THE ULCEROGENIC EFFECT OF NON-STEROID ANTI-INFLAMMATORy DRUGS AND HEPATOTOXICITy OF NIMESULIDE IN EXPERIMENT ON RATS

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Abstract

In animal experimental model the ulcerogenic effect of non-selective and selective inhibitors of cyclooxigenase has been estimated. The all tested remedies influenced morphology of liver and mucosa of stomach. Meanwhile the reaction of each animal on non-steroidal anti-inflammatory drugs was individual. It has been elucidated that ketorolac significantly down-regulated prostaglandin E2 production in gut mucosa. Nimesulide (selective non-steroidal anti-inflammatory drug) significantly up-regulated the activity of aspartat-aminotransferase in serum of experimental rats. The mechanism of nimesulide hepatotoxicity is being discussed.

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About the authors

Sergei Nikolayevich Proshin

I. I. Mechnikov North-West State Medical University

Email: psnjsn@rambler.ru
D.Sci. (Pharmacology), Associate Professor (Dozent), Department of Pharmacology

Valerii Gennad’evich Makarov

Joint-stock company “Institute of Pharmacy of St.Petersburg”

D.Sci. (Pharmacology), Direktor-Generale

Marina Nikolaevna Makarova

Joint-stock company “Institute of Pharmacy of St.Petersburg”

D.Sci. (Pharmacology), Deputy of Direktor-Generale

Kirill Leonidovich Kryshen

Joint-stock company “Institute of Pharmacy of St.Petersburg”

Senior researcher (Biochemistry)

Artem Viktorovich Kovshin

I. I. Mechnikov North-West State Medical University, St.Petersburg

assistant, Department of Pharmacology

Igor Alekseevich Samusenko

Joint-stock company “Institute of Pharmacy of St.Petersburg”

Ph.D. (Pathological Anatomy)

