Local and systemic toxicity of Echis carinatus venom: neutralization by Cassia auriculata L. leaf methanol extract

Abstract

Viper bites cause high morbidity and mortality especially in tropical and subtropical regions, affecting a large number of the rural population in these areas. Even though anti-venoms are available, in most cases they fail to tackle viper venom-induced local manifestations that persist even after anti-venom administration. Several studies have been reported the use of plant products and approved drugs along side anti-venom therapy for efficient management of local tissue damage. In this regard, the present study focuses on the protective efficacy of Cassia auriculata L. (Leguminosae) against Echis carinatus venom (ECV) induced toxicity. C. auriculata is a traditional medicinal plant, much valued in alternative medicine for its wide usage in ayurveda, naturopathy, and herbal therapy. Further, it has been used widely by traditional healers for treatment of snake and scorpion bites in the Western Ghats of Karnataka, India. In the present study, C. auriculata leaf methanol extract (CAME) significantly inhibited enzymatic activities of ECV proteases (96 ± 1 %; P = 0.001), PLA2 (45 ± 5 %; P = 0.01) and hyaluronidases (100 %; P = 0.0003) in vitro and hemorrhage, edema and myotoxicity in vivo. Further, CAME effectively reduced the lethal potency of ECV and increased the survival time of mice by ~6 times (17 vs 3 h). These inhibitory potentials of CAME towards hydrolytic enzymes, mortal and morbid symptoms of ECV toxins clearly substantiates the use by traditional healers of C. auriculata as a folk medicinal remedy for snakebite.

Tumescent contravenom: murine model for prehospital treatment of Naja naja neurotoxic snake envenomation

“…Snake venoms typically contain hyaluronidase. Adding a hyaluronidase‐inhibitor to a tumescent contravenom solution might limit the extent of venom diffusion beyond the snakebite site and delay systemic absorption of venom and limit the spread of venom within local tissues …”

Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin

“…Orchestrated action of locally acting, cell and/or matrix degrading principle toxins (Zn 2+ MPs, PLA 2 s and HYs) present in ECV [ 7 ] are mainly responsible for severe local toxicity of E . carinatus bite.…”

“…Over last decade, several studies have been reported the use of plant extracts, phytochemicals and clinically approved drugs to neutralize viper venom induced local toxicity via pre-incubation method. However, few demonstrate the neutralization of local/systemic toxicity both by co and independent injection experiments using murine model [ 7 , 15 , 49 ].…”

“…Local toxicity induced by venomous viperid or crotalid bites is never the less a pathological condition, caused by mixture of toxins rather than a single toxin present in the venom. Hence, treatment of venom induced progressive tissue damage, that persists even after anti-snake venom (ASV) administration is still a challenging issue for the existing strategies of snakebite management [ 7 ].…”

“…At the outset Zn 2+ metalloproteases, also called as snake venom metalloproteases (SVMPs) were mainly blamed for such complications, as they degrade proteins of extra cellular matrix (ECM), basement membrane and blood coagulation cascade, resulting in a wide range of hemostatic alterations and local tissue damage [ 8 ]. However, in the recent past, besides SVMPs, other key hydrolytic enzymes such as snake venom phospholipase A 2 s (SVPLA 2 s) and snake venom hyaluronidases (SVHYs) are also known to induce local tissue damage [ 7 , 9 – 11 ]. SVPLA 2 s can be catalytically active forms (Asp49) or inactive variants (Lys49).…”