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巴塔戈尼亚响尾蛇毒液诱导的细胞毒性和炎症。

Cytotoxicity and inflammation induced by Philodryas patagoniensis venom.

机构信息

Programa de Pós-Graduação em Bioquímica, Universidade Federal do Pampa, Uruguaiana, RS, Brazil.

Programa de Pós-Graduação em Educação em Ciências: Química da Vida e Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2022 Jul;257:109356. doi: 10.1016/j.cbpc.2022.109356. Epub 2022 Apr 29.

Abstract

The Green racer Philodryas patagoniensis is a snake species from South America and accidents with this genus are often neglected. Therefore, this study aimed to evaluate the toxicological, cytotoxic, and inflammatory potential of P. patagoniensis venom (PpV). The experimental model Artemia salina was used to determine toxicity through the median lethal dose (LD). Cell viability and genotoxicity were evaluated in human mononuclear cells using the Trypan blue test and the Comet assay, respectively. To assess inflammation, mice had the ventral surface of the right hind paw injected with saline, formalin, and three different concentrations of venom (1, 1.5, and 2 μg. 50 μL). LD in A. salina was 461 μg. mL. PpV caused a significant increase in cell death and genotoxicity in human mononuclear cells at two concentrations (575 and 1150 μg. mL). PpV shown also to be a strong agent causing nociception in mice. Paw edema totaled four days at 1.5 μg. 50 μL. The hyperalgesia caused by the venom had a long duration in mice, lasting eight days at all concentrations evaluated. Thus, we evaluated for the first time the toxicological potential of PpV in A. salina model and in leukocytes. We concluded that systemic oxidative stress, which we infer to be in the genesis of cytotoxicity and genotoxicity observed in vitro, and the inflammatory process are part of the pathways that trigger the venom damage cascades. Relevant data for both scientific research and clinical medicine. Nonetheless, studies are needed to elucidate these mechanisms.

摘要

绿曼巴 Philodryas patagoniensis 是一种来自南美洲的蛇类,其相关的事故经常被忽视。因此,本研究旨在评估 P. patagoniensis 毒液(PpV)的毒理学、细胞毒性和炎症潜力。使用卤虫 Artemia salina 实验模型通过半数致死剂量(LD)来确定毒性。使用台盼蓝试验和彗星试验分别评估人单核细胞的细胞活力和遗传毒性。为了评估炎症,向小鼠右后爪腹侧表面注射盐水、福马林和三种不同浓度的毒液(1、1.5 和 2μg.50μL)。A. salina 的 LD 为 461μg. mL。PpV 在两个浓度(575 和 1150μg. mL)下导致人单核细胞死亡和遗传毒性显著增加。PpV 还被证明是一种强烈的致痛剂,可引起小鼠疼痛。在 1.5μg.50μL 时,爪子肿胀持续了四天。毒液引起的痛觉过敏在小鼠中持续时间长,在所有评估浓度下持续八天。因此,我们首次在 A. salina 模型和白细胞中评估了 PpV 的毒理学潜力。我们得出结论,全身氧化应激,我们推断这是体外观察到的细胞毒性和遗传毒性的发生机制,以及炎症过程,是触发毒液损伤级联的途径的一部分。这些数据对科学研究和临床医学都很重要。然而,仍需要研究来阐明这些机制。

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