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 effects of oral subchronic exposure (70 d) to triphenyltin acetate (TPTA) on hepatic and renal enzymes involved in glutathione metabolism were investigated in rabbits and lambs. Rabbits were offered a diet fortified with 15, 75 or 150 ppm TPTA, whereas lambs were daily given 1 or 7.5 mg/kg TPTA On the whole, rabbits were more susceptible than lambs and in both species hepatic enzymes were affected to a greater extent than renal enzymes. In rabbit liver, glutathione S-transferase activity toward 1,2-dichloro-4-nitrobenzene (DCNB) was enhanced at 15 ppm and depressed at 150 ppm TPTA, whereas selenium-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 activities in rabbits, only GPX activity was significantly inhibited at 150 ppm TPTA. The only statistically significant changes in lambs were a fall in both hepatic GST accepting DCNB as substrate at 7.5 mg/kg and Se-GPX at 1 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 GST and GPX are part of the complex mechanism of organotin toxicity.
De Simplicio
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Istituto di Clinica delle Malattie Nervose e Mentali, Sezione di Farmacologia, Università di Siena, Italy.
Dacasto
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Carletti
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Giannerini
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Nebbia
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D000818:Animals; D054477:Glutaredoxins; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000032:analysis; D005980:Glutathione Reductase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D007674:Kidney Diseases / Q000201:enzymology*; D008107:Liver Diseases / Q000201:enzymology*; D009947:Organotin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D010088:Oxidoreductases; D011506:Proteins / Q000032:analysis; D011817:Rabbits; D011897:Random Allocation; D012756:Sheep; D012757:Sheep Diseases / Q000201:enzymology*; D013869:Thiolester Hydrolases / Q000032:analysis; D000099301:Hydroxyacylglutathione Hydrolase
D054477:Glutaredoxins; D005978:Glutathione; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D009947:Organotin Compounds; D010088:Oxidoreductases; D011506:Proteins; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase; C030665:triphenyltin