Η μελέτη της αντιοξειδωτικής και αντιφλεγμονώδους δράσης μορίων (U-74389G και σιλδεναφίλης) σε πειραματικό πρότυπο χημικής αιμορραγικής κολίτιδας σε επίμυες: βιοχημική μελέτη

Abstract

BACKGROUND: Crohn disease is still incurable. Compounds with anti-inflammatory and/or antioxidativeeffects are tested in various preclinical models of the disease. Our aim was to investigate theeffects of sildenafil and lazaroid U-74389G in an experimental rat model oftrinitrobenzenesulfonic acid-induced colitis.MATERIALS AND METHODS:Trinitrobenzenesulfonic acid was instilled into the colon of all male Wistar rats except for therats belonging to the first group. For 6 days, the animals in group 3 were administered dailysildenafil orally, the rats in group 4 were administered daily U-74389G intravenously, and therats in group 5 were coadministered daily sildenafil orally and intravenous U-74389G. Therats in groups 1 and 2 were not administered any treatment. During the study, the weightswere recorded as a marker of clinical condition. The colon damage was evaluated usingmacroscopic colon mucosal damage index (CMDI), microscopic (Geboes score), andbiochemical methods (tissue tumor necrosis factor [TNF]-αΝandΝmalondialdehydeΝ[εϊχ]ΨέRESULTS:Sildenafil reduced TNF-αΝtissueΝlevelsΝandΝincreasedΝbodyΝweightέΝU-74389G reduced TNF-α,Νthe macroscopic index of mucosal damage score (CMDI) and increased body weight. Thecombined treatment with sildenafil and U-74389G reduced tissue levels of both TNF-αΝandΝMDA, lowered CMDI and microscopic Geboes score, and increased body weight. CONCLUSIONS:U-74389G demonstrated a significant anti-inflammatory activity related to its ability to reducecolonic TNF-α,ΝωεϊIΝscore, and improve weight change. We confirmed that sildenafil hasanti-inflammatory capacity by reducing colonic TNF-αΝandΝbyΝimprovingΝbodyΝweightέΝόinally,Νthe combined treatment showed superior effects by reducing colonic TNF-α,ΝcolonicΝεϊχ,ΝCMDI score, Geboes score, and by improving weight.