Erisgin Zuleyha, Mutlu Hasan Serdar, Turkoglu İsmail, Cinar Esma, Barak M Zuhal, Aydin Ismail, Usta Murat, Tekelioglu Yavuz
Department of Histology and Embryology, Faculty of Medicine, Giresun University, Giresun, Türkiye.
Department of Pathology, Faculty of Medicine, Giresun University, Giresun, Türkiye.
J Mol Histol. 2025 Aug 29;56(5):288. doi: 10.1007/s10735-025-10566-5.
Methotrexate (MTX) is still a broad-spectrum drug that has been used for almost a century for leukemia, rheumatoid arthritis, ectopic pregnancy. This study investigates the protective effects of coenzyme Q10 (CoQ10) on MTX induced gonadotoxicity. Twenty-four female wistar albino rats were divided into four groups. Control group; 1 ml corn oil was applied by oral gavage (p.o.). CoQ10 group; 100 mg/kg CoQ10 (in 1 ml corn oil) was applied by p.o. for seven days. MTX group; 20 mg/kg MTX intraperitoneal (i.p.) was used one time on the first day of the experiment. MTX + CoQ10 group; 20 mg/kg MTX i.p. one time and 100 mg/kg CoQ10 (in 1 ml corn oil) was applied p.o. for seven days. At the end of the experiment, all animals were euthanized under anesthesia, and blood samples were taken from intracardiac. The both sides ovaries were taken out and were put in to neutral formalin. Biochemical analysis for serum anti-mullerian hormone (AMH), flow cytometry for apoptosis (Annexin V), and histopathologic analysis with follicle counting were performed in ovarian tissues. According to results of follicle counting, apoptosis, morphometric and AMH analysis; there was no statistically significant difference in terms of follicle numbers and ovarium diameter between all groups. However, apoptosis significantly increased in the MTX group and decreased in the MTX + CoQ10 group. AMH level was decreased in the MTX group and interestingly significantly increased in the only CoQ10 treatment group and. As a result, CoQ10 has protective effects in terms of apoptosis and AMH against MTX induced gonadotoxicity.
甲氨蝶呤(MTX)仍然是一种广谱药物,近一个世纪以来一直用于治疗白血病、类风湿性关节炎和异位妊娠。本研究调查辅酶Q10(CoQ10)对MTX诱导的性腺毒性的保护作用。将24只雌性Wistar白化大鼠分为四组。对照组;通过口服灌胃(p.o.)给予1毫升玉米油。CoQ10组;以100毫克/千克CoQ10(溶于1毫升玉米油中)经口服给药7天。MTX组;在实验第一天腹腔注射(i.p.)20毫克/千克MTX一次。MTX + CoQ10组;腹腔注射20毫克/千克MTX一次,并以100毫克/千克CoQ10(溶于1毫升玉米油中)经口服给药7天。实验结束时,所有动物在麻醉下安乐死,从心脏采集血样。取出双侧卵巢并放入中性福尔马林中。对卵巢组织进行血清抗苗勒管激素(AMH)的生化分析、凋亡(膜联蛋白V)的流式细胞术分析以及卵泡计数的组织病理学分析。根据卵泡计数、凋亡、形态计量学和AMH分析结果;所有组之间在卵泡数量和卵巢直径方面无统计学显著差异。然而,MTX组凋亡显著增加,而MTX + CoQ10组凋亡减少。MTX组AMH水平降低,有趣的是,仅CoQ10治疗组AMH水平显著升高。结果,CoQ10在凋亡和AMH方面对MTX诱导的性腺毒性具有保护作用。