Resveratrol attenuates hepatic injury after trauma-hemorrhage via estrogen receptor-related pathway

Abstract

Resveratrol administration after adverse circulatory conditions is known to be protective, however, the mechanism by which resveratrol produces the salutary effects remains unknown. Recently, it was shown that resveratrol activates estrogen receptor (ER) in endothelial cells. We hypothesized that resveratrol administration in males after trauma-hemorrhage decreases cytokine production and protects against hepatic injury through an ER-dependent pathway. To study this, male Sprague-Dawley rats were subjected to trauma-hemorrhage (mean blood pressure, 40 mmHg for 90 min) then resuscitation. A single dose of resveratrol (30 mg/kg of body weight) with or without an ER antagonist (ICI 182,780), ICI 182,780, or vehicle was administered i.v. during resuscitation. Tissue myeloperoxidase activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant 1 (CINC-1), CINC-3, intercellular adhesion molecule 1, and interleukin 6 (IL-6) levels in the liver and plasma aspartate aminotransferase and alanine aminotransferase concentrations were measured at 2 and 24 h postresuscitation (n = 6 rats per group). One-way ANOVA and Tukey test were used for statistical analysis. Results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, CINC-1, CINC-3, intercellular adhesion molecule 1, and IL-6 levels and plasma aspartate aminotransferase and alanine aminotransferase concentrations. These parameters were significantly improved in the resveratrol-treated rats at both 2 and 24 h postresuscitation. Coadministration of the ER antagonist ICI 182,780 prevented the beneficial effects of resveratrol administration on postresuscitation proinflammatory responses and hepatic injury. Thus, resveratrol administration after trauma-hemorrhage attenuated hepatic injury, likely through reduction of proinflammatory mediators. Resveratrol-mediated hepatic preservation seemed to progress via an ER-related pathway.