Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities.
Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities.
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DOI：
10.1016/j.biopha.2022.113900
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发表时间：
2022-10
期刊：
影响因子：
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通讯作者：
Qi Lian;Lipeng Zhong;Kepu Fu;Yuxin Ji;Xiangyue Zhang;Chunju Liu;Chunhong Huang
中科院分区：
文献类型：
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作者：
Qi Lian;Lipeng Zhong;Kepu Fu;Yuxin Ji;Xiangyue Zhang;Chunju Liu;Chunhong Huang
Snake venom is considered a “toxin arsenal”, and it often induces a series of clinical and pathophysiological symptoms in snakebite victims. Interestingly, toxin inhibitors are commonly found in the serum of snakes and their predators.Sinonatrix annularisis a type of non-venomous snake that was reported to contain an “inhibitor cocktail”, including phospholipase A2inhibitors (PLIs), metalloproteinase inhibitors (SVMPIs), and small serum protein (SSP). However, the sequences and activities of these components remain obscure. In this study, we performed envenomation challenges onS. annularisusing venoms fromDeinagkistrodon acutus,Agkistrodon halysandNaja atra. In brief, the maximum injected amount of venom was 360 mg/kg forD. acutus, 72 mg/kg forA. halys, and 18 mg/kg forN. atra. The mRNA expression of the inhibitors PLIα, PLIβ, PLIγ, SVMPI, serpin A1, and SSP showed a dose-dependent effect on envenomation. Liver homogenate fromS. annularis(LH) was prepared and used to evaluate its inhibitory effect on snake venoms. As a result, LH showed significant neutralization of venom PLA2, mitigated hemorrhage, venom-induced muscle damage, and system toxicity. In the presence of LH, envenomated mice exhibited attenuated inflammation, apoptosis, oxidative damage, and mitigated changes in serum biochemical markers caused by venom. The study reveals the secret of “natural immunity” in snakes, namely, the “antivenom”, which consists of an inhibitor proteome or cocktail.
