Role of Akt-dependent up-regulation of hemeoxygenase-1 in resveratrol-mediated attenuation of hepatic injury after trauma hemorrhage.

Abstract

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.

• Authors: Huang-Ping Yu, Shun-Chin Yang, Ying-Tung Lau, Tsong-Long Hwang
• Journal: Surgery (Surgery) Vol. 148 Issue 1 Pg. 103-9 (Jul 2010) ISSN: 1532-7361 [Electronic] United States
• PMID: 20117814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Mosby, Inc. All rights reserved.

Chemical References

• Chemokine CXCL1
• Cxcl1 protein, rat
• Interleukin-6
• Stilbenes
• Intercellular Adhesion Molecule-1
• Peroxidase
• Heme Oxygenase-1
• Aspartate Aminotransferases
• Alanine Transaminase
• Proto-Oncogene Proteins c-akt
• Resveratrol

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Chemokine CXCL1 (analysis)
• Heme Oxygenase-1 (physiology)
• Hemorrhage (drug therapy)
• Intercellular Adhesion Molecule-1 (analysis)
• Interleukin-6 (analysis)
• Liver (enzymology, injuries)
• Male
• Peroxidase (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (physiology)
• Rats
• Rats, Sprague-Dawley
• Resveratrol
• Stilbenes (therapeutic use)
• Up-Regulation