Cytochrome P-450-dependent biotransformation in Uje:WIST rats with chronic liver injury induced by thioacetamide.

Abstract

In female Uje:WIST rats micronodular liver cirrhosis was produced by thioacetamide (TAA) given in the drinking water (0.3 g/l) from the 4th to 6th months of life. 14 d after TAA cessation it was examined, whether this animal model reflects the restricted cytochrome P-450-dependent biotransformation in severe stages of human liver cirrhosis by in vivo (caffeine and metamizol elimination) and in vitro methods (cytochrome P-450, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylation, ethylmorphine N-demethylation). The total biotransformation capacity was unchanged in TAA rats, partly even enhanced. Only several in vitro parameters reflect diminished cytochrome P-450-dependent biotransformation calculated per weight unit comparable to severe stages of human liver cirrhosis. Therefore, the chosen experimental conditions are suitable for conclusions concerning cytochrome P-450-dependent biotransformation in early rather than in severe stages of human liver cirrhosis.