Physiology Monitoring as a Tool of Effective Venom Research

Abstract

The commercial availability of the snake venom antiserum (SVA) significantly improved the chances of survival of snakebite victims and eventually, the research on phytotherapeutics for snake envenomation declined. India is the capital of snakebite deaths and needs safer molecules for treatment. Systematic investigations on phytotherapeutics are carried out on many animals, and most of them are sacrificed. The study evaluates the possibility of reducing the number of animals sacrificed in venom research by monitoring physiological parameters. Respiratory and electrocardiographic (ECG) monitoring was done in anaesthetized rats after administration of Naja naja (neurotoxic) and Daboia russelii (cytotoxic) venoms separately. Anti-venom action of Woodfordia fruticosa (Lythraceae) extract was evaluated against these venoms and SVA was used as the positive control. Physiological parameters were recorded with the LabChart® program and PowerLab® system coupled with 3 electrode ECG bioamplifier and a respiratory flow-head with a custom-designed mask. Sinus bradycardia was a major cardiac effect imparted by both venoms. The absence or inverted appearance of P-waves, PR prolongation, changes in QRS configuration and QT prolongation were induced by venoms. Significant respiratory depression was observed with N. najavenom and significant ECG changes were observed with D. russelii venom. W. fruticosa extract significantly prevented envenomed animals from developing sinus bradycardia (P < 0.001) for both venoms comparable to the action of SVA. W. fruticosa extract reversed severe respiratory depression induced by N. naja venom up to 70% and D. russelii venom up to 91%. Prolongation of PR and QT intervals induced by both the venoms was significantly reversed by W. fruticosa extract (p < 0.001). Development of RSR’ configuration in ECG and changes to cardiac axis induced by D. russelii venom were reversed by W. fruticosa. Possible mechanisms of venom toxicity and their reversal can be studied with such well-designed methods, and using sub-lethal venom doses would reduce animal sacrifices. Correlating prospective clinical case studies of snakebite victims with these controlled animal studies can generate base data for future venom research.