title: Alpha-lipoic acid attenuates cisplatin-induced tubulointerstitial injuries through inhibition of mitochondrial bax translocation in rats.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Lee
authors.forename: So Yon
authors.initials: SY
authors.lastname: Bae
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Won
authors.forename: Heui Jung
authors.initials: HJ
authors.lastname: Pyo
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Kwon
mesh_terms: 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*
chemical_list: D000975:Antioxidants; D051028:bcl-2-Associated X Protein; D008063:Thioctic Acid; D012964:Sodium; D003404:Creatinine; D053148:Caspase 3; D053453:Caspase 9; D002945:Cisplatin