Autor: |
Teixeira-Cruz JM; Graduate Program in Pharmacology and Medicinal Chemistry, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil., Strauch MA; Graduate Program in Pharmacology and Medicinal Chemistry, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.; Scientific Board, Vital Brazil Institute (IVB), Niterói, Rio de Janeiro 24230-410, Brazil., Monteiro-Machado M; Graduate Program in Pharmacology and Medicinal Chemistry, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil., Tavares-Henriques MS; Graduate Program in Pharmacology and Medicinal Chemistry, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil., de Moraes JA; Graduate Program in Pharmacology and Medicinal Chemistry, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil., Ribeiro da Cunha LE; Scientific Board, Vital Brazil Institute (IVB), Niterói, Rio de Janeiro 24230-410, Brazil., Ferreira RS Jr; Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP), Botucatu, São Paulo 18610-307, Brazil., Barraviera B; Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP), Botucatu, São Paulo 18610-307, Brazil., Quintas LEM; Graduate Program in Pharmacology and Medicinal Chemistry, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil., Melo PA; Graduate Program in Pharmacology and Medicinal Chemistry, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. |
Abstrakt: |
Massive, Africanized honeybee attacks have increased in Brazil over the years. Humans and animals present local and systemic effects after envenomation, and there is no specific treatment for this potentially lethal event. This study evaluated the ability of a new Apilic antivenom, which is composed of F(ab')2 fraction of specific immunoglobulins in heterologous and hyperimmune equine serum, to neutralize A. mellifera venom and melittin, in vitro and in vivo, in mice. Animal experiments were performed in according with local ethics committee license (UFRJ protocol no. DFBCICB072-04/16). Venom dose-dependent lethality was diminished with 0.25-0.5 μL of intravenous Apilic antivenom/μg honeybee venom. In vivo injection of 0.1-1 μg/g bee venom induced myotoxicity, hemoconcentration, paw edema, and increase of vascular permeability which were antagonized by Apilic antivenom. Cytotoxicity, assessed in renal LLC-PK1 cells and challenged with 10 μg/mL honeybee venom or melittin, was neutralized by preincubation with Apilic antivenom, as well the hemolytic activity. Apilic antivenom inhibited phospholipase and hyaluronidase enzymatic activities. In flow cytometry experiments, Apilic antivenom neutralized reduction of cell viability due to necrosis by honeybee venom or melittin. These results showed that this antivenom is effective inhibitor of honeybee venom actions. Thus, this next generation of Apilic antivenom emerges as a new promising immunobiological product for the treatment of massive, Africanized honeybee attacks. |