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

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

Research output: Contribution to journalArticle

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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 - 1985
Externally publishedYes

Fingerprint

Indomethacin
Histology
Kidney
Liver
Enzymes
Serum
Transferases
Serum Albumin
Cytochrome P-450 Enzyme System
Blood Proteins
Aminopyrine N-Demethylase
Phosphogluconate Dehydrogenase
Pathology
Sulfotransferases
Glucose-6-Phosphatase
Glucosephosphate Dehydrogenase
Uremia
Esterases
Proteinuria
Aspartic Acid

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Comparative effects of indomethacin on hepatic enzymes and histology and on serum indices of liver and kidney function in the rat. / Falzon, Miriam; Whiting, P. H.; Ewen, S. W B; Milton, A. S.; Burke, M. D.

In: British Journal of Experimental Pathology, Vol. 66, No. 5, 1985, p. 527-534.

Research output: Contribution to journalArticle

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