Hepatotoxicity Studies of Nimesulide in Litters of Rat
Hepatotoxicity Studies of Nimesulide in Litters of Rat
Keywords:
Nimesulide, Hepatotoxicity, Histopathology of liver, Serum glutamate oxaloacetate transaminase, Serum glutamate pyruvate transaminase, Alkaline phosphataseAbstract
Present study was carried out to evaluate hepatotoxicity of nimesulide by single dose and seven days administration in sub therapeutic, therapeutic and supra therapeutic doses in litters of rat. Single dose and seven days administration hepatotoxicity studies of nimesulide were carried out in litters of rat of either sex. They were further subdivided into sub therapeutic (20 mg/kg), therapeutic (30 mg/kg) and supra therapeutic (100 mg/kg) groups. Effect of nimesulide on liver functions were analysed by serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and histopathological examination of liver through scoring system. Histopathological changes in liver were observed in therapeutic and supra therapeutic doses in single dose groups and sub therapeutic, therapeutic and supra therapeutic doses in seven days groups. In single dose of nimesulide in litters, there were significant increases in biochemical parameters (p< 0.05) in supratherapeutic doses. However, in seven days studies of nimesulide in litters, there were significant increases in biochemical parameters (p< 0.05) in therapeutic and supratherapeutic doses. The present study indicates that nimesulide causes significant hepatotoxicity in litters of rat.
References
2. Giuliano F, Ferraz JG, Pereira R, et al. Cyclooxygenase selectivity of non-steroidal anti-inflammatory drugs in humans: ex vivo evaluation. Eur J Pharmacol 2001;426:95-103.
3. Famaey JP. In vitro and in vivo pharmacological evidence of selective cyclooxygenase-2 by nimesulide: An overview. Inflamm Res 1997;46:437-46.
4. Tan HH, Ong WM, Lai SH, et al. Nimesulide-induced hepatotoxicity and fatal hepatic failure. Singapore Med J 2007;48:586.
5. Chatterjee S, Pal J, Biswas N. Nimesulide-induced hepatitis and toxic epidermal necrolysis. J Postgrad Med 2008;54:150-1.
6. Van Steenbergen W, Peeters P, De Bondt J, et al. Nimesulide-induced acute hepatitis: evidence from six cases. J Hepatol 1998;29:135-41.
7. Merlani G, Fox M, Oehen HP, et al. Fatal hepatoxicity secondary to nimesulide. Eur J Clin Pharmacol 2001;57:321-6.
8. Papaioannides D, Korantzopoulos P, Athanassiou E, et al. Nimesulide-induced acute hepatotoxicity. Ind J Gastroentero 2003;22:239.
9. Gallelli L, Ferraro M, Mauro GF, et al. Nimesulide-Induced Hepatotoxicity in a Previously Healthy Woman. Clin Drug Investig 2005;25:421-424.
10. Aithal GP, Day CP. Nonsteroidal anti-inflammatory drug-induced hepatotoxicity. Clin Liver Dis 2007;11:563-75.
11. Bernareggi A. Clinical pharmacokinetics of nimesulide. Clin Pharmacokinet 1998;35:247-274.
12. Weiss P, Mouallem M, Bruck R, et al. Nimesulide-induced hepatitis and acute liver failure. Isr Med Assoc J 1999;1:221.
13. Schattnu A, Sokolovskya N, Cohen J. Fatal hepatitis and renal failure during treatment with Nimesulide. J Int Med 2000;247:153-55.
14. Rodrigo L, de Francisco R, Pérez-Pariente JM, et al. Nimesulide-induced severe hemolytic anemia and acute liver failure leading to liver transplantation. Scand J Gastroenterol 2002;37:1341-3.
15. Orhan O, Arif H, Sami SK, et al. Nimesulide-induced fulminant hepatitis. Turk J Gastroenterol 2003;14:208-10.
16. Walker SL, Kennedy F, Niamh N, et al. Nimesulide associated fulminant hepatic failure. Pharmacoepidemiol Drug Saf 2008;17:1108-12.
17. Thawani V, Sontakke K, Gharpe K, et al. Nimesulide: The current controversy. Indian J Pharmacol 2003;35:121-22.18. Salmòn Rodriguez LE, Arista Viveros HA, Lujan ME, et al. Assessment of the efficacy and safety of nimesulide vs naproxen in paediatric patients with respiratory tract infections. A comparative single-blind study. Drugs 1993;46 Suppl 1:226-30.
19. Salzberg R, Giambonini S, Maurizio M, et al. A double-blind comparison of nimesulide and mefenamic acid in the treatment of acute upper respiratory tract infections in children. Drugs 1993;46 Suppl 1:208-11.
20. Gianiorio P, Zappa R, Sacco O, et al. Antipyretic and anti-inflammatory efficacy of nimesulide vs paracetamol in the symptomatic treatment of acute respiratory infections in children. Drugs 1993;46 Suppl 1:204-7.
21. Gupta P, Sachdev H P. Safety of oral use of nimesulide in children: systematic review of randomized controlled trials. Indian Pediatrics 2003;40:518-531.
22. Ghosh MN. Fundamentals of Experimental Pharmacology. Kolkata: Hilton & Company, 2008.
23. Bergmeyer HU, Horder M, Rej R. IFCC methods for the measurements of catalytic concentrations of enzymes. J Clin Chem Biochem 1986;24:481.
24. Teitz NW, Rinker ADU, Shaw LM. IFCC methods for the measurement of catalytic concentration of enzymes. Part 5. IFCC method for alkaline phosphatise. J Clin Chem Biochem 1983;21:371- 478.
25. Galigher AE, Kozloff EN. Essentials of practicle microtechnique. 2nd ed. Philadelphia. Lea and Febriger; 1971. p.77.
26. Tay VK, Wang AS, Leow KY, et al. Mitochondrial permeability transition as a source of superoxide anion induced by the nitroaromatic drug nimesulide in vitro. Free Radic Biol Med 2005;39:949-59.
27. Ong MM, Wang AS, Leow KY, et al. Nimesulide-induced hepatic mitochondrial injury in heterozygous Sod2(+/-) mice. Free Radic Biol Med 2006;40:420-9.
28. Mingatto FE, Rodrigues T, Pigoso AA, et al. The critical role of mitochondrial energetic impairment in the toxicity of nimesulide to
hepatocytes. J Pharmacol Exp Ther 2002;303:601-7.
29. Bernareggi A. Clinical pharmacokinetics of nimesulide. Clin Pharmacokinet 1998;35:247-27
