Department of Medical Biochemistry, Cross River University of Technology, Calabar, Nigeria.
Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria.
J Basic Clin Physiol Pharmacol. 2020 Dec 14;32(6):1121-1130. doi: 10.1515/jbcpp-2020-0176.
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 A (PLA), 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 (NNN) snake venom hydrolytic enzymes involved in local tissue damage.
Kolaviron was evaluated for its ability to inhibit the hydrolytic enzyme activities of NNN venom phospholipase A (PLA), 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.
Kolaviron inhibited the PLA, 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.
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.
蛇伤是一个严重的公共卫生问题，尤其在尼日利亚等许多热带国家，它威胁着健康人群的生命。抗蛇毒血清是蛇伤的唯一有效治疗方法，但在中和局部组织损伤方面效果有限。蛇毒磷脂酶 A（PLA）、蛋白酶、透明质酸酶和 l-氨基酸氧化酶（LAAO）是导致局部组织损伤的主要水解酶。因此，本研究评估了 kolaviron（KV）对参与局部组织损伤的（NNN）蛇毒水解酶的抑制作用。
评估 kolaviron 抑制 NNN 毒液 PLA、蛋白酶、透明质酸酶和 LAAO 水解酶活性的能力。本研究还涉及中和 NNN 毒液酶引起的并发症，如肌毒性、水肿、溶血和促凝作用。
KV 以剂量依赖的方式抑制 NNN 毒液的 PLA、蛋白酶、透明质酸酶和 LAAO 酶活性。此外，当不同剂量的 KV 在测定前与毒液预孵育时，NNN 毒液酶诱导的肌毒性、水肿、溶血和促凝作用显著中和（p<0.05）。
这些发现清楚地表明 kolaviron 是一种有效的抑制剂，可抑制参与局部组织损伤的 NNN 毒液水解酶，并可能通过形成抑制酶复合物限制底物对酶的可用性，或直接结合酶的活性位点影响酶活性，从而减轻毒液引起的毒性。
