THE COMPARATIVE EFFECTS OF SUBCHRONIC ADMINISTRATION OF TRIPHENYLTIN ACETATE (TPTA) ON THE HEPATIC AND RENAL DRUG-METABOLIZING-ENZYMES IN RABBITS AND LAMBS

The purpose of this study was to determine whether subchronic (70 days ) oral exposure to moderate to high levels of triphenyltin acetate (TP TA), an organotin derivative used worldwide, would affect the microsom al hepatic and renal drug-metabolizing enzymes in rabbits and lambs. R abbits were offered a diet containing 0, 15, 75 or 150 ppm TPTA, while lambs were daily given 0, 1.5 or 7.5 mg TPTA per kg bw. The tin conte nt in the liver and kidneys was measured by atomic absorption spectrop hotometry. In the rabbits' livers, TPTA failed to affect the cytochrom e P450 content, or the oxidative, hydrolytic (carboxylesterase) or con jugative (UDPG-transferase) enzyme activities studied. In contrast, a striking dose-related increase in both P450 content and carboxylestera se activity (up to 280%) was detected in the rabbits' kidneys, but the ECOD and EROD activities were respectively unchanged or moderately de pressed. None of the enzymes studied showed statistically significant changes in the ovine hepatic or renal subfractions. The results sugges t that repeated exposure to TPTA could lead to the induction of a part icular P450-isoenzyme in rabbit kidneys which is concerned with the me tabolism of endogenous compounds (e.g. steroids, prostaglandins, throm boxanes). The lack of significant tissue- and species-related differen ces in the concentration of tin supports the hypothesis that the chang es observed in the rabbits' kidneys may not have been caused solely by the accumulation of the metal in the tissues.