References

  1. Хрупкин В. И. Неотложная эндоваскулярная хирургия гастродуоденальных кровотечений / В. И. Хрупкин, М. Д. Ханевич, В. Ф. Зубрицкий, А. Д. Тиканадзе. — М. : Петрозаводск: ИнтелТек, 2002. — 88 с.
  2. Шабанов П. Д., Султанов В. С., Бычков Е. Р., Лебедев А. А., Прошин С. Н. Эффекты полипренольного препарата ропрен при токсическом поражении печени и головного мозга у крыс: изучение функционального состояния печени, поведения и метаболизма моноаминов в мозге // Обзоры по клинической фармакологии и лекарственной терапии. — 2010. — Том. 8. (выпуск 3). С.23–50.
  3. Abdel–Bakky M. S., Hammad M. A., Walkerit L. A., Ashfaqi M. K. Developing and characterizing a mouse model of hepatotoxicity using oral pyrrolizidine alkaloid (monocrotaline) administration, with potentiation of the liver injury by co–administration of LPS // Nat. Prod. Commun. — 2010. — Vol. 5, N. 9. — P. 1457–1462.
  4. Allison M. C., Howatson A. G., Torrance C. J., Lee F. D., Russell R. I. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs // N. Engl. J. Med. — 1992. — Vol. 327, N. 11. — P. 749–754.
  5. Bradford M. M. Rapid and sensitive method for the quantitation of protein utilizing the principle of protein-dye binding // Anal. Biochem. — 1976. — Vol. 72. — P. 248–254.
  6. Browne G. S., Nelson C., Nguven T., Ellis B. A., Day R. O., Williams K. M. Stereoselective and substrate-dependent inhibition of hepatic mitochondria beta-oxidation and oxidative phosphorylation by the non-steroidal anti-inflammatory drugs ibuprofen, flubriprofen, and ketorolac // Biochem. Pharmacol. — 1999. — Vol. 57, N. 7. — P. 837–844.
  7. Buckley M. M., Brogden R. N. Ketorolac. A review of its pfarmacodynamic and pharmacokinetic properties, and therapeutic potential // Drugs. — 1990. — Vol. 39. — P. 86–109.
  8. Chen C. J., Kono H., Golenbock D., Reed G., Akira S., Rock K. L.Identification of a key pathway required for the sterile inflammatory response triggered by dying cells // Nat. Med. — 2007. — Vol. 13. — P. 851–856.
  9. Costantini R., Affaitati G., Fabrizio A., Giamberardino M. A. Controlling pain in the post-operative setting // Int. J. Clin. Pharmacol. Ther. — 2011. — Vol. 49, N. 2. — P. 116–127.
  10. Doñate F., Artiques A., Iriarte A., Martinez-Carrion M. Opposite behavior of two isozymes when refolding in the presence of non-ionic detergents // Protein Sci. — 1998. — Vol. 7, N. 8. — P. 1811–1820.
  11. Dubois R. N., Abramson S. B., Crofford L., Gupta R. A., Simon L. S., Van de Putte L. B., Lipsky P. E. Cyclooxygenase in biology and disease // FASEB J. — 1998. — Vol. 12. — P. 1063–1073.
  12. Fitzgerald G. A., Patrono C. The coxibs, selective inhibitor of cyclooxygenase-2 // N. Engl. J. Med. — 2001. — Vol. 345. — P. 433–442.
  13. Fogel-Petrovic M., Long J. A., Knight D. A., Thompson P. J., Upham J. W. Activated human dendritic cells express inducible cyclooxygenase and synthesize prostaglandin E2 but not prostaglandin D2 // Immunol. Cell Biol. — 2004. — Vol. 82. — P. 47–54.
  14. Giboney P. T. Mildly elevated liver transaminase levels in the asymptomatic patient // Am. Fam. Physician. — 2005. — Vol. 71, N. 6. — P. 1105–1110.
  15. Guo J. S., Cho C. H., Lam Liu E. S., Choy H. T., Wang J. Y., Leung Koo M. W. Antiangiogenic effect of a highly selective cyclooxygenase-2 inhibitor on gastric ulcer healing in rats // Toxicol. Appl. Pharmacol. — 2002. — Vol. 183, N. 1. — P. 41–45.
  16. Habib S. J., Neupert W., Rapaport D. Analysis and prediction of mitochondrial targeting signals // Methods Cell Biol. — 2007. — Vol. 80. — P. 761–781.
  17. Hata A. N., Breyer R. M. Pharmacology and signaling of prostaglandin receptors: Multiple roles in inflammation and immune modulation // Pharmacology & Therapeutics. — 2004. — Vol. 103. — P. 147–166.
  18. Imaeda A. B., Watanabe A., Sohail M. A., Mahmood S., Mohamadnejad M., Sutterwala F. S. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome // J. Clin. Invest. — 2009. — Vol. 119. — P. 305–314.
  19. Jamali F., Lovlin R., Corrigan B. W., Davies N. M., Aberg G. Stereospecific pharmacokinetics and toxicodynamics of ketorolac after oral administration of the racemat and optically pure enantiomers to the rat // Chirality. — 1999. — Vol. 11, N. 3. — P. 201–205.
  20. Kunikata T., Araki H., Takeeda M., Kato S., Takeuchi K. Prostaglandin E prevents indomethacin-induced gastric and intestinal damage through different EP receptor subtypes // J. Physiol. Paris. — 2001. — Vol. 95, N. 1–6. — P.157–163.
