<p><?tk 2?>Snake envenomation, a neglected tropical disease, presents complex and species-dependent systemic pathophysiology. Here, we conduct an integrated proteomic and in vivo toxicological assessment of venoms from ten medically significant Chinese snakes. Our proteomic analysis delineated the venom composition of the ten snake species. Viperidae venoms were rich in snake venom metalloproteinases and phospholipase A<sub>2</sub>, consistent with their hemorrhagic and myotoxic effects, while elapidae venoms were dominated by three-finger toxin and phospholipase A<sub>2</sub>. Furthermore, we identified that the colubrid <i>Rhabdophis tigrinus</i> possesses a unique venom arsenal primarily composed of three-finger toxin (33.1%) and phospholipase A<sub>2</sub> (30.8%). In vivo toxicity assessment in mice via four administration routes (subcutaneous, intramuscular, intraperitoneal, intravenous) demonstrated that venom lethality was highly route-dependent, with elapid venoms (particularly <i>Bungarus multicinctus</i>, intravenous median lethal dose = 0.16&#xa0;mg/kg) being an order of magnitude more potent than viperid venoms. Notably, the injection route critically modulated the toxicological manifestations; for instance, intramuscular injection accentuated local tissue damage, while intravenous injection exacerbated coagulopathy. This multi-omics study systematically links the specific toxin arsenals of these ten venoms to distinct pathological phenotypes observed via different clinically relevant routes, providing a valuable resource for understanding venom toxicity mechanisms and guiding clinical management of snakebite.</p>

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Toxicological profiling of venoms from ten major Chinese snakes: a mass spectrometry-based proteomic and multiroute assessment

  • Jianqi Zhao,
  • Linfeng Wang,
  • Xiao Shi,
  • Yang Yang,
  • Chunhong Huang

摘要

Snake envenomation, a neglected tropical disease, presents complex and species-dependent systemic pathophysiology. Here, we conduct an integrated proteomic and in vivo toxicological assessment of venoms from ten medically significant Chinese snakes. Our proteomic analysis delineated the venom composition of the ten snake species. Viperidae venoms were rich in snake venom metalloproteinases and phospholipase A2, consistent with their hemorrhagic and myotoxic effects, while elapidae venoms were dominated by three-finger toxin and phospholipase A2. Furthermore, we identified that the colubrid Rhabdophis tigrinus possesses a unique venom arsenal primarily composed of three-finger toxin (33.1%) and phospholipase A2 (30.8%). In vivo toxicity assessment in mice via four administration routes (subcutaneous, intramuscular, intraperitoneal, intravenous) demonstrated that venom lethality was highly route-dependent, with elapid venoms (particularly Bungarus multicinctus, intravenous median lethal dose = 0.16 mg/kg) being an order of magnitude more potent than viperid venoms. Notably, the injection route critically modulated the toxicological manifestations; for instance, intramuscular injection accentuated local tissue damage, while intravenous injection exacerbated coagulopathy. This multi-omics study systematically links the specific toxin arsenals of these ten venoms to distinct pathological phenotypes observed via different clinically relevant routes, providing a valuable resource for understanding venom toxicity mechanisms and guiding clinical management of snakebite.