Efficacy of alpha-lipoic acid against cadmium toxicity on metal ion and oxidative imbalance, and expression of metallothionein and antioxidant genes in rabbit brain

摘要

To explore the protective efficacy of alpha-lipoic acid (ALA) against Cd-prompted neurotoxicity, young male New Zealand rabbits (Oryctolagus cuniculus) were divided randomly into four groups. Group 1 (control) received demineralized water. Group 2 (Cd) administered cadmium chloride (CdCl2) 3 mg/kg bwt. Group 3 (ALA) administered ALA 100 mg/kg bwt. Group 4 (Cd + ALA) administered ALA 1 h after Cd. The treatments were administered orally for 30 consecutive days. Cd-induced marked disturbances in neurochemical parameters were indicated by the reduction in micro- and macro-elements (Zn, Fe, Cu, P, and Ca), with the highest reduction in Cd-exposed rabbits, followed by Cd + ALA group and then ALA group. In the brain tissues, Cd has significantly augmented the lipid hydroperoxides (LPO) and reduced the glutathione (GSH) and total antioxidant capacity (TAC), and glutathione peroxidase and glutathione S-transferase enzyme activities but had an insignificant effect on the antioxidant redox enzymes. Administration of ALA effectively restored LPO and sustained GSH and TAC contents. Moreover, Cd downregulated the transcriptional levels of Nrf2, MT3, and SOD1 genes, and upregulated that of Keap1 gene. ALA treatment, shortly following Cd exposure, downregulated Keap1, and upregulated Nrf2 and GPx1, while maintained MT3 and SOD1 mRNA gene expression in the rabbits' brain. These data indicated the ALA effectiveness in protecting against Cd-induced oxidative stress and the depletion of cellular antioxidants in the brain of rabbits perhaps due to its antioxidant, free radical scavenging, and chelating properties.