Alpha-lipoic acid attenuates cisplatin-induced tubulointerstitial injuries through inhibition of mitochondrial bax translocation in rats.
BACKGROUND
Renal tubule cell apoptosis plays a pivotal role in cisplatin-induced nephrotoxicity. alpha-Lipoic acid (LA), a thiol 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
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 creatinine, and fractional excretion of sodium. Tubular necrosis scores were assessed by light microscopy findings and apoptotic cell deaths by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Cytosolic bax, mitochondrial bax, cytochrome c, caspase-9 and caspase-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 significantly 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.


CONCLUSIONS
We demonstrated that LA attenuates cisplatin-induced renal tubular damages by inhibition of mitochondrial bax translocation in vivo.
Lee
Young Mo
YM
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Bae
So Yon
SY
Won
Nam Hee
NH
Pyo
Heui Jung
HJ
Kwon
Young Joo
YJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009336:Necrosis; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D008063:Thioctic Acid / Q000494:pharmacology*; D014178:Translocation, Genetic / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D051028:bcl-2-Associated X Protein; D008063:Thioctic Acid; D012964:Sodium; D003404:Creatinine; D053148:Caspase 3; D053453:Caspase 9; D002945:Cisplatin