Resveratrol inhibits inflammatory signaling implicated in ionizing radiation-induced premature ovarian failure through antagonistic crosstalk between silencing information regulator 1 (SIRTI) and poly (ADP-ribose) polymerase 1 (PARP-1)

This study hypothesized that resveratrol, a silencing information regulator 1 (SIRT1) activator, would counteract the inflammatory signaling associated with radiotherapy-induced premature ovarian failure (POP). Immature female Sprague-Dawley rats were subjected to a single dose of gamma-radiation to. induce POF and treated with resveratrol (25 mg/kg) once daily for two weeks before and three days post irradiation. Resveratrol preserves the entire ovarian follicle pool manifested by increasing serum anti-Mullerian hormone (AMH) levels. Radiation triggered inflammatory process in the ovary through enhanced NF-kappa B and poly(ADP-ribose) polymerase (PARP)-1 expression which convinced the expression of inflammatory markers including IL-6, IL-8, and visfatin mRNA levels, as well as inducible nitric oxide synthase and cyclooxygenase-2 protein expression with a concomitant reduction in IL-10 mRNA levels. Resveratrol significantly counteracted the effect of radiation and upregulated the gene expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and SIRT1. Resveratrol-activated SIRT1 expression was associated with inhibition of PARP-1 and NF-kappa B expression-mediated inflammatory cytokines. Our findings suggest that resveratrol restored ovarian function through increasing AMH levels, and diminishing ovarian inflammation, predominantly via upregulation of PPAR-gamma and SIRT1 expression leading to inhibition of NF-kappa B provoked inflammatory cytokines. (C) 2016 Elsevier Inc. All rights reserved.