Keçeci Mete, Karaoluk Nesibe
Department of Histology and Embryology, Bülent Ecevit University, Zonguldak, Turkey.
Ann Med. 2025 Dec;57(1):2446688. doi: 10.1080/07853890.2024.2446688. Epub 2024 Dec 27.
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 ( = 8): only vehicle group, (2) Cur ( = 8): Cur-only group (200 mg/kg/day), (3) MTX ( = 8): MTX-only group (0.35 mg/kg/day), (4) MTX+Cur ( = 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.
MDA levels were seen to be higher in the MTX group than in the MTX+Cur group ( < 0.05). Cur treatment lowered MDA levels and increased SOD and CAT levels ( < 0.05 for all). In the MTX+Cur group, atretic follicle count decreased ( < 0,05), however, primordial follicle count increased ( < 0,01). Secondary follicle count and AMH levels were higher in MTX-treated groups ( < 0,05 and < 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 ( < 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.
甲氨蝶呤（MTX）是一种用于治疗多种肿瘤性和非肿瘤性疾病的药物，已知会对正常组织造成氧化损伤。姜黄素（Cur）是一种具有强大抗氧化和抗凋亡作用的天然多酚化合物。在本研究中，我们探究了姜黄素对甲氨蝶呤诱导的卵巢损伤的影响。
将32只年轻成年雌性Wistar白化大鼠分为四组：（1）对照组（n = 8）：仅给予赋形剂组；（2）姜黄素组（n = 8）：仅给予姜黄素组（200mg/kg/天）；（3）甲氨蝶呤组（n = 8）：仅给予甲氨蝶呤组（0.35mg/kg/天）；（4）甲氨蝶呤+姜黄素组（n = 8）：该组给予甲氨蝶呤（0.35mg/kg/天）和姜黄素（200mg/kg/天），持续28天。然后，使用酶联免疫吸附测定试剂盒测量超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、丙二醛（MDA）、抗缪勒管激素（AMH）水平。在苏木精-伊红（H&E）染色的载玻片上进行卵泡计数。此外，通过免疫组织化学分析P53和聚[ADP-核糖]聚合酶-1（PARP-1）的表达。
甲氨蝶呤组的MDA水平高于甲氨蝶呤+姜黄素组（P < 0.05）。姜黄素治疗降低了MDA水平，提高了SOD和CAT水平（均P < 0.05）。在甲氨蝶呤+姜黄素组中，闭锁卵泡计数减少（P < 0.05），然而，原始卵泡计数增加（P < 0.01）。甲氨蝶呤治疗组的次级卵泡计数和AMH水平较高（分别为P < 0.05和P < 0.01）。与其他组相比，甲氨蝶呤组中p53和聚[ADP-核糖]聚合酶1（PARP-1）的表达显著增加（P < 0.05）。
在给予甲氨蝶呤之前进行姜黄素预处理，可能通过其抗氧化作用调节P53和PARP-与PARP-1的表达，从而成为保护卵巢卵泡池的有效选择。 1的表达，从而成为保护卵巢卵泡池的有效选择。
