Abstract
Crotamine is a polypeptide toxin isolated from rattlesnake venom. Although several studies have been developed identifying many biological effects of isolated crotamine, none of them evaluated its acute toxicity, antinociceptive, and anti-inflammatory activities through oral administration. All in vivo experiments from this study were performed in mice. The up-and-down procedure and hippocratic screening were carried out to evaluate possible pharmacological and toxic effects. Antinociceptive and anti-inflammatory activities of this toxin were evaluated using acetic acid-induced abdominal writhing, formalin-induced pain assays, croton oil-induced ear edema, and carrageenan-induced pleurisy. Crotamine did not cause lethality or signs of intoxication up to the maximum dose tested (10.88 mg/kg). The number of contortions was reduced significantly by 34, 57, and 74% at the oral doses of 0.08, 0.16, and 0.32 mg/kg, respectively. At the dose of 0.16 mg/kg, crotamine decreases pain time-reactivity at neurogenic phase by 45% and at inflammatory phase by 60%. Also, crotamine elicited antiedematogenic activity through the attenuation of the croton oil-induced ear edema by 77%. In the carrageenan-induced pleurisy, the leukocyte, neutrophil, and mononuclear cell migration to the lesion site were reduced by 52%, 46%, and 59%, respectively. Altogether, crotamine demonstrated in vivo antinociceptive and anti-inflammatory effect through acute oral administration, generating an anti-migratory mechanism of action at non-toxic doses.
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Acknowledgements
The authors thank to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG) for a scholarship support to M.sc. Moreira, LA.
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LCC and LAM conceived and designed this research. MRM and SAMO collected, extracted, and purified the biological material. LAM, JRON, and LPO conducted experiments and analyzed data. LAM, JOF, and ACC wrote and revised the manuscript. PMGC and AAVC revised the manuscript and gave critical and scientific considerations. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Highlights
• Oral isolated crotamine administration demonstrated low toxicity at dose ranging 0.34–10.88 mg/kg, without sings of intoxication or lethality.
• A relevant antinociceptive effect was achieved after acute low oral dose of crotamine, decreasing significantly abdominal writhing number and pain-time reactivity.
• Crotamine was able to reduce significantly ear edema and leukocyte migration, demonstrating an interesting anti-inflammatory activity.
• These promising results contribute to understand the behavior of crotamine in vivo on the pain and inflammation handling.
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Moreira, L.A., Oliveira, L.P., Magalhães, M.R. et al. Acute toxicity, antinociceptive, and anti-inflammatory activities of the orally administered crotamine in mice. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1703–1711 (2021). https://doi.org/10.1007/s00210-021-02103-4
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DOI: https://doi.org/10.1007/s00210-021-02103-4