Methylguanidine reduces the development of non septic shock induced by zymosan in mice.
In the present study we evaluate the effect of methylguanidine (MG), a product of protein catabolism, in a model of acute inflammation (zymosan induced inflammation) in mice where oxyradical and nitric oxide (NO) play a crucial role. Our data show that MG, given intraperitoneally at the dose of 30 mg/Kg, inhibits the inflammatory response reducing significantly (P < 0.05) peritoneal exudates formation, mononuclear cell infiltration and histological injury in mice. Furthermore, our data suggests that there is a significant (P < 0.05) reduction in kidney, liver and pancreas injury as demonstrated by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubine and alkaline phosfatase levels. MG is also able to reduce the appearance of nitrotyrosine and of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) synthase (PARS) immunoreactivity in the inflamed intestinal and lung tissues. The histological examination revealed a significant reduction in zymosan-induced intestinal and lung damage in MG-treated mice. Taken together, the present results demonstrate that MG exerts potent anti-inflammatory effects on zymosan-induced shock.
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
Genovese
Tiziana
T
Sorrentino
Raffaella
R
Britti
Domenico
D
Scollo
Giuseppe
G
Pinto
Aldo
A
Cuzzocrea
Salvatore
S
Autore
Giuseppina
G
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005122:Exudates and Transudates / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008760:Methylguanidine / Q000627:therapeutic use*; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010538:Peritonitis / Q000188:drug therapy*; D009195:Peroxidase / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000276:immunology / Q000378:metabolism; D012769:Shock / Q000139:chemically induced* / Q000188:drug therapy*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015054:Zymosan / Q000633:toxicity*
D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D008760:Methylguanidine; D015054:Zymosan; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases