Role of endothelins in trinitrobenzene sulfonic acid-induced colitis in rats.

To determine the role of endothelins (ET) on experimental colitis, following intracolonic trinitrobenzene sulfonic acid administration, rats were given orally either bosentan (BS), a nonselective ET receptor antagonist (100 mg/kg in 5% arabic gum), or arabic gum by gavage for 2 or 14 days. Macroscopic damage scores obtained in the vehicle (1.4+/-0.4), acute (4.8+/-0.6) and chronic (3.8+/-0.3) colitis groups were significantly higher than in the control group (0). BS treatment reduced the scores in both acute (3+/- 0.5) and chronic (2.3+/-0.5) colitis groups. Myeloperoxidase (MPO) activities of colonic tissues were elevated in acute and chronic colitis groups (325.1+/-44.9 and 431.8+/-54.6 U/g wet weight) as compared with the control group (73.6+/-11 U/g wet weight). Plasma protein oxidation levels were found to be significantly increased in the chronic colitis group (1,158.1+/-63.4 nmol/ml) compared with the control, ethanol and acute colitis groups (274.3+/-23.1, 490+/-52.2 and 422.2+/-50.5 nmol/ml). BS treatment significantly reduced both the protein oxidation level (375.5+/-46.9 nmol/ml) and MPO activity (167.5+/-35.8 U/g wet weight). The results of the present study suggest the involvement of ETs in the pathogenesis of colonic injury in this animal model of colitis.