Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation

Background. Cisplatin is a chemotherapeutic agent used in treatment of malignant tumours. However, cisplatin produces various side effects, such as nephrotoxicity, neurotoxicity, emetogenesis and ototoxicity. Inflammation is an important mechanism of cisplatin nephrotoxicity. Alpha-lipoic acid (α-LA) has anti-inflammatory effects that inhibit both adhesion molecule expression in human endothelial cells and monocyte adhesion by suppressing the nuclear factor-κB (NF-κB) signalling pathway. The goals of this study were to investigate the anti-inflammatory effects of α-LA during cisplatin-induced renal injury and to examine the mechanisms of protection.Methods. C57BL6 mice were given cisplatin (20 mgkg) with or without α-LA treatment (100 mgkg for 3 days). Renal function, histological changes, adhesion molecule expression and inflammatory cell infiltration were examined. The effect of α-LA on NF-κB activity was evaluated by examining nuclear translocation and phosphorylation of NF-κB p65 subunits in kidney tissue.Results. Cisplatin-induced decreases in renal function, measured by blood urea nitrogen, serum creatinine level and renal tubular injury scores, were attenuated by α-LA treatment. α-LA decreased the tissue levels of tumour necrosis factor-α, the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and suppressed the infiltration of CD11b-positive macrophages. α-LA also attenuated the cisplatin-induced increases in the phosphorylation and nuclear translocation of NF- κB p65 subunits in kidney tissue.Conclusions. These results suggest that α-LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-κB activity.