Biomolecular investigation into systemic vascular leakage and kidney dysfunction induced by Russell's viper: a unique type of vascular toxicity and pathophysiology in viperid envenomings

Abstract

Envenoming by Daboia russelii (Russell’s viper) is a significant public health concern in Asian and India and is characterized by kidney dysfunction and acute kidney injury (AKI) in addition to the more common effects associated with coagulopathies. Generally, treatment with appropriate antivenom successfully ameliorates both coagulopathy and often AKI. Delayed or lack of treatment often leads to significant pathophysiology requiring hemodialysis putting more burden on patients and health care systems. Our laboratory is investigating the molecular mechanisms of systemic vascular leakage and whether these are connected to kidney dysfunction. Both, phospholipase A2s and snake venom VEGFs have been demonstrated capable to produce vascular leakage. To assess whether this pathology is related to kidney dysfunction we utilized the PLA2 inhibitor varespladip and sv-VEGF anti-body to determine whether these could attenuate vascular permeability and subsequently kidney dysfunction. In the case of varespladip, complete enzymatic inhibition of venom PLA2s did not block vascular leakage or kidney dysfunction. Similarly, anti-svVEGF or anti-human VEGF was unable to completely block kidney dysfunction. Although we cannot fully discount the role of svVEGF in kidney dysfunction given the nature of these experiments the data suggests consideration of other factors that occur during envenoming that may contribute to kidney dysfunction. These will be discussed and are currently under investigation.