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 (TPTA), an organotin derivative used worldwide, would affect the microsomal hepatic and renal drug-metabolizing enzymes in rabbits and lambs. Rabbits 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 content in the liver and kidneys was measured by atomic absorption spectrophotometry. In the rabbits' livers, TPTA failed to affect the cytochrome P450 content, or the oxidative, hydrolytic (carboxylesterase) or conjugative (UDPG-transferase) enzyme activities studied. In contrast, a striking dose-related increase in both P450 content and carboxylesterase activity (up to 280%) was detected in the rabbits' kidneys, but the ECOD and EROD activities were respectively unchanged or moderately depressed. None of the enzymes studied showed statistically significant changes in the ovine hepatic or renal subfractions. The results suggest that repeated exposure to TPTA could lead to the induction of a particular P450-isoenzyme in rabbit kidneys which is concerned with the metabolism of endogenous compounds (e.g. steroids, prostaglandins, thromboxanes). The lack of significant tissue- and species-related differences in the concentration of tin supports the hypothesis that the changes observed in the rabbits' kidneys may not have been caused solely by the accumulation of the metal in the tissues.
Nebbia
C
C
Dipartimento di Patologia Animale, Settore di Farmacologia e Tossicologia, Torino, Italy.
Dacasto
M
M
Ceppa
L
L
Gennaro Soffietti
M
M
Spinelli
P
P
Bergo
V
V
Di Simplicio
P
P
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000284:Administration, Oral; D000704:Analysis of Variance; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000493:pharmacokinetics / Q000633:toxicity; D014453:Glucuronosyltransferase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009928:Organ Specificity; D009947:Organotin Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D011817:Rabbits; D012756:Sheep; D013054:Spectrophotometry, Atomic; D014001:Tin / Q000032:analysis
D005659:Fungicides, Industrial; D009947:Organotin Compounds; C011978:phentin acetate; D014001:Tin; D003577:Cytochrome P-450 Enzyme System; D015660:7-Alkoxycoumarin O-Dealkylase; D000815:Aniline Hydroxylase; D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase