A Novel Apilic Antivenom to Treat Massive, Africanized Honeybee Attacks: A Preclinical Study from the Lethality to Some Biochemical and Pharmacological Activities Neutralization

Jhonatha da Mota Teixeira-Cruz; Marcelo Abrahão Strauch; Marcos Monteiro-Machado; Matheus da Silva Tavares-Henriques; João Alfredo de Moraes; Luís Eduardo Ribeiro da Cunha; Rui Seabra Ferreira; Benedito Barraviera; Luis Eduardo M. Quintas; Paulo A. Melo

A Novel Apilic Antivenom to Treat Massive, Africanized Honeybee Attacks: A Preclinical Study from the Lethality to Some Biochemical and Pharmacological Activities Neutralization

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 ApilicApilic antivenom, which is composed of F(ab&rsquo:)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&ndash:0.5 &mu:L of intravenous ApilicApilic antivenom/&mu:g honeybee venom. In vivo injection of 0.1&ndash:1 &mu:g/g bee venom induced myotoxicity, hemoconcentration, paw edema, and increase of vascular permeability which were antagonized by ApilicApilic antivenom. Cytotoxicity, assessed in renal LLC-PK1 cells and challenged with 10 &mu:g/mL honeybee venom or melittin, was neutralized by preincubation with ApilicApilic antivenom, as well the hemolytic activity. Apilic antivenom inhibited phospholipase and hyaluronidase enzymatic activities. In flow cytometry experiments, ApilicApilic 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 ApilicApilic antivenom emerges as a new promising immunobiological product for the treatment of massive, Africanized honeybee attacks.

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