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DNA 抑制尖吻蝮蛇毒,一种有前途的蛇伤治疗分子。

Inhibition of Echis carinatus venom by DNA, a promising therapeutic molecule for snakebite management.

机构信息

DOS in Biochemistry, University of Mysore, Manasagangotri, Mysuru 570 006, India.

Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.

出版信息

Biochim Biophys Acta Gen Subj. 2018 May;1862(5):1115-1125. doi: 10.1016/j.bbagen.2018.02.003. Epub 2018 Feb 7.

Abstract

BACKGROUND

E. carinatus bite is a serious threat to South-Asian countries including India, as it causes the highest number of deaths and debilitating sustained tissue necrosis at the bite site. One of our previous studies has demonstrated the strong interaction between DNA and E. carinatus venom. Therefore, in this study, the effect of DNA on E. carinatus venom has been examined.

METHODS

Here we show that calf thymus DNA interact strongly with E. carinatus venom and inhibits its enzymatic and pharmacological activities such as proteolytic, hemolytic, hyaluronidase, L-amino acid oxidase, NETosis, hemorrhage, pro-coagulant, and lethality. Further, using immunoblots and immunofluorescence, the study demonstrates the inhibition of proteolytic cleavage of several surface receptors on PMNs, PBMCs, and platelets by the DNA.

CONCLUSIONS

This study for the first time explored the efficient inhibition of enzymatic, pharmacological and lethal properties of E. carinatus venom by the naked DNA and demonstrates the possible therapeutic application of it during snakebite management.

GENERAL SIGNIFICANCE

This study identifies naked DNA as an effective defense weapon that has got the therapeutic potential to inhibit the detrimental effects of E. carinatus bite.

摘要

背景

E. carinatus 咬伤对包括印度在内的南亚国家构成严重威胁,因为它会导致死亡人数最多,并在咬伤部位造成持续的组织坏死。我们之前的一项研究表明 DNA 与 E. carinatus 毒液之间存在强烈的相互作用。因此,在这项研究中,研究了 DNA 对 E. carinatus 毒液的影响。

方法

我们在这里表明,小牛胸腺 DNA 与 E. carinatus 毒液强烈相互作用,并抑制其酶和药理学活性,如蛋白水解、溶血、透明质酸酶、L-氨基酸氧化酶、NETosis、出血、促凝和致死性。此外,通过免疫印迹和免疫荧光,研究表明 DNA 抑制了 PMNs、PBMCs 和血小板上几种表面受体的蛋白水解切割。

结论

这项研究首次探索了裸露 DNA 对 E. carinatus 毒液的酶、药理和致死特性的有效抑制,并证明了它在蛇咬伤管理中的潜在治疗应用。

一般意义

这项研究确定了裸露的 DNA 是一种有效的防御武器,具有抑制 E. carinatus 咬伤的有害影响的治疗潜力。

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