Role of Akt-dependent up-regulation of hemeoxygenase-1 in resveratrol-mediated attenuation of hepatic injury after trauma hemorrhage.
BACKGROUND
Protein kinase B (Akt) is known to be involved in pro-inflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of hemeoxygenase (HO)-1, which exerts potent anti-inflammatory effects. The aim of this study is to elucidate whether Akt/HO-1 plays any role in resveratrol-mediated attenuation of hepatic injury after trauma hemorrhage.


METHODS
Male Sprague-Dawley rats were subjected to trauma hemorrhage. A single dose of resveratrol (30-mg/kg body weight) with or without a PI3 K inhibitor (wortmannin) or an HO antagonist (chromium-mesoporphyrin) was administered intravenously during resuscitation. Various parameters were measured at 24 hours postresuscitation.


RESULTS
Results showed that trauma hemorrhage increased hepatic myeloperoxidase activity, cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1, and interleukin-6 levels and plasma aspartate and alanine aminotransferases concentrations. These parameters were significantly improved in the resveratrol-treated rats subjected to trauma hemorrhage. Resveratrol treatment also increased hepatic Akt activation and HO-1 expression as compared with vehicle-treated trauma hemorrhaged rats. Coadministration of wortmannin or chromium-mesoporphyrin prevented the beneficial effects of resveratrol administration on postresuscitation proinflammatory responses and hepatic injury.


CONCLUSIONS
These findings collectively suggest that the salutary effects of resveratrol administration on attenuation of hepatic injury after trauma hemorrhage are likely mediated via up-regulation of Akt-dependent HO-1 expression.
Yu
Huang-Ping
HP
Department of Anesthesiology, Chang Gung University, Taoyuan, Taiwan.
Yang
Shun-Chin
SC
Lau
Ying-Tung
YT
Hwang
Tsong-Long
TL
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D054360:Chemokine CXCL1 / Q000032:analysis; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006470:Hemorrhage / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008099:Liver / Q000201:enzymology / Q000293:injuries*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D015854:Up-Regulation
D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D015850:Interleukin-6; D013267:Stilbenes; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol