Almasi Majid, Shafiei Golnaz, Nikzad Hossein, Karimian Mohammad, Moshkdanian Ghazaleh
Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
Int J Reprod Biomed. 2024 Oct 14;22(8):661-672. doi: 10.18502/ijrm.v22i8.17262. eCollection 2024 Aug.
Cyclophosphamide (CP), a utilized anticancer drug, is known to cause infertility in women. However, L-carnitine (LC), an antioxidant, has been shown to offer protective benefits against infertility.
This study aimed to evaluate the levels of reactive oxygen species (ROS) and apoptotic gene expression in mice treated with CP and LC.
24 NMRI female mice (6-8 wk, 30 5 gr) were divided into 4 groups: control group: received normal saline intraperitoneal (IP) injection for 10 days; CP group: received 75 mg/kg of CP as a single IP on the 10 day of the experiment; LC group: received 200 mg/kg of LC IP for 10 days; LC+CP group: received LC for 10 days and CP single IP injection on the 10 day of the experiment. After 10 days, mice were superovulated. The oviducts were then removed, and the oocytes of each group were collected for evaluating apoptotic gene expression B-cell lymphoma 2(), -associated X(), and via real-time polymerase chain reaction and intracellular ROS levels by dichloro-dihydro-fluorescein diacetate fluorescence staining.
Data revealed that LC in the LC+CP group significantly increased gene expression (p = 0.01), and decreased and gene expression compared to the CP group (p = 0.03, p = 0.04). LC decreased the ROS level in the LC+CP group compared to the CP group (p 0.001).
Findings suggest that LC can scavenge the ROS caused by CP and modulate the apoptotic pathway via downregulating the and genes and upregulating the gene in oocytes of mice exposed to CP.
环磷酰胺（CP）是一种常用的抗癌药物，已知会导致女性不孕。然而，左旋肉碱（LC）作为一种抗氧化剂，已被证明对不孕具有保护作用。
本研究旨在评估用CP和LC处理的小鼠体内活性氧（ROS）水平和凋亡基因表达情况。
将24只NMRI雌性小鼠（6 - 8周龄，体重30±5克）分为4组：对照组：腹腔注射生理盐水10天；CP组：在实验第10天腹腔注射75毫克/千克CP一次；LC组：腹腔注射200毫克/千克LC，持续10天；LC + CP组：先腹腔注射LC 10天，在实验第10天腹腔注射一次CP。10天后，对小鼠进行超排卵处理。然后取出输卵管，收集每组的卵母细胞，通过实时聚合酶链反应评估凋亡基因B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）和半胱天冬酶3（Caspase-3）的表达，并通过二氯二氢荧光素二乙酸酯荧光染色评估细胞内ROS水平。
数据显示，与CP组相比，LC + CP组中的LC显著增加了Bcl-2基因表达（p = 0.01），并降低了Bax和Caspase-3基因表达（p = 0.03，p = 0.04）。与CP组相比，LC降低了LC + CP组中的ROS水平（p < 0.001）。
研究结果表明，LC可以清除CP产生的ROS，并通过下调暴露于CP的小鼠卵母细胞中的Bax和Caspase-3基因以及上调Bcl-2基因来调节凋亡途径。
