Role of Estrogen Receptor in Astringinin-Mediated Attenuation of intestinal Injury after Trauma-Hemorrhage

Astringinin protects against organ injury caused by trauma-hemorrhage though the mechanism remains unknown. We hypothesize that astringinin administration in males following trauma-hemorrhage protects against intestinal injury through an estrogen receptor-dependent pathway. To test this hypothesis, male Sprague-Dawley rats were subject to 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) 30 min before vehicle or astringinin (0.3 mg/kg) administration, followed by resuscitation, and the treated rats were killed 24 h thereafter. Intestinal wet/dry weight ratio, myeloperoxidase (MPO) activity, and the levels of interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-3 were measured. Traumahemorrhage led to an increase in intestinal wet/dry weight ratio, MPO activity, histological damage and also increases in the levels of IL-6, ICAM-1, CINC-1 and CINC-3. Administration of astringinin improved all of the above parameters. Administration of ICI 182,780 with astringinin abolished the astringinin-mediated improvement of the above parameters. These results suggest that the estrogen receptor-dependent pathway likely plays a critical role in mediating the salutary effects of astringinin on shock-induced intestinal injury.