Effect of curcumin on methotrexate-induced ovarian damage and follicle reserve in rats: the role of PARP-1 and P53

Methotrexate (MTX) is an agent used in the treatment of many neoplastic and non-neoplastic diseases and is known to cause oxidative damage in normal tissues. Curcumin (Cur) is a natural polyphenol compound with powerful antioxidant and antiapoptotic effects. In this study we investigate the effects of Cur on MTX-induced ovarian damage. Thirty-two young adult female Wistar albino rats were divided into four groups: (1) Control (<i>n</i> = 8): only vehicle group, (2) Cur (<i>n</i> = 8): Cur-only group (200 mg/kg/day), (3) MTX (<i>n</i> = 8): MTX-only group (0.35 mg/kg/day), (4) MTX+Cur (<i>n</i> = 8): The group was given MTX (0.35 mg/kg/day) and Cur (200 mg/kg/day) for 28 days. Then, SOD, CAT, MDA, AMH levels were measured using ELISA kits. Follicle count was performed on H&amp;E stained slides. In addition, the expressions of P53 and PARP-1 were analysed by immunohistochemistry. MDA levels were seen to be higher in the MTX group than in the MTX+Cur group (<i>p</i> &lt; 0.05). Cur treatment lowered MDA levels and increased SOD and CAT levels (<i>p</i> &lt; 0.05 for all). In the MTX+Cur group, atretic follicle count decreased (<i>p</i> &lt; 0,05), however, primordial follicle count increased (<i>p</i> &lt; 0,01). Secondary follicle count and AMH levels were higher in MTX-treated groups (<i>p</i> &lt; 0,05 and <i>p</i> &lt; 0,01, respectively). Expressions of p53 and Poly [ADP-ribose] polymerase 1 (PARP-1) increased significantly in the MTX group compared to the other groups (<i>p</i> &lt; 0,05). Cur pretreatment prior to MTX administration may be an effective option in preserving the ovarian follicle pool by regulating P53 and PARP-1 expressions with its antioxidant effect. MTX has a negative effect on ovarian follicle reserve in ratsCurcumin, with its antioxidant activity, prevents MTX-induced follicle loss through the p53 and PARP-1 mediated pathway.In the MTX ovarian follicle reserve model in rats, AMH may be insufficient to reflect follicle reserve. MTX has a negative effect on ovarian follicle reserve in rats Curcumin, with its antioxidant activity, prevents MTX-induced follicle loss through the p53 and PARP-1 mediated pathway. In the MTX ovarian follicle reserve model in rats, AMH may be insufficient to reflect follicle reserve.