  21. Lanas A., Garcia–Rodriguez L. A., Arroyo M. T., Gomollón F., Feu F., González–Pérez A., Zapata E., Bástida G., Rodrigo L., Santolaria S., Güell M., de Argila C. V., Quintero E., Borda F., Piqué J. M. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations // Gut. — 2006. — Vol. 55, N. 12. — P. 1731–1738.
  22. Laporte J. R., Ib áñez L., Vidal X., Vendrell L., Leone R. Upper gastrointestinal bleeding associated with the use of NSAIDs: newer versus older agents // Drug Saf. — 2004. — Vol. 27, N. 6. — P. 411–420.
  23. Lewis A. J., Furst D. W. eds. Nonsteroidal anti– inflammatory drugs: mechanisms and clinical use. — New York: Marcel Dekker, 1987.
  24. Li F., Chordia M. D., Huang T., Macdonald T. L. In vitro nimesulide studies toward understanding idiosyncratic hepatotoxicity: diiminoquinine formation and conjugation // Chem. Res. Toxicol. — 2009. — Vol. 22, N. 1. — P. 72–80.
  25. Liebler D. C., Guengerich F. P. Elucidating mechanisms of drug-induced toxicity // Nat. Rev. Drug Discov. — 2005. — Vol. 4. — P. 410–420.
  26. Lindblom P., Rafter I., Copley C., Andersson U., Hedberg J. J., Berg A. L., Samuelsson A., Hellmold H., Cotgreave I., Glinghammar B. Isoforms of alanine aminotransferase in human tissues and serum-differential tissue expression using novel antibodies // Arch. Biochem. Biophys. — 2007. — Vol. 466, N. 1. — P. 66–77.
  27. Markossian K. A., Golub N. V., Kleymenov S. Y., Muranov K. O., Sholukh M. V., Kurganov B. I. Effect of alpha– crystallin on thermostability of mitochondrial aspartate aminotransferase // Int. J. Biol. Macromol. — 2009. — Vol. 44, N. 5. — P. 441–445.
  28. Mass ó–Gonzákes E. L., Patrignani P., Tacconelli S., García–Rodríguez L. A. Variability among nonsteroidal anti-inflammatory drugs in risk of upper gastrointestinal bleeding // Arthritis Rheum. — 2010. — Vol. 62, N. 6. — P. 1592–1601.
  29. Mattingly J. R., Iriarte A. Jr., Martinez–Carrion M. Structural features which control folding of homologous proteins in cell-free translation systems. The effect of a mitochondrial-targeting presequence on aspartate aminotransferase // J. Biol. Chem. — 1993. — Vol. 268, N. 35. — P. 26320–26327.
  30. Miyazaki M., Rosenblum J. S., Kasahara Y., Nakagawa I., Patricelli M. P. Determination of enzymatic source of alanine aminotransferase activity in serum from dogs with liver injury // J. Pharmacol. Toxicol. Methods. — 2009. — Vol. 60, N. 3. — P. 307–315.
  31. Monteiro J. P., Martins A. F., L úcio M., Reis S., Pinheiro T. J., Geraldes C. F., Oliveira P. J., Jurado A. S. Nimesulide interaction with membrane model systems: Are membrane physical effects involved in nimesulide mitochondrial toxicity? // Toxicol. In Vitro. — 2011. — Vol. 25, N. 6. — P. 1215–1223.
  32. Mózsik G. Approaches to gastrointestinal cytoprotection: from isolated cells, via animal experiments to healthy human subjects and patients with different gastrointestinal disorders // Curr. Pharm. Des. — 2011. — Vol. 17, N. 16. — P. 1556–1572.
  33. Okuda T., Norioka M., Shirata Y., Horie T. Multiple mechanisms underlying troqlitazone-induced mitochondrial permeability transition // Toxicol. Appl. Pharmacol. — 2010. — Vol. 248, N. 3. — P. 242–248.
  34. Rahme E., Bernatsky S. NSAIDs and risk of lower gastrointestinal bleeding // Lancet. — 2010. — Vol. 376, N. 9736. — P. 146–148.
  35. Sherwood P., Lyburn I., Brown S., Ryder S. How are abnormal results for liver function tests dealt with in primary care? // BMJ. — 2001. — Vol. 322, N. 7281. — P. 276–278.
  36. Symposium on Nimesulide: a multifactorial therapeutic approach to the inflammatory process? A 7-year clinical experience. Proceedings of an international congress, Berlin, 1992 // Drugs. — 1993. — Vol.46, Suppl. 1. — P. 1–283.
  37. Wilcox C. M., Alexander L. N., Cotsonis G. A., Clark W. S. Nonsteroidal antiinflammatory drugs are associated with both upper and lower gastrointestinal bleeding // Dig. Dis. Sci. — 1997. — Vol. 42, N. 5. — P. 990–997.
  38. Yang M., Chordia M. D., Li F., Huang T., Linden J., Macdonald T. L. Neutrophil-and myeloperoxidase-mediated metabolism of reduced nimesulide: evidence for bioactivation // Chem. Res. Toxicol. — 2010. — Vol. 23, N. 11. — P. 1691–1700.
  39. Yang R.-Z., Park S., Reagan W. J., Goldstein R., Zhong S., Lawton M., Rajamohan F., Qian K., Liu L., Gong D.-W. Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity // Hepatology. — 2009. — Vol. 49. — N. 2. — P. 598–607.

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Copyright (c) 2012 Proshin S.N., Makarov V.G., Makarova M.N., Kryshen K.L., Kovshin A.V., Samusenko I.A.

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