Effects of N-acetylcysteine plus mesalamine on prostaglandin synthesis and nitric oxide generation in TNBS-induced colitis in rats.
The aim of the present studies was to examine mechanisms by which the rectally administered combination of N-acetylcysteine (NAC) plus mesalamine (5-ASA) affects inducers of inflammation to promote mucosal healing and reduce tissue inflammation in chemically (trinitrobenzene sulfonic acid, TNBS) induced colitis in rats. Experimental findings demonstrate that dual therapy with NAC plus 5-ASA was superior to individual agents in reducing histological measures of colitis. NAC alone and in combination with 5-ASA suppressed COX2 gene expression and prostaglandin E(2) (PGE(2)) levels to control values. Furthermore, NAC plus 5-ASA reduced nitrate generation, an expression of inducible nitric oxide synthase (iNOS) activity, to basal levels and these results were significantly lower than those observed with either NAC or 5-ASA alone. In conclusion, these results indicate that NAC plus 5-ASA exerts therapeutic benefit, in part by countering the actions of PGE(2) and the deleterious effects of oxidative and nitrosative stress induced by TNBS colitis.
Ancha
Hanumantha R
HR
Division of Gastroenterology, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Kurella
Ravi R
RR
McKimmey
Christine C
CC
Lightfoot
Stanley
S
Harty
Richard F
RF
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000201:enzymology / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D019804:Mesalamine / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D008565:Membrane Proteins; D009569:Nitric Oxide; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; D000111:Acetylcysteine