Inhibition of key enzymes linked to snake venom induced local tissue damage by kolaviron

Abstract

Abstract Objectives Snakebite envenoming is an important public health problem that threatens the lives of healthy individuals especially in many tropical countries like Nigeria. Antivenins, the only efficient approach for snakebite envenoming, are limited in their efficacy in the neutralization of local tissue damage. Snake venom phospholipase A2 (PLA2), protease, hyaluronidase and l-amino acid oxidase (LAAO) are the major hydrolytic enzymes involve in local tissue damage. Therefore, this study evaluates the inhibitory effect of kolaviron (KV) against Naja n. nigricollis (NNN) snake venom hydrolytic enzymes involved in local tissue damage. Methods Kolaviron was evaluated for its ability to inhibit the hydrolytic enzyme activities of NNN venom phospholipase A2 (PLA2), protease, hyaluronidase and l-amino acid oxidase (LAAO). Present study also deals with the neutralization of NNN venom enzyme(s) induced complications such as myotoxic, edemic, hemolytic and procoagulant effects. Results Kolaviron inhibited the PLA2, protease, hyaluronidase and LAAO enzyme activities of NNN venom in a dose-dependent manner. Furthermore, myotoxic, edemic, hemolytic and procoagulant effects induced by NNN venom enzyme were neutralized significantly (p<0.05) when different doses of KV were pre-incubated with venom before assays. Conclusions These findings clearly present kolaviron as a potent inhibitor against NNN venom hydrolytic enzymes involved in local tissue damage and may act by either forming an inhibitor-enzyme complex that restricts the substrate availability to the enzyme or direct binding to the enzyme active site that affects the enzyme activity thereby mitigating venom-induced toxicity.