title: Inflammatory effects of patagonfibrase, a metalloproteinase from Philodryas patagoniensis (Patagonia Green Racer; Dipsadidae) venom.
abstract: Patagonfibrase is a P-III class metalloproteinase isolated from the venom of Philodryas patagoniensis, a South-American, rear-fanged 'colubrid' snake responsible for accidents with clinical significance. Since local inflammatory reactions are conspicuous signs of snakebites inflicted by this species and taking into consideration that most snake venom metalloproteinases exhibit inflammatory activity, this study deals with the proinflammatory effects evoked by patagonfibrase. Herein, we demonstrate that patagonfibrase causes a time- and dose-dependent hemorrhagic edema when injected into mouse hind paws. The peak of edema occurred at 30 min after injection, and the minimum edematogenic dose was 0.021 μg. By histological analysis, the presence of moderate to marked edema and hemorrhage, and a mild inflammatory infiltrate was observed. When injected subcutaneously into the scrotal bag of mice, patagonfibrase induced cell recruitment with a significant alteration in physiological parameters of leukocyte-endothelium interaction. The presence of 1 mmol/L o-phenanthroline, which chelates metal ions, significantly inhibited the proinflammatory effects induced by patagonfibrase. Taken together, these results imply that patagonfibrase is an important contributor to local inflammation elicited by P. patagoniensis envenomation, which may pave the way for novel therapeutic strategies to treat this snakebite. Moreover, our findings demonstrate for the first time that a venom metalloproteinase from a rear-fanged snake elicits proinflammatory effects mainly mediated by its catalytic activity.
authors: Cátedra de Farmacología, Facultad de Ciencias Veterinarias, Universidad Nacional del Nordeste, Sargento Cabral 2139, 3400 Corrientes, Argentina. mepeichoto@yahoo.com.ar
authors: María Elisa
authors: ME
authors: Peichoto
authors: Bianca Cestari
authors: BC
authors: Zychar
authors: Flávio Luiz
authors: FL
authors: Tavares
authors: Luis Roberto
authors: LR
authors: de Camargo Gonçalves
authors: Ofelia
authors: O
authors: Acosta
authors: Marcelo Larami
authors: ML
authors: Santoro
mesh_terms: D000818:Animals; D017812:Colubridae; D004487:Edema / Q000139:chemically induced; D006470:Hemorrhage / Q000139:chemically induced; D007249:Inflammation / Q000139:chemically induced*; D007279:Injections, Subcutaneous; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D045726:Metalloproteases / Q000494:pharmacology*; D051379:Mice; D012910:Snake Venoms / Q000494:pharmacology*
chemical_list: D012910:Snake Venoms; D045726:Metalloproteases; C519455:patagonfibrase, Philodryas patagoniensis