The comparative effects of subchronic administration of triphenyltin acetate (TPTA) on the hepatic and renal drug-metabolizing enzymes in rabbits and lambs.

摘要

Four groups of 7 rabbits were given diets containing 0, 15, 75 or 150 ppm triphenyltin acetate [fentin acetate] (TPTA), respectively, while 3 groups of four 22- to 30-kg lambs were given a daily oral dose of 0, 1.5 or 7.5 mg TPTA/kg body weight. After 70 days of treatment, the animals were starved over night and killed. The tin content in liver and kidney was measured by atomic absorption spectrophotometry. In the rabbit livers, TPTA did not affect the cytochrome P450 content or the oxidative, hydrolytic (carboxylesterase) or conjugative (UDPG-transferase) enzyme activities investigated. There was a large dose-related increase in both P450 content and carboxylesterase activity (up to 280%) in rabbit kidneys, but the ethoxycoumarin-O-deethylase (ECOD) and ethoxyresorufin-O-deethylase (EROD) activities were, respectively, unchanged or moderately depressed. None of the enzymes studied showed significant changes in ovine liver or kidney subfractions. It is suggested that repeated exposure to TPTA could cause induction of a particular P450-isoenzyme in rabbit kidneys which influences the metabolism of endogenous compounds such as steroids, prostaglandins and thromboxanes. As there were no significant tissue- and species-related differences in the concentration of tin, it is suggested that the changes observed in rabbit kidneys may not be solely attributable to the accumulation of the metal in the tissues.