Effect of methylguanidine in carrageenan-induced acute inflammation in the rats.
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.
Marzocco
Stefania
S
Department of Pharmaceutical Sciences University of Salerno, Via Ponte Don Melillo 11/c, 84084 Fisciano-Salerno, Italy. smarzocco@unisa.it
Di Paola
Rosanna
R
Serraino
Ivana
I
Sorrentino
Raffaella
R
Meli
Rosaria
R
Mattaceraso
Giuseppina
G
Cuzzocrea
Salvatore
S
Pinto
Aldo
A
Autore
Giuseppina
G
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
D009569:Nitric Oxide; D008760:Methylguanidine; D002351:Carrageenan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat