Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities

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 annularis is a type of non-venomous snake that was reported to contain an inhibitor cocktail, including phospholipase A2 inhibitors (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 on S. annularis using venoms from Deinaglcistrodon acutus, Aglcistrodon halys and Naja atra. In brief, the maximum injected amount of venom was 360 mg/kg for D. acutus, 72 mg/kg for A. halys, and 18 mg/kg for N. atra. The mRNA expression of the inhibitors PLI alpha, PLI beta, PLI gamma, SVMPI, serpin A1, and SSP showed a dose-dependent effect on envenomation. Liver homogenate from S. 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.

Automated summary

Snake venom is a toxic arsenal that induces various symptoms in snakebite victims. This study reveals the presence of inhibitor cocktail in non-venomous snakes, which can neutralize snake venoms and mitigate venom-induced damage.