Thrombolytic Effects of Philippine Pit Viper (Trimeresurus flavomaculatus) Venom in Human Blood In Vitro and Ferric Chloride-Induced Cardiac Thrombosis on Swiss Webster Mice In Vivo.

Abstract

Thrombosis is one of the leading causes of mortality worldwide. Thrombolytic agents are used to reduce this burden. Studies pointed out that certain proteins in the venom of several snake species may have potential thrombolytic properties.Trimeresurus flavomaculatus, known as the Philippine pit viper, is found along damp localities in the Philippines. Venoms of closely related specieshave been shown to exhibit thrombolytic effectsin vitroandin vivo. However, no extensive studies yet have been conducted about the thrombolytic effect ofT. flavomaculatusvenom.Thus, this two-phased study aimed to determine the thrombolytic effect ofT. flavomaculatusvenom on human blood and ferric chloride-inducedcardiac thrombosis in mice. Phase 1 was done using clot lysis method to measure thrombolytic activityin vitro. Venom dilutions of 3:4, 1:2, 2:3, and 1:0, positive control (streptokinase), and negative control (normal saline solution) were inoculated to different samples of human blood. Phase 2 measured the thrombolytic activityin vivo. Ferric chloride-saturatedfilter paper was applied over the cardiac wall for the induction of thrombus formation. Venom dilutions of 1:64, 1:16, 1:4, and 1:1, positive control (streptokinase), and negative control (normal saline solution) were then injected through the dorsal tail vein of mice. After 1 hour, the cardiac tissues were excised for histologic examination. Phase 1 results showed that the venom had significant thrombolytic activityin vitro. Dilutions of 1:0 and 3:4 had no significant differences with streptokinasein vitro. Phase 2 results showed significant lysisin vivoat 1:1, 1:4, and 1:64 venom dilutions. The results indicated thatT. flavomaculatushas a potential thrombolytic activity bothin vitroandin vivo.