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

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.

KEYWORDS:

• Avanafil
• phosphodiesterase-5 inhibitor
• ischemia reperfusion
• NLRP3
• rat

Acknowledgments

We would like to thank Prof. Dr. Zekai Halıcı for his scientific contributions.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

All of the authors equally participated in the design, interpretation of the studies, analysis of the data, and review of the manuscript.

Ethical approval

The ethical committee approval was obtained from the Local Animal Care Committee of Ataturk University with the decision number of 2,000,273,288 on November 3rd, 2020.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.