Potential mechanism of cadmium-induced cytotoxicity in rat hepatocytes: inhibitory action of cadmium on mitochondrial respiratory activity

Toxicology
T KoizumiK T Suzuki

Abstract

The present study was designed to clarify the mechanism of cadmium (Cd)-induced toxicity in rat hepatocytes. Cd and Mg-ATP induced cellular acidification at concentrations lower than 25 microM. In Mg-ATP-treated cells, maximal acidification occurred within 2.5 min, with a subsequent return to control levels. In Cd-treated cells, maximal acidification (pH 6.76) occurred 10 min after exposure to the metal, then the cytoplasmic pH began to rise but did not return to normal. Cd eliminated the membrane potential of isolated mitochondria in media at both pH 6.5 and 7.4. This effect of Cd on membrane potential was approximately equivalent in both media when the metal concentration was 5 microM, but was more intense in the medium at pH 6.5 than in the medium at pH 7.4 at the metal concentration > 5 microM. Acidic medium alone had no effect on membrane potential. Mitochondrial uptake of Cd increased in a dose-dependent manner in media at both pH 7.4 and 6.5. The uptake of 5 microM Cd was significantly increased by acidic medium, however at Cd concentrations > 5 microM, there were no pH-dependent differences in Cd uptake. The incubation of hepatocytes in the medium at pH 6.0 and 6.5 resulted in 5 and 7.5% inhibition of mitochondrial resp...Continue Reading

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