Molecular mechanism of lung hemorrhage induction by VRV-PL-VIIIa from Russell's viper (Vipera russelli) venom

The basic phospholipase A(2) (VRV-PL-VIIIa) from Vipera russelli venom indu ces multiple toxic effects including neurotoxicity, myotoxicity, edema and hemorrhage. This phospholipase A(2) has been extensively characterized for its pharmacological properties except for hemorrhagic activity. In the pres ent investigation, the lung hemorrhagic activity was assayed using lung dye diffusion method. The investigations to understand the mechanism of lung h emorrhage induction by VRV-PL-VIIIa was followed by chemical modification s tudies and also by interaction with an antihemorrhagic factor p-anisic acid (4-methoxy benzoic acid). In presence of 1:2 mol:mol PLA(2): anisic acid, the lung hemorrhagic and edema inducing activities were completely neutrali zed in experimental animals; however, catalytic and anticoagulant activitie s were not neutralized. Carbamylation of VRV-PL-VIIIa resulted in the loss of lung hemorrhage and edema inducing activities. In contrast, carbamylatio n of VRV-PL-VIIIa in the presence of anisic acid could not neutralize the l ung hemorrhage and edema inducing activities. The anticoagulant and enzyme activities were only partially neutralized when carbamylated both in the pr esence and absence of anisic acid. (C) 2000 Elsevier Science Ltd. All right s reserved.