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.
Güllüoglu
B M
BM
Department of General Surgery, Marmara University School of Medicine, Istanbul, Turkey.
Kurtel
H
H
Güllüoglu
M G
MG
Yegen
C
C
Aktan
A O
AO
Dizdaroglu
F
F
Yalin
R
R
Yegen
B C
BC
D000704:Analysis of Variance; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D000077300:Bosentan; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D000431:Ethanol; D005772:Gastrointestinal Transit; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid
D001798:Blood Proteins; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000431:Ethanol; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D000077300:Bosentan