Protective effects of apocynin and allopurinol on ischemia/reperfusion-induced liver injury in mice.
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.
Liu
Ping-Guo
PG
UC Davis Medical Center, Transplant Research Institute, 4635 2nd Ave. Suite 1001, Sacramento, CA 95817, USA.
He
Song-Qing
SQ
Zhang
Yan-Hong
YH
Wu
Jian
J
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
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