On the oxidative damage by cadmium to kidney mitochondrial functions

Abstract

In the kidney, the accumulation of heavy metals such as Cd²⁺ produces mitochondrial dysfunctions, i.e., uncoupling of the oxidative phosphorylation, inhibition of the electron transport through the respiratory chain, and collapse of the transmembrane electrical gradient. This derangement may be due to the fact that Cd²⁺ induces the transition of membrane permeability from selective to nonselective via the opening of a transmembrane pore. In fact, Cd²⁺ produces this injury through the stimulation of oxygen-derived radical generation, inducing oxidative stress. Several molecules have been used to avoid or even reverse Cd²⁺-induced mitochondrial injury, for instance, cyclosporin A, resveratrol, dithiocarbamates, and even EDTA. The aim of this study was to explore the possibility that the antioxidant tamoxifen could protect mitochondria from the deleterious effects of Cd²⁺. Our results indicate that the addition of 1 μmol/L Cd²⁺ to mitochondria collapsed the transmembrane electrical gradient, induced the release of cytochrome c, and increased both the generation of H₂O₂ and the oxidative damage to mitochondrial DNA (among other measured parameters). Of interest, these mitochondrial dysfunctions were ameliorated after the addition of tamoxifen.

Keywords: cadmium; kidney; mitochondria; mitochondrie; oxidative stress; permeability transition; rein; stress oxydant; transition de perméabilité.