title: Local and hematological alterations induced by Philodryas olfersii snake venom in mice.
abstract: Envenomation by the South American opisthoglyphous snake Philodryas olfersii causes local pain, edema, erythema and ecchymosis; systemic envenomation is rare. In this work, we examined the inflammatory activity of P. olfersii venom (10, 30 and 60 μg) in mouse gastrocnemius muscle 6 h after venom injection. Intramuscular injection of venom did not affect hematological parameters such as red cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. The venom caused thrombocytopenia (at all three doses), leukopenia and lymphopenia (both at the two highest doses), as well as neutrophilia (30 μg), monocytosis (30 μg) and basophilia (10 μg). Of the cytokines that were screened [IL-1β, IL-6, IL-10, IL-13, IL-17, TNF-α, IFN-γ, MIP-2 and KC] and IGF-1, only IGF-1 showed a significant increase in its circulating concentration, seen with 60 μg of venom; there were no significant changes in the cytokines compared to control mice. Histological analysis revealed the presence of edema, an inflammatory infiltrate and progressive myonecrosis. Edema and myonecrosis were greatest with 60 μg of venom, while the inflammatory infiltrate was greatest with 10 μg of venom. All venom doses caused the migration of polymorphonuclear and mononuclear leukocytes into muscle, but with no significant dose-dependence in the response. These findings show that, at the doses tested, P. olfersii venom does not cause hematological alterations and has limited effect on circulating cytokine concentrations. These data also confirm that the principal effects of the venom in mice are local edema, inflammatory cell infiltration and myonecrosis.
authors.affiliation: Laboratory of Histology and Regenerative Therapy, Institute of Research and Development (IP&D), Vale do Paraíba University (UNIVAP), Avenida Shishima Hifumi, 2911, Urbanova, 12244-000, São José dos Campos, SP, Brazil.
authors.forename: Juliana S
authors.initials: JS
authors.lastname: Oliveira
authors.affiliation: Laboratory of Histology and Regenerative Therapy, Institute of Research and Development (IP&D), Vale do Paraíba University (UNIVAP), Avenida Shishima Hifumi, 2911, Urbanova, 12244-000, São José dos Campos, SP, Brazil. Electronic address: lucianabsa@gmail.com.
authors.forename: Luciana B
authors.initials: LB
authors.lastname: Sant'Anna
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), 01504-000, São Paulo, SP, Brazil.
authors.forename: Manoel C
authors.initials: MC
authors.lastname: Oliveira Junior
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), 01504-000, São Paulo, SP, Brazil.
authors.forename: Pamella R M
authors.initials: PRM
authors.lastname: Souza
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), 01504-000, São Paulo, SP, Brazil.
authors.forename: Adilson S
authors.initials: AS
authors.lastname: Andrade Souza
authors.affiliation: Laboratory of Pharmacology and Biochemistry, Institute of Research and Development (IP&D), Vale do Paraíba University (UNIVAP), Avenida Shishima Hifumi, 2911, Urbanova, 12244-000, São Jose dos Campos, SP, Brazil.
authors.forename: Wellington
authors.initials: W
authors.lastname: Ribeiro
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), 01504-000, São Paulo, SP, Brazil; Department of Bioengineering and Biomedical Engineering, Brazil University, Rua Carolina Fonseca, 584/235 (Campus I and II), Vila Santana, 08230-030, Itaquera, São Paulo, SP, Brazil.
authors.forename: Rodolfo P
authors.initials: RP
authors.lastname: Vieira
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hyslop
authors.affiliation: Department of Bioengineering and Biomedical Engineering, Brazil University, Rua Carolina Fonseca, 584/235 (Campus I and II), Vila Santana, 08230-030, Itaquera, São Paulo, SP, Brazil.
authors.forename: José C
authors.initials: JC
authors.lastname: Cogo
mesh_terms: D000818:Animals; D017812:Colubridae; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D012910:Snake Venoms / Q000633:toxicity*
chemical_list: D016207:Cytokines; D012910:Snake Venoms; D007334:Insulin-Like Growth Factor I
keywords: Acute inflammation; Cytokines; Edema; Inflammatory infiltrate; Myonecrosis; Philodryas olfersii venom