Mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, reduces trinitrobenzene sulfonic acid-induced colonic damage in rats.
The effect of mercaptoethylguanidine (MEG), a selective inhibitor of the inducible nitric oxide synthase and peroxynitrite scavenger, was evaluated in a rat model of colonic injury. A single intracolonic administration of trinitrobenzene sulfonic acid (TNBS, 20 mg/kg) dissolved in ethanol induced a severe colitis in male rats. Rats experienced bloody diarrhea and a significant loss of body weight. At 4 days after TNBS administration, the colon damage was characterized by areas of mucosal necrosis. Activity of myeloperoxidase, a marker of neutrophil infiltration, and levels of the 6-keto-prostaglandin F1alpha, were also markedly increased, whereas colonic ATP levels were reduced into the damaged tissue. Immunohistochemistry for the inducible nitric oxide synthase and nitrotyrosine, an index of nitrosative stress, showed an intense staining in the inflamed colon. Treatment with MEG (10 mg/kg i.v. b. i.d.) significantly reduced the appearance of diarrhea and the loss of body weight. This was associated with a remarkable amelioration of the disruption of the colonic architecture and suppression of the energetic failure, as well as a significant reduction of colonic myeloperoxidase activity and 6-keto-prostaglandin F1alpha levels. MEG also reduced the appearance of iNOS and nitrotyrosine immunoreactivity in the colon. The results of this study suggested that administration of MEG may be beneficial for the treatment of inflammatory bowel diseases.
Zingarelli
B
B
Children's Hospital Medical Center, Division of Critical Care, Cincinnati, Ohio, USA.
Cuzzocrea
S
S
Szabó
C
C
Salzman
A L
AL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009566:Nitrates / Q000032:analysis*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006146:Guanidines; D009566:Nitrates; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D014302:Trinitrobenzenesulfonic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C100078:2-mercaptoethylguanidine