Resveratrol attenuates intestinal injury after trauma hemmorhage. - GreenMedInfo Summary
Role of estrogen receptor-dependent upregulation of P38 MAPK/heme oxygenase 1 in resveratrol-mediated attenuation of intestinal injury after trauma-hemorrhage.
Shock. 2010 Dec 9. Epub 2010 Dec 9. PMID: 21192278
1Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan 2College of Medicine, Chang Gung University, Taoyuan, Taiwan 3Graduate Institute of Natural Products, Chang Gung University, Taoyuan, Taiwan 4Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, Taiwan 5Department of Cosmetic Science, Chang Gung Institute of Technology, Taoyuan, Taiwan.
Resveratrol protects against organ injury caused by trauma-hemorrhage, though the mechanism remains unknown. We previously have shown that it exerts protective effects in the liver via estrogen receptors and their signaling. Thus, we set out to determine whether or not resveratrol-mediated estrogen receptor-dependent p38 MAPK/hemeoxygenase-1 activation protects the intestine after trauma-hemorrhage. To study this, male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure∼40 mmHg for 90 min) followed by fluid resuscitation. Animals were pretreated with an estrogen receptor antagonist (ICI 182,780), a specific p38 MAPK inhibitor (SB-203580), or a hemeoxygenase enzyme antagonist (chromium-mesoporphyrin) 30 min before vehicle or resveratrol (30 mg/Kg) administration,followed by resuscitation, and were killed 2 h thereafter. Intestinal water content, myeloperoxidase (MPO) activity, and tumor necrosis factor (TNF)-α, interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, cytokine-induced neutrophil chemoattractant (CINC)-1, and CINC-3 levels, and edema of lung were measured. Mean arterial blood pressure, cardiac output, positive maximal pressure of left ventricular increase (+dP/dt), and negative maximal pressure of left ventricular decrease (-dP/dt) were also determined. Intestinal p38 MAPK activity and hemeoxygenase-1 expression were also determined. Trauma-hemorrhage led to an increase in intestinal water content, MPO activity, and TNF-α, IL-6, ICAM-1, CINC-1, and CINC-3 levels. This was accompanied by a decrease in intestinal p38 MAPK activity. Administration of resveratrol improved all of the above parameters. Resveratrol treatment alsoincreased intestinal hemeoxygenase-1 expression as compared to vehicle-treated trauma-hemorrhaged rats. Administration of ICI 182,780, SB-203850, or chromium-mesoporphyrin, with resveratrol abolished the resveratrol-mediated improvement of the above parameters. Resveratrol administration also attenuated trauma-hemorrhage-induced cardiac dysfunction and edema of lung. These results suggest that estrogen receptor-dependent up-regulation of the p38 MAPK/hemeoxygenase-1 pathway plays a critical role in mediating the salutary effects of resveratrol on shock-induced intestinal injury.