title: 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).
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.
authors.affiliation: National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
authors.forename: Riham Soliman
authors.initials: RS
authors.lastname: Said
authors.affiliation: Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Electronic address: ebtehal_dm@yahoo.com.
authors.forename: Ebtehal
authors.initials: E
authors.lastname: El-Demerdash
authors.affiliation: National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
authors.forename: Ahmed Shafik
authors.initials: AS
authors.lastname: Nada
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Kamal
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005720:Gamma Rays; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology; D065851:Ovarian Reserve / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D016649:Primary Ovarian Insufficiency / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D047495:PPAR gamma; D013267:Stilbenes; D051996:Transcription Factor RelA; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Inflammation; Ovarian failure; Resveratrol; SIRT1; γ-Radiation