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. 2021 Dec:250:109186.
doi: 10.1016/j.cbpc.2021.109186. Epub 2021 Sep 9.

Capillary leak syndrome induced by the venoms of Russell's Vipers (Daboia russelii and Daboia siamensis) from eight locales and neutralization of the differential toxicity by three snake antivenoms

Thava Malar Changra Lingam  1 , Kae Yi Tan  1 , Choo Hock Tan  2
Affiliations

Capillary leak syndrome induced by the venoms of Russell's Vipers (Daboia russelii and Daboia siamensis) from eight locales and neutralization of the differential toxicity by three snake antivenoms

Thava Malar Changra Lingam et al. Comp Biochem Physiol C Toxicol Pharmacol. 2021 Dec.

Abstract

Snakebite envenomation caused by the Western and Eastern Russell's Vipers (Daboia russelii and Daboia siamensis) may potentially induce capillary leak syndrome (CLS), while the use of antivenom in treating this has not been well examined. This study investigated the CLS-inducing toxicity of Russell's Viper venoms from various sources and examined the neutralization activity of regionally available antivenoms, using a newly devised mouse model. D. russelii venoms demonstrated a more consistent vascular leakage activity (76,000-86,000 CLS unit of vascular leak index, a function of the diameter and intensity of Evans Blue dye extravasation into dermis) than D. siamensis venoms (33,000-88,000 CLS unit). Both species venoms increased hematocrits markedly (53-67%), indicating hemoconcentration. Regional antivenoms (DsMAV-Thailand, DsMAV-Taiwan, VPAV-India) preincubated with the venoms effectively neutralized the CLS effect to different extents. When the antivenoms were administered intravenously post-envenomation (challenge-rescue model), the neutralization was less effective, implying that CLS has a rapid onset that preceded the neutralizing activity of antivenom, and/or the antivenom has limited biodistribution to the venom's inoculation site. In conclusion, Russell's Viper venoms of both species from various locales induced CLS in mice. Antivenoms generally had limited efficacy in neutralizing the CLS effect. Innovative treatment for venom-induced CLS is needed.

Keywords: Capillary leak syndrome; Daboia russelii; Daboia siamensis; Hematocrit; Snakebite envenomation; Vascular permeability.

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