Myotoxicity and physiological effects of three Trimeresurus flavoviridis phospholipases A2

When basic proteins I and II from Trimeresurus flavoviridis (Habu snake) venom, which are Lys-49-phospholipase A2 (PLA2) with low activity, were injected intramuscularly into mice, myonecrosis was induced accompanied by a rapid increase of plasma creatine kinase level. This increase was about 2 times greater than that raised by highly active T. flavoviridis Asp-49-PLA2 which has been regarded as a myotoxic factor. Calcium-dependent depolarization of frog muscle fibers was observed with basic proteins I and II but not with Asp-49-PLA2. Indirect hemolysis of rat erythrocytes was induced by Asp-49-PLA2 but not by basic proteins I and II. Myotoxicity and depolarization effects appear to be not necessarily related to lipolytic activity of proteins although hemolytic effects is in parallel to lipolytic potency. Light microscopic observations of muscle preparations treated with three PLA2s showed similar histological changes, i.e., myolytic necrosis without hemorrhage and infiltration of polymorphonuclear cells. The structural and functional elements of PLA2s for eliciting myotoxicity are discussed.