Estrogen alleviates acetic acid-induced gastric or colonic damage via both ERα- and ERβ-mediated and direct antioxidant mechanisms in rats.

In order to demonstrate the possible protective effects of estrogen receptor (ER)-α and ERβ receptor subtypes in the pathogenesis of colonic and gastric oxidant damage, experimental ulcer and colitis were induced by acetic acid, and the animals were randomly divided as colitis, ulcer, and their corresponding non-ulcer and non-colitis control groups. Each group of rats was treated intramuscularly with the vehicle, selective ERα agonist propylpyrazole-triol (1 mg/kg), ERβ agonist diarylpropionitrile (1 mg/kg), non-selective ER agonist 17β estradiol (E2; 1 mg/kg), or E2 plus non-selective ER antagonist ICI-182780 (1 mg/kg). The results revealed that induction of ulcer or colitis resulted in systemic inflammation as assessed by increased levels of plasma TNF-α and IL-6 levels. In both tissues, the presence of oxidant damage was verified by histological analysis and elevated myleoperoxidase activity. In the colitis and ulcer groups, both ER agonists and the non-selective E2 reversed the oxidative damage in a similar manner. These findings indicate that estrogen acts via both ERα- and ERβ-mediated and direct antioxidant mechanisms, where both ER subtypes play equal and efficient roles in the anti-inflammatory action of estrogen, in limiting the migration of neutrophils to the inflamed tissue, reducing the release and activation of cytokines and thereby alleviating tissue damage.