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东南亚两种鲜为人知的树栖蝰蛇——维氏竹叶青和红竹叶青的蛇毒毒性及交叉中和作用

Toxicity and cross-neutralization of snake venoms from two lesser-known arboreal pit vipers in Southeast Asia: Trimeresurus wiroti and Trimeresurus puniceus.

作者信息

Lee Louisa Pernee, Tan Kae Yi, Tan Choo Hock

机构信息

Venom Research & Toxicology Lab, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Protein and Interactomics Laboratory, Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

Toxicon. 2020 Oct 15;185:91-96. doi: 10.1016/j.toxicon.2020.06.012. Epub 2020 Jun 22.

Abstract

The lesser-known Sundaic lance-headed pit vipers Trimeresurus wiroti (Malaysia) and Trimeresurus puniceus (Indonesia) contribute to the disease burden of snakebite envenomation in Southeast Asia, but their venom toxicity and neutralization remain insufficiently investigated. This study demonstrated that both venoms were procoagulant (involving thrombin-like activity), hemorrhagic, and lethal to mice, with T. wiroti venom being more lethal (LD = 0.78 μg/g c.f. 1.21 μg/g). The hetero-specific antivenom from Thailand, Green Pit Viper Antivenom (GPVAV, raised against Trimeresurus albolabris) cross-reacted with T. wiroti and T. puniceus venoms with a higher efficacy of immunological binding activity for the latter. The antivenom was also effective in cross-neutralizing the procoagulant, hemorrhagic and lethal effects of the venoms. In lethality neutralization, GPVAV showed a potency of 0.79-1.05 mg venom per mL antivenom, corresponding to the complete neutralization of approximately 8-10 mg venom per unit vial of antivenom for T. wiroti and T. puniceus venoms. Taken together, it was inferred that T. wiroti, T. puniceus, and T. albolabris venoms share common toxin epitopes, thus enabling the cross-neutralization observed. These findings suggest that GPVAV may be potentially useful in the management of envenomation by T. wiroti and T. puniceus while awaiting clinical trial and validation.

摘要

鲜为人知的巽他竹叶青属(Sundaic)的白唇竹叶青(Trimeresurus wiroti,分布于马来西亚)和紫棕竹叶青(Trimeresurus puniceus,分布于印度尼西亚)是东南亚蛇咬伤中毒疾病负担的成因之一,但其毒液毒性和中和作用仍未得到充分研究。本研究表明,这两种毒液均具有促凝血作用(涉及类凝血酶活性)、出血性,且对小鼠具有致死性,其中白唇竹叶青毒液的致死性更强(半数致死量LD = 0.78 μg/g,相比之下,紫棕竹叶青毒液的LD为1.21 μg/g)。来自泰国的异源特异性抗蛇毒血清,即绿竹叶青抗蛇毒血清(GPVAV,针对白唇竹叶青制备)与白唇竹叶青和紫棕竹叶青毒液发生交叉反应,且对后者的免疫结合活性效力更高。该抗蛇毒血清在交叉中和毒液的促凝血、出血和致死作用方面也有效。在致死性中和方面,GPVAV表现出每毫升抗蛇毒血清可中和0.79 - 1.05毫克毒液的效力,相当于每瓶抗蛇毒血清可完全中和约8 - 10毫克白唇竹叶青和紫棕竹叶青毒液。综上所述,推断白唇竹叶青、紫棕竹叶青和白唇竹叶青毒液具有共同的毒素表位,因此能够观察到交叉中和现象。这些研究结果表明,在等待临床试验和验证期间,GPVAV可能对白唇竹叶青和紫棕竹叶青咬伤中毒的治疗具有潜在作用。

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