Nebbia C, Dacasto M, Ceppa L, Gennaro Soffietti M, Spinelli P, Bergo V, Di Simplicio P
Dipartimento di Patologia Animale, Settore di Farmacologia e Tossicologia, Torino, Italy.
Vet Res Commun. 1997 Feb;21(2):117-25. doi: 10.1023/a:1005761302088.
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.
本研究的目的是确定亚慢性（70天）口服中等至高剂量的醋酸三苯基锡（TPTA，一种在全球范围内使用的有机锡衍生物）是否会影响兔和羊的微粒体肝和肾药物代谢酶。给兔提供含0、15、75或150 ppm TPTA的饮食，而给羊每日每千克体重给予0、1.5或7.5 mg TPTA。通过原子吸收分光光度法测量肝脏和肾脏中的锡含量。在兔肝脏中，TPTA未能影响细胞色素P450含量，或所研究的氧化、水解（羧酸酯酶）或结合（UDPG - 转移酶）酶活性。相反，在兔肾脏中检测到P450含量和羧酸酯酶活性均有显著的剂量相关增加（高达280%），但乙氧异吩唑酮脱乙基酶（ECOD）和7 - 乙氧基 - 3 - 异吩唑酮脱乙基酶（EROD）活性分别未改变或略有降低。在所研究的酶中，没有一种在羊肝脏或肾脏亚组分中显示出统计学上的显著变化。结果表明，反复接触TPTA可能导致兔肾脏中一种特定的P450同工酶的诱导，该同工酶与内源性化合物（如类固醇、前列腺素、血栓烷）的代谢有关。锡浓度缺乏显著的组织和物种相关差异支持了这样的假设，即兔肾脏中观察到的变化可能并非仅由金属在组织中的积累引起。
