Changes in hepatic and renal glutathione-dependent enzyme activities in rabbits and lambs subchronically treated with triphenyltin acetate

To gain insight into the biochemical mechanisms of organotin toxicity the e ffects of oral subchronic exposure (70 d) to triphenyltin acetate (TPTA) on hepatic and renal enzymes involved in glutathione metabolism were investig ated in rabbits and lambs. Rabbits were offered a diet fortified with 15, 7 5 or 150 ppm TPTA, whereas lambs were daily given 1 or 7.5 mg/kg TPTA. On t he whole, rabbits were more susceptible than lambs and in both species hepa tic enzymes were affected to a greater extent than renal enzymes. In rabbit liver, glutathione S-transferase activity toward 1.2-dichloro-4-nitrobenze ne (DCNB) was enhanced at 15 ppm and depressed at 150 ppm TPTA, whereas sel enium-dependent glutathione peroxidase (Se-GPX) decreased in a dose-related manner; glyoxalase II (GII) activity increased to the same extent at 15 or 75 ppm TPTA but was unaffected at 150 ppm TPTA. For renal enzyme activitie s in rabbits, only GPX activity was significantly inhibited at 150 ppm TPTA . The only statistically significant changes in lambs were a fall in both h epatic GST accepting DCNB as substrate at 7.5 mg/kg and Se-GPX at I or 7.5 mg/kg TPTA, and an increase in renal GII activity at 7.5 mg/kg TPTA. These results suggest that depression of important antioxidant enzymes such as GS T and GPX are part of the complex mechanism of organotin toxicity.