · View at Scopus
  139. A. F. Cicero and L. Laghi, “Activity and potential role of licofelone in the management of osteoarthritis,” Clinical Interventions in Aging, vol. 2, no. 1, pp. 73–79, 2007. View at Publisher · View at Google Scholar · View at Scopus
  140. S. Tries, W. Neupert, and S. Laufer, “The mechanism of action of the new antiinflammatory compound ML3000: inhibition of 5-LOX and COX-1/2,” Inflammation Research, vol. 51, no. 3, pp. 135–143, 2002. View at Google Scholar · View at Scopus
  141. D. F. V. Lewis, C. Ioannides, and D. V. Parke, “A retrospective study of the molecular toxicology of benoxaprofen,” Toxicology, vol. 65, no. 1-2, pp. 33–47, 1990. View at Publisher · View at Google Scholar · View at Scopus
  142. R. J. Playford, D. N. Floyd, C. E. Macdonald et al., “Bovine colostrum is a health food supplement which prevents NSAID induced gut damage,” Gut, vol. 44, no. 5, pp. 653–658, 1999. View at Google Scholar · View at Scopus
  143. R. J. Playford, C. E. Macdonald, D. P. Calnan et al., “Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability,” Clinical Science, vol. 100, no. 6, pp. 627–633, 2001. View at Publisher · View at Google Scholar · View at Scopus
  144. F. J. Troost, W. H. M. Saris, and R. J. M. Brummer, “Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers,” European Journal of Clinical Nutrition, vol. 57, no. 12, pp. 1579–1585, 2003. View at Publisher · View at Google Scholar · View at Scopus
  145. E. J. Dial, A. J. Dohrman, J. J. Romero, and L. M. Lichtenberger, “Recombinant human lactoferrin prevents NSAID-induced intestinal bleeding in rodents,” Journal of Pharmacy and Pharmacology, vol. 57, no. 1, pp. 93–99, 2005. View at Publisher · View at Google Scholar · View at Scopus
  146. S. Sharma, T. P. Singh, and K. L. Bhatia, “Preparation and characterization of the N and C monoferric lobes of buffalo lactoferrin produced by proteolysis using proteinase K,” Journal of Dairy Research, vol. 66, no. 1, pp. 81–90, 1999. View at Publisher · View at Google Scholar · View at Scopus
  147. R. Mir, N. Singh, G. Vikram et al., “The structural basis for the prevention of nonsteroidal antiinflammatory drug-induced gastrointestinal tract damage by the C-lobe of bovine colostrum lactoferrin,” Biophysical Journal, vol. 97, no. 12, pp. 3178–3186, 2009. View at Publisher · View at Google Scholar · View at Scopus
  148. R. Mir, N. Singh, G. Vikram et al., “Structural and binding studies of C-terminal half (C-lobe) of lactoferrin protein with COX-2-specific non-steroidal anti-inflammatory drugs (NSAIDs),” Archives of Biochemistry and Biophysics, vol. 500, no. 2, pp. 196–202, 2010. View at Publisher · View at Google Scholar · View at Scopus