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. Conclusion: 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.