Cadmium Toxicity and Liver Mitochondria

Abstract

Cadmium chloride (Cd) stimulated state 4 respiration at a concentration as low as 0.3 nmol/mg protein of mitochondria (ca. 0.3 μM) and completely inhibited respiration at a concentration of 10 nmol/mg protein of mitochondria (ca. 10 μM) in isolated rat liver mitochondria. A spectrophotometric study has suggested that one of the interaction sites of Cd in mitochondria is located between the cytochromes b and the substrates, possibly in the flavin region. The sensitivity of mitochondrial respiration to Cd was almost the same in preparations from both adult and young rat livers. It was found that the soluble fraction prepared from the adult rat liver had a protective effect against the Cd-induced inhibition of mitochondrial respiration when the fraction was incubated in the mitochondrial respiratory assay medium. However, the protective effect of the souble fraction prepared from young rat liver was much smaller than that of the fraction obtained from adult rat liver. It is thus suggested that the interaction of Cd with liver soluble protein(s) is important for minimizing the Cd toxicity to mitochondria, and that differences in the protective effect of the liver soluble fraction might be responsible for the different sensitivities to Cd toxicity of adult and young rat livers, which was reported in the preceding paper (Sato, N. et al. (1978) J. Biochem. 84, 117–125). The protective effect of the liver soluble fraction prepared from young rat (31 days old) became more apparent upon prior treatment of the young rats with spironolactone (0.12 g/kg body weight)