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Biochem Pharmacol. 2016 Mar 1;103:140-50. doi: 10.1016/j.bcp.2016.01.019. Epub 2016 Jan 28.

Resveratrol inhibits inflammatory signaling implicated in ionizing radiation-induced premature ovarian failure through antagonistic crosstalk between silencing information regulator 1 (SIRT1) and poly(ADP-ribose) polymerase 1 (PARP-1).

Author information

1
National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
2
Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Electronic address: ebtehal_dm@yahoo.com.
3
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

Abstract

This study hypothesized that resveratrol, a silencing information regulator 1 (SIRT1) activator, would counteract the inflammatory signaling associated with radiotherapy-induced premature ovarian failure (POF). Immature female Sprague-Dawley rats were subjected to a single dose of γ-radiation to induce POF and treated with resveratrol (25mg/kg) once daily for two weeks before and three days post irradiation. Resveratrol preserves the entire ovarian follicle pool manifested by increasing serum anti-Müllerian hormone (AMH) levels. Radiation triggered inflammatory process in the ovary through enhanced NF-κB 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 γ (PPAR-γ) and SIRT1. Resveratrol-activated SIRT1 expression was associated with inhibition of PARP-1 and NF-κB 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-γ and SIRT1 expression leading to inhibition of NF-κB provoked inflammatory cytokines.

KEYWORDS:

Inflammation; Ovarian failure; Resveratrol; SIRT1; γ-Radiation

PMID:
26827941
DOI:
10.1016/j.bcp.2016.01.019
[Indexed for MEDLINE]

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