Comparative effects of indomethacin on hepatic enzymes and histology and on serum indices of liver and kidney function in the rat

M. Falzon, P. H. Whiting, S. W.B. Ewen, A. S. Milton, M. D. Burke

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13 Scopus citations

Abstract

The effects of high-dose indomethacin (three daily doses, 8.5 mg/kg ip) on pathology and histology, on serum and urine biochemistry, and on various hepatic enzyme activities were studied in rats. Hepatic cytochrome P-450 and aminopyrine N-demethylase were decreased by 52-62%, but glucuronyl transferase fell by only 22%. Hepatic glucose-6-phosphatase, aryl esterase, 6-phosphogluconate dehydrogenase and sulphotransferase remained unchanged, while glucose-6-phosphate dehydrogenase increased by 29%. There were no widespread changes in hepatic and renal pathology or histology, but noteworthy was a mild, focal, centrilobular hepatitic response. By contrast, there were severe intestinal lesions: the effects on hepatic enzymes might have been partly a consequence of the intestinal damage. There was a reversible uraemia and significant decreases (20-40% below normal) in both serum albumin and protein, while serum levels of creatinine and aspartate-amino-transferase activity remained constant. A reversible N-acetyl-β-D-glucoseaminidase (NAG) enzymuria occurred (300% above normal), but no significant proteinuria (< 300 mg/l). Administration of 16,16-dimethylprostaglandion F(2α) (0.5 mg/kg iv) concomitantly with the indomethacin greatly ameliorated the intestinal lesions and prevented the decreases in hepatic drug-metabolizing enzymes. Concomitant 16,16-dimethylprostaglandin F(2α) did not, however, influence the indomethacin-induced decreases in serum protein, albumin or NAG-enzymuria. It was concluded that indomethacin had a highly selective effect causing a decrease in hepatic cytochrome P-450, which was not accompanied by severe damage to hepatocyte structure.

Original languageEnglish (US)
Pages (from-to)527-534
Number of pages8
JournalBritish Journal of Experimental Pathology
Volume66
Issue number5
StatePublished - Dec 1 1985
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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