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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. [ABSTRACT FROM AUTHOR]

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. Reference 1 Wang Y., Zhang J., Zhang D., Xiao H., Xiong S., Huang C. Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. The authors would like to correct an error in the original publication [[1]]. [Extracted from the article]

Snake venom is a complex cocktail of toxins which induces a series of clinical and pathophysiological manifestations in victims, including severe local tissue damage and systemic alterations. Deinagkistrodon acutus (D. acutus) ranks among the “big four” life-threatening venomous species in China, whose venom possesses strong myotoxicity and hematotoxicity that often lead to permanent disability or muscle atrophy. Varespladib, an inhibitor of mammalian phospholipase A2 (PLA2), has been recently reproposed as an effective antidote against snakebite envenomation. The present study aimed at evaluating the protective role of varespladib on muscle regeneration in envenomed mice. Mice were grouped and subjected to inoculation with D. acutus venom or a mixture of venom and varespladib or control vehicle in the gastrocnemius muscle. Local injuries including hemorrhage, myonecrosis, ulceration, and systemic damages including general dysfunction, visceral failure, and inflammatory responses were observed at 1, 3, 7, 14, and 21 days. The results indicated that most of the muscle myonecrosis and hemorrhage were alleviated by varespladib. Besides, the pretreated mice recovered rapidly with lesser atrophy and muscle fibrosis. In conclusion, the findings of the present study suggested that varespladib is an effective antidote that could neutralize D. acutus venom and allow for earlier and improved rehabilitation outcome. [ABSTRACT FROM AUTHOR]

In order to get a better understanding of protein association during Solanum tuberosum (cv. Sarpo Mira)–Phytophthora infestans incompatible interaction, we investigated the proteome dynamics of cv. Sarpo Mira, after foliar application of zoospore suspension from P. infestans isolate, at three key time-points: zero hours post inoculation (hpi) (Control), 48 hpi (EI), and 120 hpi (LI); divided into early and late disease stages by the tandem mass tagging (TMT) method. A total of 1229 differentially-expressed proteins (DEPs) were identified in cv. Sarpo Mira in a pairwise comparison of the two disease stages, including commonly shared DEPs, specific DEPs in early and late disease stages, respectively. Over 80% of the changes in protein abundance were up-regulated in the early stages of infection, whereas more DEPs (61%) were down-regulated in the later disease stage. Expression patterns, functional category, and enrichment tests highlighted significant coordination and enrichment of cell wall-associated defense response proteins during the early stage of infection. The late stage was characterized by a cellular protein modification process, membrane protein complex formation, and cell death induction. These results, together with phenotypic observations, provide further insight into the molecular mechanism of P. infestans resistance in potatos. [ABSTRACT FROM AUTHOR]