Núcleo de Estudos E Pesquisas Tóxico-Farmacológicas, Faculdade de Farmácia, Universidade Federal de Goiás, Av. Universitária no. 1166 - Setor Leste Universitário, Goiânia, GO, 74605-010, Brazil.
Departamento de Biologia, Centro de Estudos E Pesquisas Biológicas, Pontifícia Universidade Católica de Goiás, Goiânia, GO, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Aug;394(8):1703-1711. doi: 10.1007/s00210-021-02103-4. Epub 2021 May 20.
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.
响尾蛇毒素是一种从响尾蛇毒液中分离出来的多肽毒素。虽然已经有几项研究确定了分离的响尾蛇毒素的许多生物学效应，但没有一项研究评估过其通过口服途径的急性毒性、镇痛和抗炎活性。本研究中的所有体内实验均在小鼠中进行。采用上下法和希波克拉底筛选法来评估可能的药理和毒性作用。采用醋酸诱导的腹部扭曲、甲醛诱导的疼痛测定、巴豆油诱导的耳肿胀和角叉菜胶诱导的胸膜炎来评估该毒素的镇痛和抗炎活性。响尾蛇毒素在测试的最大剂量（10.88mg/kg）下不会引起致死或中毒迹象。在 0.08、0.16 和 0.32mg/kg 的口服剂量下，扭体次数分别显著减少 34%、57%和 74%。在 0.16mg/kg 的剂量下，响尾蛇毒素可使神经源性相的疼痛反应时间减少 45%，使炎症相的疼痛反应时间减少 60%。此外，响尾蛇毒素通过减轻巴豆油诱导的耳肿胀的 77%来发挥抗水肿活性。在角叉菜胶诱导的胸膜炎中，白细胞、中性粒细胞和单核细胞向病变部位的迁移分别减少了 52%、46%和 59%。总之，响尾蛇毒素通过急性口服给药表现出体内镇痛和抗炎作用，在非毒性剂量下产生抗迁移作用机制。
