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

Abstract

Background: 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.

Materials and methods: Thirty-two young adult female Wistar albino rats were divided into four groups: (1) Control (n = 8): only vehicle group, (2) Cur (n = 8): Cur-only group (200 mg/kg/day), (3) MTX (n = 8): MTX-only group (0.35 mg/kg/day), (4) MTX+Cur (n = 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&E stained slides. In addition, the expressions of P53 and PARP-1 were analysed by immunohistochemistry.

Results: MDA levels were seen to be higher in the MTX group than in the MTX+Cur group (p < 0.05). Cur treatment lowered MDA levels and increased SOD and CAT levels (p < 0.05 for all). In the MTX+Cur group, atretic follicle count decreased (p < 0,05), however, primordial follicle count increased (p < 0,01). Secondary follicle count and AMH levels were higher in MTX-treated groups (p < 0,05 and p < 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 (p < 0,05).

Conclusion: 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.