Barietin, a snake venom vascular endothelial growth factor from puff adder Bitis arietans venom, increases the heart rate with minor effect on blood pressure in rats

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  Barietin, a snake venom vascular endothelial growth factor from puff adder Bitis arietans venom, increases the heart rate with minor effect on blood pressure in rats ABSTRACT Snake venom vascular endothelial growth factors (svVEGFs) are homodimeric proteins comprising two equal subunits bound by two intermolecular disulfide bonds. The main biological effects of svVEGFs are local vasodilatation, increasing of vascular permeability, and hypotension. Barietin, a svVEGF purified from the venom of puff adder Bitis arietans , differs from other representatives of this toxin family by its shortened C-terminal amino acid sequence. No data about barietin effects on hemodynamics are available. Studying those in rats we found that barietin at a dose of 1 mg/kg significantly increased heart rate, exerting only a minor influence on blood pressure. In this respect, it differs from other svVEGFs having a significant effect on blood pressure. We aimed to find the barietin active fragment which m...

Taking the sting out of scorpions: Electrophysiological investigation of the relative efficacy of three antivenoms against medically significant Centruroides species

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Taking the sting out of scorpions: Electrophysiological investigation of the relative efficacy of three antivenoms against medically significant Centruroides species

Abstract

In this study, we report the innovative application of whole-cell patch-clamp electrophysiology in assessing broad-spectrum neutralisation by three different antivenoms, of venoms from the medically significant scorpion genus Centruroides. Envenomations by as many as 21 species from the Centruroides genus result in up to 300,000 envenomations per year in Mexico, which poses significant and potentially life-threatening pathophysiology. We first evaluated the in vitro manifestation of envenomation against two human voltage-gated sodium (hNaV) channel subtypes: hNaV1.4 and hNaV1.5, which are primarily expressed in skeletal muscles and cardiomyocytes, respectively. The neutralisation of venom activity was then characterised for three different antivenoms using a direct competition model against the more potent target, hNaV1.4. While broad-spectrum neutralisation was identified, variation in neutralisation arose for Centruroides elegans, C. limpidus, C. noxius and C. suffusus venoms, despite the presence of a number of these venoms within the immunising mixture. This raises questions regarding the truly “broad” neutralisation capacity of the antivenoms. This study not only extends previous validation of the in vitro investigation of antivenom efficacy utilising the whole-cell patch-clamp technique but also underscores the potential of this animal-free model in exploring cross-reactivity, experimental scalability, and most importantly, informing clinical management practices regarding the administration of antivenom in Mexico.

Campbell, S. I., Chow, C. Y., Neri-Castro, E., Alagón, A., Gómez, A., Soria, R., King, G. F., & Fry, B. G. (2024). Taking the sting out of scorpions: Electrophysiological investigation of the relative efficacy of three antivenoms against medically significant Centruroides species. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 283, 109977. https://doi.org/10.1016/j.cbpc.2024.109977