Inflammation in cerebral ischemia reperfusion improved by avanafil via nod-like receptor protein-3 inflammasome: an experimental study in rats

Abstract

ABSTRACT Objective The aim of study was to investigate the effect of avanafil, a second-generation phosphodiesterase-5 (PDE5) inhibitor, on cerebral ischemia reperfusion (CI/R) model. Methods 32 male albino Wistar rats were used. Four groups were constituted, as I: the healthy (sham), II: the CI/R group, III: the CI/R +I 10 mg/kg avanafil group, and IV: the CI/R + 20 mg/kg avanafil group. Avanafil was administered twice via oral gavage, first shortly after ischemia reperfusion and once more after 12 h. The rats were euthanized after 24 h. Histopathological and Real Time PCR analyzes were performed on cerebral tissues. Results IL-1β, NLRP3 and TNF-α mRNA expressions were statistically higher in the CI/R group when compared to healthy (sham) group. Conversely, the IL-1β, NLRP3, and TNF-α mRNA expressions were significantly decreased in both of the avanafil-treated groups when compared to CI/R group. Histopathological results showed that both doses of avanafil also decreased cellular damage in cerebral tissue that occurred after CI/R. Conclusion Avanafil, was found to have ameliorated inflammatory response and cellular injury caused by CI/R. The mRNA expression of IL-1β, NLRP3, and TNF-α decreased in the I/R groups and approached the control group levels with a high dose of avanafil.