title: Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase, a metalloproteinase isolated from Bothrops atrox snake venom.
abstract: Snake venom metalloproteinases have been described as responsible for several inflammatory effects. In this study, we investigated the edema and hyperalgesia induced in rats by Batroxase, a P-I metalloproteinase from Bothrops atrox venom, along with possible inflammatory mediators involved in these responses. Batroxase or sterile saline was injected into rat paws and the edema and hyperalgesic effects were evaluated for 6h by using a plethysmometer and a Von Frey system, respectively. Batroxase induced significant edematogenic and hyperalgesic peak responses in the first hours after administration. The inflammatory mediators involved in these responses were assayed by pretreatment of animals with synthesis inhibitors or receptor antagonists. Peak responses were significantly reduced by administration of the glucocorticoid dexamethasone, the H1 receptor antagonist diphenhydramine and the FLAP inhibitor MK-886. Rat paws injected with compound 48/80, a mast cell degranulating agent, followed by Batroxase injection resulted in significant reduction of the edema and hyperalgesia. However, Batroxase itself induced minor degranulation of RBL-2H3 mast cells in vitro. Additionally, the inflammatory responses did not seem to be related to prostaglandins, bradykinin or nitric oxide. Our results indicate a major involvement of histamine and leukotrienes in the edema and hyperalgesia induced by Batroxase, which could be related, at least in part, to mast cell degranulation.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto-SP, Brazil.
authors.forename: Lanuze G B
authors.initials: LG
authors.lastname: De Toni
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto-SP, Brazil.
authors.forename: Danilo L
authors.initials: DL
authors.lastname: Menaldo
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto-SP, Brazil.
authors.forename: Adélia C O
authors.initials: AC
authors.lastname: Cintra
authors.affiliation: Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto-SP, Brazil.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Figueiredo
authors.affiliation: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
authors.forename: Anderson R
authors.initials: AR
authors.lastname: de Souza
authors.affiliation: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
authors.forename: William M A
authors.initials: WM
authors.lastname: Maximiano
authors.affiliation: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Jamur
authors.affiliation: Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto-SP, Brazil.
authors.forename: Glória E P
authors.initials: GE
authors.lastname: Souza
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto-SP, Brazil. Electronic address: suvilela@usp.br.
authors.forename: Suely V
authors.initials: SV
authors.lastname: Sampaio
mesh_terms: D000818:Animals; D017837:Bothrops; D015550:Cell Degranulation / Q000187:drug effects; D003435:Crotalid Venoms / Q000201:enzymology*; D004487:Edema / Q000139:chemically induced / Q000473:pathology*; D005528:Foot / Q000473:pathology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D045726:Metalloproteases; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: C000608699:Batroxase, Bothrops atrox; D003435:Crotalid Venoms; D018836:Inflammation Mediators; D045726:Metalloproteases
keywords: Batroxase; Edema; Hyperalgesia; Inflammatory mediators; Metalloproteinases; Snake venoms