从处女锥虫毒素中寻找候选分子以开发新的生物药物。

Anas A Mohamed, Zohour I Nabil, Mohamed S El-Naggar
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摘要

背景:本研究采用药理学和生物医学相结合的方法,对圆锥蛇粗毒液的生物活性进行研究,以确定其潜在的药理价值及其体内作用机制。方法:采用1/5、1/10 LC50、9.14、4.57 mg/kg两种剂量(LC50的1/5、1/10、9.14、4.57 mg/kg)对实验动物进行药理学试验(中枢和外周镇痛、抗炎、解热),采用1/2 LC50 (22.85 mg/kg)不同时间间隔对实验动物进行细胞毒性试验,并与对照组和参比组进行比较。结果:与对照组相比,毒液处理小鼠尾部浸泡时间明显增加。此外,与对照组相比,注射两种毒液剂量后,扭动运动显著减少。此外,只有高浓度的毒液在炎症晚期才有轻微的抗炎作用。两种毒剂量均可显著降低小鼠的发热。另一方面,给毒后脂质过氧化(4小时)显著增加,谷胱甘肽含量和谷胱甘肽过氧化物酶活性显著降低,而脂质过氧化和一氧化氮含量(24小时)和过氧化氢酶活性显著降低。结论:这些结果表明,蛇尾蛇粗毒液可能含有具有低细胞毒作用的药理活性成分。因此,它可能包含一种潜在的先导化合物,用于开发控制疼痛和发热的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Prospecting for candidate molecules from Conus virgo toxins to develop new biopharmaceuticals.

Background: A combination of pharmacological and biomedical assays was applied in this study to examine the bioactivity of Conus virgo crude venom in order to determine the potential pharmacological benefit of this venom, and its in vivo mechanism of action.

Methods: Two doses (1/5 and 1/10 of LC50, 9.14 and 4.57 mg/kg) of the venom were used in pharmacological assays (central and peripheral analgesic, anti-inflammatory and antipyretic), while 1/2 of LC50 (22.85 mg/kg) was used in cytotoxic assays on experimental animals at different time intervals, and then compared with control and reference drug groups.

Results: The tail immersion time was significantly increased in venom-treated mice compared with the control group. Also, a significant reduction in writhing movement was recorded after injection of both venom doses compared with the control group. In addition, only the high venom concentration has a mild anti-inflammatory effect at the late inflammation stage. The induced pyrexia was also decreased significantly after treatment with both venom doses. On the other hand, significant increases were observed in lipid peroxidation (after 4 hours) and reduced glutathione contents and glutathione peroxidase activity, while contents of lipid peroxidation and nitric oxide (after 24 hours) and catalase activity were depleted significantly after venom administration.

Conclusion: These results indicated that the crude venom of Conus virgo probably contain bioactive components that have pharmacological activities with low cytotoxic effects. Therefore, it may comprise a potential lead compound for the development of drugs that would control pain and pyrexia.

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来源期刊
CiteScore
4.80
自引率
8.30%
发文量
39
审稿时长
6-12 weeks
期刊介绍: Journal of Venomous Animals and Toxins including Tropical Diseases (JVATiTD) is a non-commercial academic open access publication dedicated to research on all aspects of toxinology, venomous animals and tropical diseases. Its interdisciplinary content includes original scientific articles covering research on toxins derived from animals, plants and microorganisms. Topics of interest include, but are not limited to:systematics and morphology of venomous animals;physiology, biochemistry, pharmacology and immunology of toxins;epidemiology, clinical aspects and treatment of envenoming by different animals, plants and microorganisms;development and evaluation of antivenoms and toxin-derivative products;epidemiology, clinical aspects and treatment of tropical diseases (caused by virus, bacteria, algae, fungi and parasites) including the neglected tropical diseases (NTDs) defined by the World Health Organization.
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