Proteomic diversity of Russell's viper venom: exploring PLA2 isoforms, pharmacological effects, and inhibitory approaches

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(11), P. 3569 - 3584

Published: Aug. 24, 2024

Abstract Snakebite envenomation is a serious health concern in tropical regions, resulting high mortality. The World Health Organization (WHO) has declared it neglected disease and working on strategies to reduce Russell’s viper ( Daboia russelii ) one of the most abundant venomous snakes found across Southeast Asia. Proteomic analysis venom demonstrated variation, with phospholipase A2 (PLA2) being toxin geographic boundaries. PLA2, major constituent low-molecular-weight fraction snake venom, hydrolyses phospholipids at sn-2 position, releasing arachidonic acid lysophospholipids. They are reported cause various pharmacological effects, including hemolysis, anticoagulation, neurotoxicity, myotoxicity, oedema. Though administration antivenoms (ASV) primary treatment for envenomation, many drawbacks. Besides causing hypersensitivity reactions life-threatening anaphylaxis, ASV further complicated due its inability neutralize toxins. Thus, there greater need produce next-generation that can target specific toxins venom. In this review, we explored classification variation proteomic profile Asia date. addition, have also summarized mechanism action PLA2 discussed isoforms different regions their respective effects. Finally, drawbacks commercially available molecules investigated inhibiting toxin, discussed.

Language: Английский

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Snake Venom Pharmacokinetics and Acute Toxic Outcomes Following Daboia siamensis Envenoming: Experimental and Clinical Correlations

Toxins, Journal Year: 2024, Volume and Issue: 17(1), P. 10 - 10

Published: Dec. 29, 2024

An understanding of snake venom pharmacokinetics is essential for determining clinical outcomes envenoming and developing therapeutic approaches to the treatment envenoming, especially regarding timing optimal dosage antivenom administration. Daboia siamensis (Eastern Russell’s viper) causes systemic coagulopathy severe hemorrhage including acute kidney injury. These toxic can be diminished by administration high quantities viper antivenom. This study aimed determine correlation between profiles D. envenomed patients experimental data measuring plasma concentration conducting histopathological analyses heart, kidney, liver tissues in rats 6 h after envenomation. Intramuscular (i.m.) anesthetized (200 µg/kg) resulted a rapid absorption which reached peak at 60 min before declining then plateauing. Urine samples detected 209.3 ± 21.6 ng/mL following i.m. h. Histopathological studies showed morphological changes 3 exhibited higher degree severity A retrospective profile laboratory examination Central Thailand was also evaluated, showing that local effects were commonly observed early stage envenoming. abnormal increase creatinine levels found 13.6% population. Early specific within 1–2 highly recommended prevent life-threatening such as coagulation

Language: Английский

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Isolation and Pharmacological Characterisation of Pre-Synaptic Neurotoxins from Thai and Javanese Russell’s Viper (Daboia siamensis) Venoms

Toxins, Journal Year: 2024, Volume and Issue: 16(9), P. 405 - 405

Published: Sept. 19, 2024

The widespread geographical distribution of Russell’s vipers (Daboia spp.) is associated with marked variations in the clinical outcomes envenoming by species from different countries. This likely to be due differences quantity and potency key toxins and, potentially, presence or absence some venoms across spectrum. In this study, we aimed isolate pharmacologically characterise major neurotoxic components D. siamensis Thailand Java (Indonesia) explore efficacy antivenom a PLA2 inhibitor, Varespladib, against neuromuscular activity. These data will provide insights into link between venom outcomes, as well potential treatment strategies. Venoms were fractionated using RP-HPLC vitro activity isolated assessed chick biventer cervicis nerve-muscle preparation. Two fractions (i.e., 8 10) each venom. Fraction both produced pre-synaptic neurotoxicity myotoxicity, whereas fraction 10 was weakly neurotoxic. removal two abolished neurotoxicity, partially whole A combination that equivalent respective (10 µg/mL), but myotoxic effects not additive. (100 nM) prevented pre-administration Thai viper monovalent (2× recommended concentration) preincubation Varespladib nM). Additionally, reversed addition (100–300 60 min after fractions. present study demonstrates skeletal muscle Javanese are primarily

Language: Английский

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