The metabolism and toxicity of some organotin compounds in isolated rat hepatocytes

Abstract

The metabolism and toxicity of some ethyl-substituted organotin compounds in isolated rat hepatocytes were studied. Tetra- and triethyltin derivatives were metabolized by isolated rat hepatocytes to yield ethane and ethylene. Hydrocarbon formation from tetraethyltin was larger than that obtained with triethyltin bromide, and ethylene was the major product (95%) of tetraethyltin metabolism. At a triethyltin salt concentration of 100 μM, the major product formed by cells from untreated rats was ethane. Pretreatment in vivo by phenobarbital resulted in a marked increase in the overall rate of hydrocarbon production and a change in ethylene to ethane ratio; in this case ethylene was the predominant metabolite produced. 5,6-Benzoflavone pretreatment in vivo resulted in a small depression in overall hydrocarbon production. No metabolism of diethyltin dichloride (100 μM) by isolated rat heptocytes was detected. Triethyltin bromide (100 μM) was a potent inhibitor of both the Phase I (oxidation) and Phase II (conjugation) metabolism of biphenyl in isolated hepatocytes from phenobarbital-pretreated rats, whereas diethyltin dichloride was seen to affect particularly the Phase I metabolism of the aromatic hydrocarbon. Triethyl- and diethyltin salts reduced oxygen consumption and ATP levels in these cells. However, the triethyl derivative was more effective in this respect. Tetraethyltin was not appreciably toxic to hepatocytes. Trypan blue dye exclusion and lactate dehydrogenase loss by the cells isolated from phenobarbital-pretreated rats indicated that triethyltin bromide was more toxic than diethyltin dichloride. In contrast, the diethyl derivative was more potent in stimulating lipid peroxidation as indicated by formation of thiobarbituric acid-reactive products than was triethyltin.