Effects of Wy14643 on hepatic ischemia reperfusion injury in rats.
OBJECTIVE
To investigate the effects and possible mechanisms of Wy14643 on hepatic ischemia-reperfusion (I/R) injury in rats.


METHODS
Thirty male Sprague-Dawley rats weighing 220-280 g were randomly divided into five experimental groups: sham group (G1, n=6): a sham operation was performed (except for liver I/R); I/R-untreated group (G2, n=6): rats underwent liver ischemia for 90 min followed by reperfusion for 4 h; and I/R+Wy14643 groups (G3, G4, G5; n=6): after the same surgical procedure as in group 2, animals were pretreated with Wy14643 at the dose of 1, 5 and 10 mg/kg 1 h before ischemia, respectively. Hepatic ischemia-reperfusion (I/R) was induced by clamping blood supply to the left lateral and median lobes of the liver for 90 min, and atraumatic clamp was removed for 4 h reperfusion. Blood samples and liver tissues were obtained at the end of reperfusion to assess serum and hepatic tissue homogenate aminotransferase (ALT), aspartate aminotransferase (AST), myeloperoxidase (MPO), serum interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), as well as activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the hepatic tissue homogenate.


RESULTS
Hepatic I/R induced a significant increase in the serum levels of ALT, AST, TNF-alpha, IL-1beta and MPO, as well as the levels of ALT, AST and MDA in the liver tissue homogenate, which were reduced by pretreatment with Wy14643 at the dose of 1, 5 and 10 mg/kg, respectively. The activity of SOD in the liver tissue homogenate was decreased after hepatic I/R, which was enhanced by Wy14643 pretreatment. In addition, serum and liver tissue homogenate ALT and AST in the Wy14643 10 mg/kg group were lower than in the Wy14643 1 mg/kg and 5 mg/kg groups, respectively.


CONCLUSIONS
Wy14643 pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of anti-oxidant and inhibition inflammation response.
Xu
Si-Qi
SQ
Department of Anesthesiology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China.
Li
Yuan-Hai
YH
Hu
Sheng-Hong
SH
Chen
Ke
K
Dong
Liu-Yi
LY
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D004195:Disease Models, Animal; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists*; D009195:Peroxidase / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D053583:Interleukin-1beta; D047493:PPAR alpha; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; C006253:pirinixic acid; D009195:Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase