Alpha-Lipoic Acid Attenuates Cisplatin-lnduced Tubulointerstitial Injuries through Inhibition of Mitochondrial Bax Translocation in Rats

摘要

Background: Renal tubule cell apoptosis plays a pivotal role in cisplatin-induced nephrotoxicity. a-Lipoic acid (LA), a thi-ol antioxidant, is well known to be cytoprotective in various cell death models through its involvement in the death receptor apoptosis pathway. However, we hypothesized that LA would attenuate cisplatin-induced nephrotoxicity through inhibition of mitochondrial bax translocation in rats. Methods and Materials: Sprague-Dawley rats were treated with cisplatin (7 mg/kg) with or without pretreatment with LA (100 mg/kg X 3 times). Renal function was evaluated based on blood urea nitrogen (BUN), serum cre-atinine, and fractional excretion of sodium. Tubular necrosis scores were assessed by light microscopy findings and apop-totic cell deaths by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Cytosolic bax, mitochondrial bax, cytochrome c, caspase-9 and cas-pase-3 were investigated using Western blot in each group. Results: LA pretreatment significantly decreased both BUN and serum creatinine. Morphologically, both tubular necrosis and apoptosis of tubular cells were decreased significant-ly with LA pretreatment. LA attenuated the translocation of mitochondrial bax, reduced the release of cytochrome c, and decreased the expression of caspase-3 and caspase-9 serially in cisplatin nephrotoxicity. Conclusion: We demonstrated that LA attenuates cisplatin-induced renal tubular damages by inhibition of mitochondrial bax translocation inViVO.