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Jaqueline de Cássia Proença-Assunção,1 Anna Paula Farias-de-França,2 Natalia Tribuiani,1 Jose Carlos Cogo,3 Rita de Cássia Collaço,4 Priscila Randazzo-Moura,5 Sílvio Roberto Consonni,6 Marco Vinicius Chaud,1 Carolina Alves dos Santos,2 Yoko Oshima-Franco1 1Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (Uniso), Sorocaba, SP, Brazil; 2Pharmacy Graduate Course, University of Sorocaba (Uniso), Sorocaba, SP, Brazil; 3Bioengineering and Biomedical Engineering Programs, Technological and Scientific Institute, Brazil University, São Paulo, Brazil; 4Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil; 5Department of Surgery, Pontifícia Universidade Católica De São Paulo (PUCSP), Sorocaba, SP, Brazil; 6Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, BrazilCorrespondence: Yoko Oshima-FrancoUniversity of Sorocaba (UNISO), Rodovia Raposo Tavares, Km 92.5, Sorocaba, 18023-000, SP, BrazilTel +55 15 2101-7197Fax +55 15-2101-7112Email yoko.franco@prof.uniso.brPurpose: A silver nanoparticle obtained by reducing salts with solid dispersion of curcumin (130 nm, 0.081 mg mL− 1) was used to counteract against the toxic – edematogenic, myotoxic, and neurotoxic – effects of Philodryas olfersii venom.Methods: The edematogenic effect was evaluated by plasma extravasation in rat dorsal skin after injection of 50 μg per site of venom alone or preincubated with 1, 10, and 100 μL of AgNPs; the myotoxicity was evaluated by measuring the creatine kinase released into the organ-bath before the treatment and at the end of each experiment; and neurotoxicity was evaluated in chick biventer cervicis using the conventional myographic technique, face to the exogenous acetylcholine (ACh) and potassium chloride (KCl) added into the bath before the treatment and after each experiment. Preliminarily, a concentration-response curve of AgNPs was carried out to select the concentration to be used for neutralizing assays, which consists of neutralizing the venom-induced neuromuscular paralysis and edema by preincubating AgNPs with venom for 30 min.Results: The P. olfersii venom-induced edema (n=6) and a complete neuromuscular blockade (n=4) that includes the total and unrecovered block of ACh and KCl contractures. AgNPs produced a concentration-dependent decrease the venom-induced edema (n=6) from 223.3% to 134.4% and to 100.5% after 10 and 100 μL AgNPs-preincubation, respectively. The preincubation of venom with AgNPs (1 μL; n=6) was able to maintain 46.5 ± 10.9% of neuromuscular response under indirect stimuli, 39.2 ± 9.7% of extrinsic nicotinic receptors functioning in absence of electrical stimulus and 28.3 ± 8.1% of responsiveness to potassium on the sarcolemmal membrane. The CK release was not affected by any experimental protocol which was like control.Conclusion: AgNPs interact with constituents of P. olfersii venom responsible for the edema-forming activity and neuromuscular blockade, but not on the sarcolemma membrane-acting constituents. The protective effect of the studied AgNPs on avian preparation points out to molecular targets as intrinsic and extrinsic nicotinic receptors.Keywords: chick biventer cervicis, opisthoglyphous snakes, Philodryas olfersii, neuromuscular blockade, silver nanoparticles |
