Alpha lipoic acid attenuates cadmium-induced nephrotoxicity via the mitochondrial apoptotic pathways in rat

Alpha lipoic acid (alpha-LA), a potent antioxidant, is protective against acute nephrotoxicity. In the present study, the attenuation of cadmium (Cd)-induced kidney injury by alpha-LA on was investigated in a rat model. Exposure to 50 mg/L Cd for 12 weeks increased kidney index and Cd content, malondialdehyde (MDA) levels, and histolo-gical damage to the renal cortex, and decreased the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Treatment with 50 mg/L Cd also damaged renal cell mitochondria and nuclei, and activated the mitochondrial apoptosis pathway, indicated by increased gene and protein expression/activation of caspase-9, caspase-3, poly ADP-ribose polymerase (PARP) and Bc1-2 adenovirus El a nineteen kilodalton interacting protein 3 (BNIP3), and translocation of cytochrome c (cyt c), apoptosis-inducing factor (AIF), and endonuclease G (Endo G). However, simultaneous supplementation with a-LA (50 mg/kg.bw) protected kidney cells from Cd-induced cytotoxicity by reducing MDA levels and Cd content, restoring endogenous enzyme activities, renewing mitochondrial function, and preventing activation of the mitochondria apoptosis pathway.