Inflammatory effects of patagonfibrase, a metalloproteinase from Philodryas patagoniensis (Patagonia Green Racer; Dipsadidae) venom

Autor(es)

Elisa Peichoto, Maria ^{[1, 2]} ; Zychar, Bianca Cestari ^[1] ; Luiz Tavares, Flavio ^{[1, 3]} ; Goncalves, Luis Roberto Camargo ^[1] ; Acosta, Ofelia ^[2] ; Santoro, Marcelo Larami ^[1]

Afiliação do(s) autor(es)

^[1] Inst Butantan, Lab Fisiopatol, BR-05503900 Sao Paulo - Brazil

^[2] Univ Nacl Nordeste, Fac Ciencias Vet, Catedra Farmacol, RA-3400 Corrientes - Argentina

^[3] Univ Cuenca Plata, Fac Ingn, Catedra Fisiol, RA-3400 Corrientes - Argentina

• Tipo de documento: Artigo Científico
• Fonte: Experimental Biology and Medicine; v. 236, n. 10, p. 1166-1172, OCT 2011.
• Citações Web of Science: 10

Resumo

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 mu g. 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. (AU)

• Processo FAPESP: 08/02996-8 - Venenos de serpentes Bothrops jararaca recém-nascidas e adultas: comparação entre suas atividades enzimáticas e biológicas, imunoneutralização, composição química e capacidade de induzir alterações hemostáticas
• Beneficiário: Marcelo Larami Santoro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/52559-3 - Importância da lesão local induzida por metaloproteinases de venenos ofídicos na indução de plaquetopenia em envenenamentos
• Beneficiário: Marcelo Larami Santoro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/08162-1 - Contribuição das lesões locais induzidas pelo veneno da serpente Bothrops jararaca para a gênese de distúrbios hemostáticos sistêmicos
• Beneficiário: Marcelo Larami Santoro
• Modalidade de apoio: Auxílio à Pesquisa - Regular