Summary
Indomethacin was parenterally administered (6 mg/Kg/day) for 30 days to rabbits, to evaluate changes in serum biochemical parameters and any ultrastructural alterations induced by the drug at the hepatic level. An analysis of the results demonstrated that when the group of rabbits treated with indomethacin was compared to a control group of healthy non-treated rabbits, a statistically significant increase in the serum ALT was found in the treated rabbits. Ultrastructural observations showed the following hepatocyte alterations: 1) minimum mitochondrial alterations 2) mild signs of cholestasis (pericanalicular osmophilic bodies) 3) Smooth endoplasmic reticulum hyperplasia. These findings suggest that indomethacin has the capacity to induce hepatic lesions in the rabbit and this is probably due to the surfactant mechanism.
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References
Flower, R.J., Moncada, S., Vane, J.R. Analgesic, antipiretic and anti-inflammatory agents. The Pharmacological Basis of Therapeutics, 7th Edition, Edited by Goodman and Gilman, 1985, 674–715.
Fenech, F.F., Bannister, W.H., Grech, J L Hepatitis with biliverdinemia in association with indomethacin therapy. Br Med J 1967, 2, 155–156.
Kelsey, W.M., Schary, J.M.: Fatal hepatitis probably due to indomethacin. JAMA 1967, 199, 586–587.
Martines, G., “Reportage ultrastrutturale delle disepatie”. Italo Bovolenta, Editore, Bologna, 1982.
Byczkowski, J.Z., Korolkiewicz, K.Z. The sites of action of indomethacin in rat liver mitochondria. Pharmacol Res Commun 1977, 9, 259–268.
Schaffner, F., Popper, H. “Classification and mechanism of cholestasis,” In: Liver and biliary disease, 2 Edition. Edited by Wright R., Millward-Sadler G.H., Alberti, K.G.M.M., Karran, S., Baillere Tindall, W.B., Saunders Company, 1985, 359–386.
Falzon, M., Nielsch, A., Burke, M.D. Denaturation of cytochrome P-450 by indomethacin and other nonsteroidal anti-inflammatory drugs: evidence for a surfactant mechanism and a selective effect of a p-clorophenil moiety. Biochem Pharmacol 1986, 35, 4019–4024.
Schaffner, F., “Some unresolved ultrastructural problems encountered in the study of liver and its disease”. In: The liver and its diseases, Edited by Schaffner F, Sherlock, S., Leevy C.M., George Thieme Publ., Stuttgart, New York, 1974, 7–18.
Falzon, M., Whiting, P.H., Ewen, S.W.B., Milton, A.S., Burke, M.D. Comparative effects of indomethacin on hepatic enzymes and histology and on serum indices of liver and kidney function in the rat. Br J Exp Pathol 1985, 66, 527–534.
Harman, R.E., Meisinger, M.A.P., Davis, G.E., Kuehel, F.A. The metabolites of indomethacin, a new anti-inflammatory drug. J Pharmacol Exp Ther 1964, 143, 215–220.
Hucker, H.B., Zacchei, A.G., Cox, S.V., Brodie, D.A., Cantwell, N.H.R.: Studies on the absorption, distribution and excretion of indomethacin in various species. J Pharmacol Exp Ther 1966, 153, 237–249.
Rainsford, K.D., Schweitzer, A., Brune, K. Autoradiographic and biochemical observations on the distribution of nonsteroid anti-inflammatory drugs. Arch Int Pharmacodyn 1981, 250, 180–194.
Codley, E.L., Enzyme diagnosis in hepatic disease. Am J Gastroenterol 1971, 56, 413–419.
Winkel, P. Romsoe, K., Lynghye, T., Tygstrup, N. Diagnostic value of routine liver function test. Clin Chem 1975, 21, 71–75.
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Martines, G., Boiardi, L., Butturini, L. et al. Hepatic alterations in indomethacin-treated rabbits. Clin Rheumatol 7, 24–27 (1988). https://doi.org/10.1007/BF02284052
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DOI: https://doi.org/10.1007/BF02284052