Ação protetora do varespladib (LY-315929) isolado ou associado ao antiveneno sobre os efeitos locais e sistemicos induzidos pelo veneno de Lachesis muta rhombeata (Surucucu Sul-Americana) em rato

Abstract

In recent years, several studies have reported the efficacy of varespladib (VPL) as a potential antivenom agent against snake venoms dependent on phospholipase A2, present in the Viperidae and Elapidae groups. The objective was to evaluate the action of varespladib (phospholipase A2 inhibitor) associated or not with antivenom on local and systemic alterations induced by the venom of Lachesis muta rhombeata (Surucucu Sul-Americana) in rats. Methodology: Male Wistar rats (250-300 g) were divided into five groups with six animals each: G1-control; G2-Lmr venom (1500 µg/kg); G3-Lmr poison/antivenom; G4-venom Lmr/VPL; G5-venom Lmr/antivenom/. Animals were monitored for 120 minutes after venom injection, followed by anesthesia and euthanasia to collect blood samples for hemogram, biochemical analysis of alanine aminotransferase (ALT), creatinine, urea, creatine kinase (CK), alkaline phosphatase (FA), and lactate dehydrogenase (LDH), and histology of the injected gastrocnemius muscle and its contralateral liver, lung, heart, kidney. Results: the venom caused local and systemic damage; there was no significant change in blood count, ALT, FA and creatinine; there was a significant increase (P<0.05) in LDH and urea which was reduced in all treated groups; in G4 and G5, a protective effect of NPV and the synergism of associated treatments (ATV/NPV) was observed. G2 showed significant inflammatory neutrophilic infiltrate and diffuse necrosis, and in the other treated groups, attenuation of these changes was observed, with difference in relation to G2 (P<0.05). a reduction in the lesion score was observed in relation to G2. In G5, the lesion score did not differ from the control, showing the effectiveness of the associated treatments. Conclusion: In conclusion, L. muta rhombeata venom induced significant local and systemic tissue damage in rats 2 hours after its injection, with VPL combined with antivenom there was greater efficiency in preventing this change. Experimental poisoning induced systemic changes that were more pronounced by increasing LDH and urea, with only the latter being prevented by VPL alone or combined with antivenom.