Investigation of the inhibitory potential of phospholipase A2 inhibitor gamma from Sinonatrix annularis to snake envenomation

Xiong, Shengwei; Luo, Yun; Zhong, Liang; Xiao, Huixiang; Hong, Pan; Liao, Keren; Yang, Mengxue; Huang, Chunhong

doi:10.1016/j.toxicon.2017.07.019

Cited by 16 publications

(7 citation statements)

References 28 publications

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“…Venom derived from D. acutus and A. halys were also myotoxic, and caused 52% and 31% desmin loss, respectively. Desmin degradation was previously reported in Notechis scutatus snake envenomation [ 29 ], and could be attenuated by snake endogenous PLIγ (gamma type PLA2 inhibitor protein) [ 28 ]. The breakdown of desmin was further demonstrated by immunohistological evaluation.…”

Section: Discussionmentioning

confidence: 99%

“…The PLA 2 family has recently been regarded a promising target for broad spectrum antivenom drug development, due to their wide-distribution, high content, and diverse toxicological effects [ 25 ]. Previous studies revealed that PLA 2 s acts with other toxic components in a synergistic manner, mostly zinc-dependent metalloproteinases, which are responsible for hemorrhage, blistering, and necrosis [ 26 , 27 , 28 ]. The anti-PLA 2 IgGs developed from Ba spII RP4 PLA 2 (a non-toxic PLA 2 from Bothrops alternates venom) could inhibit haemolysis and myotoxicity of the crude venom, and also decreased 50% of mortality of mice dosed with four times the LD 50 .…”

Section: Discussionmentioning

confidence: 99%

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Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Wang

Zhang

et al. 2018

Molecules

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Phospholipase A2s (PLA2) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA2s, and was recently repurposed to a broad-spectrum inhibitor of PLA2 in snake venom. To evaluate the protective abilities of varespladib to hemorrhage, myonecrosis, and systemic toxicities that are inflicted by different crude snake venoms, subcutaneous ecchymosis, muscle damage, and biochemical variation in serum enzymes derived from the envenomed mice were determined, respectively. Varespladib treatment showed a significant inhibitory effect to snake venom PLA2, which was estimated by IC50 in vitro and ED50 in vivo. In animal models, the severely hemorrhagic toxicity of D. acutus and A. halys venom was almost fully inhibited after administration of varespladib. Moreover, signs of edema in gastrocnemius muscle were remarkably attenuated by administration of varespladib, with a reduced loss of myonecrosis and desmin. Serum levels of creatine kinase, lactate dehydrogenase isoenzyme 1, aspartate transaminase, and alanine transaminase were down-regulated after treatment with varespladib, which indicated the protection to viscera injury. In conclusion, varespladib may be a potential first-line drug candidate in snakebite envenomation first aid or clinical therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Wang

Zhang

et al. 2018

Molecules

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“…Venom synergistic effect is mainly revealed by the research of venom purification and molecular mechanisms. For example, SVMP may interact with phospholipase A 2 (Xiong et al, 2017). The enzyme activity of P-III metalloproteinase complex was regulated by its subunits (Doley and Kini, 2009).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Proteinase Activity by Purification and Identification of Toxic Protease From Nemopilema nomurai

Yin

et al. 2021

Front. Pharmacol.

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Scyphozoan Nemopilema nomurai envenomation is an unresolved threat to human health in Asian waters. Nemopilema nomurai venom metalloproteinases show important toxicities in skin damage and inflammation, but there is still no purified protein for further studies. In this study, high proteinase activity fractions in tentacle autolysis were isolated by ammonium sulfate precipitation, DEAE Sepharose Fast Flow, and Superdex 75 chromatography successively. Purification was guided by azocasein hydrolysis activity and SDS-PAGE. The final products were analyzed by LC-MS/MS. Four elution peaks purified by Superdex 75 chromatography had multiple protein bands but did not show proteinase activity. These fractions would recover proteinase activity after mixing again. Regulation mechanisms were speculated as binding metalloproteinase regulator or disaggregating metalloproteinase inhibitor by LC-MS/MS analysis. For the first time, a synergistic effect in N. nomurai proteinase activity was found in the purification process.

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“…Most inhibitors extracted from medical plants, marine animals, and mammalian serum specially inhibit svPLA 2 toxicity. sbPLIs are natural, endogenous protective components against snake venom, among which the γ PLI were commonly inhibitive to different category of venoms [ 100 ]. Anti-PLA 2 antibodies could specifically inactivate enzymatic activity and toxicity, both with the original venom and other svPLA 2 s [ 93 ].…”

Section: Discussionmentioning

confidence: 99%

Snake Venom PLA₂, a Promising Target for Broad-Spectrum Antivenom Drug Development

Xiao

Hong

Liao

et al. 2017

BioMed Research International

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Snakebite envenomation is a neglected global health problem, causing substantial mortality, disability, and psychological morbidity, especially in rural tropical and subtropical zones. Antivenin is currently the only specific medicine for envenomation. However, it is restricted by cold storage, snakebite diagnosis, and high price. Snake venom phospholipase A2s (svPLA2s) are found in all kinds of venomous snake families (e.g., Viperidae, Elapidae, and Colubridae). Along with their catalytic activity, svPLA2s elicit a wide variety of pharmacological effects that play a pivotal role in envenomation damage. Hence, neutralization of the svPLA2s could weaken or inhibit toxic damage. Here we overviewed the latest knowledge on the distribution, pathophysiological effects, and inhibitors of svPLA2s to elucidate the potential for a novel, wide spectrum antivenom drug targeting svPLA2s.

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Investigation of the inhibitory potential of phospholipase A2 inhibitor gamma from Sinonatrix annularis to snake envenomation

Cited by 16 publications

References 28 publications

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Synergistic Effect of Proteinase Activity by Purification and Identification of Toxic Protease From Nemopilema nomurai

Snake Venom PLA₂, a Promising Target for Broad-Spectrum Antivenom Drug Development

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Investigation of the inhibitory potential of phospholipase A2 inhibitor gamma from Sinonatrix annularis to snake envenomation

Cited by 16 publications

References 28 publications

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Synergistic Effect of Proteinase Activity by Purification and Identification of Toxic Protease From Nemopilema nomurai

Snake Venom PLA2, a Promising Target for Broad-Spectrum Antivenom Drug Development

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Snake Venom PLA₂, a Promising Target for Broad-Spectrum Antivenom Drug Development