title: Effect of methylguanidine in carrageenan-induced acute inflammation in the rats.
abstract: In vitro and in vivo studies have demonstrated that methylguanidine, an inhibitor of nitric oxide synthase (NOS), is also able to reduce tumour necrosis factor-alpha (TNF-alpha) release. In the present study, we evaluated the anti-inflammatory potential of methylguanidine treatment in two models of acute inflammation (carrageenan-induced paw edema and pleurisy) where oxyradical, nitric oxide (NO) and prostaglandins play a crucial role in the inflammatory processes. Our data show that methylguanidine, given intraperitoneally at the dose of 30 mg/kg, inhibits the inflammatory response reducing significantly (P<0.05) paw swelling, pleural exudates formation, mononuclear cell infiltration and histological injury. Furthermore, our data suggests that there is a significant (P<0.05) reduction in the activity and expression both of the inducible NOS (iNOS) and of cyclooxygenase-2 in lung tissue of pleurisy model. Methylguanidine is also able to reduce the appearance of nitrotyrosine and of the nuclear enzyme poly(adenosine diphosphate [ADP]-ribose) synthase immunoreactivity in the inflamed lung tissues. Treatment with aminoguanidine, the reference drug, significantly reduced all the evaluated pro-inflammatory parameters in carrageenan-treated rats. Taken together, the present results demonstrate that methylguanidine exerts potent anti-inflammatory effects that could be, in part, related to an inhibition of the expression/activity of the iNOS and cyclooxygenase-2 and, another part, may be related to a reduction of TNF-alpha release.
authors.affiliation: Department of Pharmaceutical Sciences University of Salerno, Via Ponte Don Melillo 11/c, 84084 Fisciano-Salerno, Italy. smarzocco@unisa.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzocco
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Ivana
authors.initials: I
authors.lastname: Serraino
authors.forename: Raffaella
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meli
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Mattaceraso
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Autore
mesh_terms: D000208:Acute Disease; D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008760:Methylguanidine / Q000494:pharmacology / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010998:Pleurisy / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009569:Nitric Oxide; D008760:Methylguanidine; D002351:Carrageenan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat