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

Abstract

The basic phospholipase A(2) (VRV-PL-VIIIa) from Vipera russelli venom induces 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 present investigation, the lung hemorrhagic activity was assayed using lung dye diffusion method. The investigations to understand the mechanism of lung hemorrhage induction by VRV-PL-VIIIa was followed by chemical modification studies 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 neutralized in experimental animals; however, catalytic and anticoagulant activities were not neutralized. Carbamylation of VRV-PL-VIIIa resulted in the loss of lung hemorrhage and edema inducing activities. In contrast, carbamylation of VRV-PL-VIIIa in the presence of anisic acid could not neutralize the lung hemorrhage and edema inducing activities. The anticoagulant and enzyme activities were only partially neutralized when carbamylated both in the presence and absence of anisic acid.

• Authors: B Uma, T Veerabasappa Gowda
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 38 Issue 8 Pg. 1129-47 (Aug 2000) ISSN: 0041-0101 [Print] England
• PMID: 10708803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Hydroxybenzoate Ethers
• Proteins
• Salicylates
• Viper Venoms
• Betaine
• 2-methoxybenzoic acid
• Carbamyl Phosphate
• Phospholipases A
• Group II Phospholipases A2
• VRV-PL-VIIIa phospholipase A2, Vipera russelli

Topics

• Animals
• Anticoagulants (toxicity)
• Betaine (chemistry)
• Carbamyl Phosphate (chemistry)
• Edema (chemically induced, pathology)
• Group II Phospholipases A2
• Hemolysis (drug effects)
• Hemorrhage (chemically induced)
• Hydroxybenzoate Ethers
• Lung Diseases (chemically induced)
• Male
• Mice
• Phospholipases A (chemistry, toxicity)
• Proteins (chemistry)
• Prothrombin Time
• Rats
• Russell's Viper (metabolism)
• Salicylates
• Spectrometry, Fluorescence
• Viper Venoms (chemistry, enzymology, toxicity)