title: Alpha-lipoic acid attenuates lipopolysaccharide-induced kidney injury.
abstract: BACKGROUND
  Kidney is one of the major target organs in sepsis, while effective prevention of septic acute kidney injury has not yet been established. α-Lipoic acid (LA) has been known to exert beneficial effects against lipopolysaccharide (LPS)-induced damages in various organs such as heart, lung, and liver. We investigated the protective effect of LA on LPS-induced kidney injury.
  
  
  METHODS
  Two groups of rats were treated with LPS (20 mg/kg, i.p.), one of which being co-treated with LA (50 mg/kg), while the control group was treated with vehicle alone. Human renal proximal tubular epithelial cells (HK-2 cells) were cultured with or without LPS (10 μg/ml) in the presence or absence of LA (100 μg/ml) for 3 h prior to LPS treatment.
  
  
  RESULTS
  Serum creatinine level was increased in LPS-treated rats, which was attenuated by LA co-treatment. LPS treatment induced cleaved caspase-3 expression in the kidney, which was counteracted by LA. Terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells increased in the kidneys of LPS-treated rats compared with controls, which was counteracted by LA treatment. Protein expression of inducible nitric oxide synthase and cyclooxygenase-2 detected by immunoblotting and/or immunohistochemical staining, along with mRNA levels of pro-inflammatory cytokines detected by real-time polymerase chain reaction, was increased in the kidney with LPS administration, which was ameliorated with LA treatment. LA also protected LPS-induced tubular dysfunction, preserving type 3 Na(+)/H(+) exchanger and aquaporin 2 expressions in the kidney. Suppression of LPS-induced expression of cleaved caspase-3 by LA was also observed in HK-2 cells. Increased protein expression of phospho-extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases by LPS treatment was attenuated by LA pretreatment, while p38 was not affected by either LPS or LA treatment. MitoTracker Red demonstrated LA prevented LPS-induced increment of mitochondrial oxidative stress, where concurrent 4',6-diamidino-2-phenylindole staining also revealed marked fragmentation and condensation of nuclei in HK-2 cells treated with LPS, which was prevented by LA.
  
  
  CONCLUSIONS
  LA treatment attenuates LPS-induced kidney injury, such as renal tubular dysfunction, by suppression of apoptosis, and inflammation.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, 42 Jebongro, Gwangju, 501-757, Korea.
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Suh
authors.forename: Ko Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: In Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Ok
authors.initials: O
authors.lastname: Kim
authors.forename: Chang Seong
authors.initials: CS
authors.lastname: Kim
authors.forename: Joon Seok
authors.initials: JS
authors.lastname: Choi
authors.forename: Hoon-In
authors.initials: HI
authors.lastname: Choi
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Bae
authors.forename: Seong Kwon
authors.initials: SK
authors.lastname: Ma
authors.forename: Jong Un
authors.initials: JU
authors.lastname: Lee
authors.forename: Soo Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis; D002460:Cell Line; D003404:Creatinine / Q000097:blood; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D007677:Kidney Function Tests; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007473:Ion Channels; D008070:Lipopolysaccharides; D008063:Thioctic Acid; D003404:Creatinine; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3