title: The vitamin E derivative, EPC-K1, suppresses inflammation during hepatic ischemia-reperfusion injury and exerts hepatoprotective effects in rats.
abstract: BACKGROUND
  An important component of postoperative management includes alleviation of hepatic ischemia-reperfusion (I/R) injury, which commonly results from liver surgery. EPC-K1 is a hydroxyl radical scavenger reported to have mitigating effects on I/R injury in many organs. This study evaluates the effects of EPC-K1 on hepatic I/R injury.
  
  
  METHODS
  Rats were injected subcutaneously with either EPC-K1 (100 mg/kg) or saline. The hepatic artery and left branch of the portal vein were clamped for 45 min under general anesthesia. Indicators of liver function, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), and of liver tissue damage were evaluated after 6h and 24h of reperfusion. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and high-mobility group box 1 (HMGB1) protein were measured, and apoptosis was quantified via caspase 3/7 activity and TUNEL assay.
  
  
  RESULTS
  AST, ALT, and LDH levels increased significantly as a result of hepatic I/R injury, but were attenuated by EPC-K1 administration. Histologic findings revealed that normal structure of the hepatic parenchyma was maintained in rats pretreated with EPC-K1. TNF-α, IL-6, and HMGB1 levels rose significantly after reperfusion, together with activation of the inflammatory response. However, EPC-K1 administration suppressed levels of inflammatory markers and attenuated the inflammatory response. Moreover, EPC-K1 administration prevented apoptosis as determined by inhibition of caspase 3/7 activity and a decrease in apoptotic cells.
  
  
  CONCLUSIONS
  Results demonstrate that EPC-K1 inhibits the inflammatory response and suppresses apoptosis during hepatic I/R injury. This suggests that EPC-K1 has hepatoprotective effects, and may be a valuable and novel therapeutic agent in the clinical setting.
authors.affiliation: Beppu Medical Center, Beppu City, Oita, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Oishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Satoko
authors.initials: S
authors.lastname: Koga
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawabe
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uno
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D024243:HMGB1 Protein; D007249:Inflammation / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D024243:HMGB1 Protein; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E; C066638:potassium ascorbyl tocopheryl phosphate; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001205:Ascorbic Acid