title: Protective effects of apocynin and allopurinol on ischemia/reperfusion-induced liver injury in mice.
abstract: OBJECTIVE
  To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice.
  
  
  METHODS
  Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion.
  
  
  RESULTS
  A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-alpha levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure.
  
  
  CONCLUSIONS
  Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generation of superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.
authors.affiliation: UC Davis Medical Center, Transplant Research Institute, 4635 2nd Ave. Suite 1001, Sacramento, CA 95817, USA.
authors.forename: Ping-Guo
authors.initials: PG
authors.lastname: Liu
authors.forename: Song-Qing
authors.initials: SQ
authors.lastname: He
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D052096:Warm Ischemia / Q000009:adverse effects; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D008315:Malondialdehyde; D000493:Allopurinol; C056165:acetovanillone; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D005978:Glutathione