title: L-arginine and aminoguanidine reduce colonic damage of acetic acid-induced colitis in rats: potential modulation of nuclear factor-κB/p65.
abstract: The transcription factor, nuclear factor-κB (NF-κB) is a key inducer of inducible nitric oxide synthase (iNOS) gene expression. The aim of the present study was to investigate the potential protective effect of l-arginine (Arg; nitric oxide precursor) and aminoguanidine (inducible nitric oxide synthase inhibitor) against acetic acid (AA)-induced colitis in rats, and the potential role of NF-κB. Colitis was induced by intrarectal inoculation of rats with 4% acetic acid for three consecutive days. The effect of Arg and aminoguanidine on nitric oxide levels was assessed by Greiss assay and protein expression of NF-κB/p65, and inducible nitric oxide synthase was also investigated by immunohistochemistry. Slides were examined using ImageJ, and results reported as the percent area positive for each marker. Intrarectal AA caused a significant increase in bodyweight loss and colon weights. Arg at 100 mg/day for 7 days before induction of colitis diminished the changes in both bodyweight loss and colon weights. Furthermore, Arg attenuated the colonic tissues macroscopic and microscopic damage induced by acetic acid. In addition, i.p. AG 100 mg/kg given during and after induction of colitis recovered the colonic ulcerative lesion induced by AA. Arg can protect against colonic inflammation; an effect that probably be attributed to its nitric oxide-donating property, resulting in modulatory effects on the expression of NF-κB/p65 in the colon tissues. The results suggested that Arg might reduce the inflammation associated with colitis as confirmed by histopathological investigations. Arg might inhibit AA-induced colitis through the NF-κB/nitric oxide pathway.
authors.affiliation: Pharmacology Department, Faculty of Medicine, Assiut University, Assiut, Egypt; Therapeutic Drug Monitoring Laboratory, Assiut University Hospitals, Assiut, Egypt.
authors.forename: Hanan S M
authors.initials: HS
authors.lastname: Farghaly
authors.forename: Romany H
authors.initials: RH
authors.lastname: Thabit
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006146:Guanidines; D016328:NF-kappa B; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D019342:Acetic Acid; C004479:pimagedine
keywords: acetic acid; aminoguanidine; colitis; l-arginine; nuclear factor-κB; rats