Toxicity of cadmium to renal mitochondria when administered in vivo and in vitro

Abstract The effect of Cd 2+ on energy-linked functions of rat kidney cortex mitochondria was studied after in vivo administration as well as when the metal was added in vitro. In vitro Cd at concentrations below 5 μ m had no effects on mitochondrial energy coupling nor on coupled or uncoupled respiration. Ca 2+ uptake by the mitochondria was inhibited whether Cd was added during or before the addition of Ca 2+ . The inhibition was mainly competitive as judged by Dixon plots, with an apparent K i of approximately 1.6 μ m . In in vivo experiments the rats were exposed to 4 m m Cd in their drinking water for 6 weeks. During this time the accumulation of Cd in the tissues was extensive. The weight of treated rats was slightly decreased in comparison to control animals. However, mitochondria from treated rats showed no inhibition of Ca 2+ uptake while the other energy-linked functions were affected to some degree by the Cd treatment. These differences in the effects of Cd despite the similar amounts present in in vivo and in vitro conditions may be due to Cd being bound in an unreactive form in the kidney mitochondria of treated rats. The effects of Cd on the energy-linked functions in these mitochondria may be secondary to other changes that the metal causes in kidney metabolism rather than due to direct effects of Cd on mitochondria.