Toxicity of organotin compounds: IV. Impairment of energy metabolism of rat thymocytes by various dialkyltin compounds

Abstract

Isolated thymocytes were incubated with various carbohydrates in the presence of dimethyltindichloride (DMTC), diethyltindichloride (DETC), di- n-butyltindichloride (DBTC), and di- n-octyltindichloride (DOTC) and the substrate conversion, oxygen consumption, and cell viability were measured. All the dialkyltin compounds produced a dose-dependent stimulation of the glucose consumption, but at different concentrations. The most toxic homologs, DBTC and DETC, stimulated the glucose consumption maximally at levels of 5 and 10 μ m, respectively, whereas DMTC and DOTC were less active, inducing a maximum stimulation at 120 μ m. At higher exposure levels a sharp fall in the stimulation of the glucose consumption was noted together with a decrease of the oxygen consumption and viability of the thymocytes. The oxidative metabolism of glucose, lactate, and pyruvate by the TCA cycle was inhibited by dialkyltin compounds in a dose-related fashion. The glycolytic pathway was not affected, since under anaerobic conditions the glucose consumption was similar to that of the controls up to levels inducing a maximum stimulation of the glucose consumption under aerobic conditions. Probably the entrance of the glycolytic end products into the TCA cyle is disturbed by an inhibition of the pyruvate dehydrogenase system. Additional support for an interference with α-keto acid dehydrogenase complexes were obtained from mitochondrial incubations. DBTC inhibited the pyruvate and α-ketoglutarate conversion, oxygen consumption and ATP production of rat liver mitochondria in a dose-related fashion. Although in vitro the dialkyltin homologs display a comparable mode of action on the energy metabolism of rat thymocytes, in vivo especially DBTC and DOTC induce thymus involution whereas DMTC and DETC hardly decrease thymus weight. This discrepancy may be related with a different distribution pattern of the water-soluble lower homologs and the fat-soluble higher homologs. Therefore, we conclude that the inhibition of the energy metabolism of rat thymocytes by dialkyltins is related to their thymolytic effects in vivo.