Phospholipase A₂ inhibitor varespladib prevents wasp sting-induced nephrotoxicity in rats

This study aimed to clarify whether varespladib, a phospholipase A₂ (PLA₂) inhibitor, can be used as a therapeutic agent for wasp sting-induced acute kidney injury (AKI). Rats were divided into control, AKI, and AKI + varespladib groups. The AKI model was established by subcutaneously injecting wasp venom at five different sites in rats. Varespladib treatment showed a significant inhibitory effect on wasp venom PLA₂in vitro and in vivo. Moreover, we observed that varespladib decreased the levels of rhabdomyolysis and hemolysis markers compared with that in the AKI group. Histopathological changes in the kidney decreased significantly, and rat serum creatinine levels were reduced after varespladib administration. The significantly regulated genes in the kidney of the AKI group were mostly involved in inflammatory response pathway, and the administration of varespladib remarkably attenuated the expression of these genes. Therefore, varespladib inhibited wasp sting-induced functional and pathological damage to the kidneys. We propose that the PLA₂ inhibitor varespladib protects the kidney tissue in a wasp sting-induced AKI model by inhibiting PLA₂ activity.