Background

The use of venom fractions from the Iranian cobra could be useful adjunct treatments of malaria with chloroquine. A metabolomic investigation with ¹HNMR spectroscopy was conducted on an effective fraction tested earlier using Plasmodium berghei as an experimental murine model.

Purpose

We sought to ascertain both safety and anti-parasitic effects of experimental therapies.

Methods

After purification of the venom fractions, 25 mice were infected, then treated for 4 days with 0.2 ml of 5 mg/kg, 2.5 mg/kg and 1 mg/kg of the effective fraction, chloroquine, and a drug vehicle. An ED50 was obtained using Giemsa staining and real-time PCR analysis. The toxicity tests inspecting both liver and kidney tissues were performed.

Results

A clear inhibitory effect on parasitaemia was observed (with 75% inhibition with 5 mg/kg and 50% reduction when 2.5 mg/kg dosage used). ED50 obtained 2.5 mg/kg. The metabolomics were identified as differentiation of aminoacyl-t-RNA biosynthesis, valine, leucine, isoleucine biosynthesis and degradation pathways were observed.

Conclusion

Upon therapeutic effects of cobra venom fraction, further optimization of dose-dependent response of pharmacokinetics would be worthwhile for further exploration in adjunct experimental venom therapies.

中文翻译：

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用 1H 核磁共振波谱法研究白菖​​蒲有效馏分治疗白氏疟原虫小鼠血清的代谢组学特征

背景

使用来自伊朗眼镜蛇的毒液部分可能是有用的氯喹辅助治疗疟疾的方法。具有A代谢物组学调查^1个HNMR光谱上使用前面试验的有效分数进行疟原虫 柏氏疟原虫作为实验小鼠模型。

目的

我们试图确定实验疗法的安全性和抗寄生虫作用。

方法

毒液部分纯化后，感染 25 只小鼠，然后用 0.2 毫升 5 毫克/千克、2.5 毫克/千克和 1 毫克/千克的有效部分、氯喹和药物载体处理 4 天。使用吉姆萨染色和实时 PCR 分析获得 ED50。进行了检查肝和肾组织的毒性试验。

结果

观察到对寄生虫血症的明显抑制作用（5mg/kg 抑制 75%，2.5mg/kg 剂量降低 50%）。ED50 为 2.5mg/kg。代谢组学被鉴定为氨酰-t-RNA 生物合成的分化，观察到缬氨酸、亮氨酸、异亮氨酸生物合成和降解途径。

结论

根据眼镜蛇毒液的治疗效果，进一步优化药代动力学的剂量依赖性反应将值得在辅助实验性毒液治疗中进一步探索。