左旋肉碱改善甲氨蝶呤诱导的雌性大鼠卵巢功能障碍

Hala I. Madkour, Safia B. Ahmed, W. Mohammed
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摘要

本研究旨在探讨补充左旋肉碱(L-car)对甲氨蝶呤(MTX)相关卵巢功能障碍的影响。体重200 ~ 250 g的雌性白化大鼠50只,随机分为5组,每组10只;实验时间为四周。对照组给予生理盐水(IP)。MTX组给予1 mg/kg (IP),每周1次,连用4周。MTX+L-car50、MTX+L-car100和MTX+叶酸组:每天分别口服L-car(50或100 mg/kg)或叶酸250µg/kg(口服)加1 mg/kg甲氨蝶呤(IP),每周1次,持续4周。MTX组大鼠体重、卵巢重量、卵巢指数、血清总抗氧化能力(TAC)和血清抗勒氏杆菌激素(AMH)均显著降低。血清总氧化状态(TOS)、氧化应激指数(OSI)、卵巢组织丙二醛(MDA)、一氧化氮(NO)和caspase-3水平均显著升高。卵巢组织有组织学异常,腔内卵泡计数(AFC)明显增高。给予L-car(50或100 mg/kg)或叶酸可纠正异常生化参数,改善组织病理异常和AFC。提示L-car可能通过抗氧化、抗细胞凋亡和改善卵巢储备等作用,对mtx诱导的雌性大鼠卵巢功能障碍具有保护作用。
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L-carnitine ameliorates methotrexate-induced ovarian dysfunction in female rats
This study aimed to investigate the effect of L-carnitine (L-car) supplementation on methotrexate (MTX) related ovarian dysfunction. Fifty female albino rats weighing 200 –250 g were randomly divided into five groups (10 rats each); the duration of the experiment was four weeks. Control group received saline (IP). MTX group received 1 mg/kg (IP) once weekly for four weeks. Whereas, MTX+L-car50, MTX+L-car100 and MTX+folic acid groups: daily received either L-car (50 or 100 mg/kg) or folic acid 250 µg/kg respectively (orally) plus 1 mg/kg methotrexate (IP) once weekly for four weeks. Treatment of the rats with MTX produced a significant decrease in body and ovarian weights, ovarian index, serum total antioxidant capacity (TAC) and serum anti-Müllerian hormone (AMH). However, serum total oxidant status (TOS), Oxidative stress index (OSI), ovarian tissue malondialdehyde (MDA), nitric oxide (NO) and caspase-3 levels were significantly increased. Besides, there were histological abnormalities in the ovarian tissues with a significant increase in antral follicles count (AFC). Administration of either L-car (50 or 100 mg/kg) or folic acid corrected the abnormal biochemical parameters and improved the histopathological abnormalities and AFC. These data suggested that L-car might protect against MTX-induced ovarian dysfunction in female rats through antioxidant, anti-apoptotic effects and improving the ovarian reserve.
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