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Multiple dose treatment reduces cyclophosphamide-induced ovarian follicular loss in mice.
Birth Defects Research ( IF 2.1 ) Pub Date : 2019-10-23 , DOI: 10.1002/bdr2.1603
Vadakkepurath Raj Athira 1 , Madathiparambil Karthikeyan Saranya 1 , Thimmappa Shivanandappa 1 , Hanumant Narasinhacharya Yajurvedi 1
Affiliation  

This study compares the effects of single dose and multiple dose treatment of cyclophosphamide (CP) on oxidative stress‐mediated follicular damage in mouse ovary. In the first experiment, adult female mice were administered with a single dose of CP (100 mg/kg body weight/mouse) and autopsied 72 hr after treatment. In the second experiment, adult female mice were injected with multiple doses of CP (40 mg/kg body weight/day/mouse for 10 consecutive days) and sacrificed on Day 11. There was a 58, 48, 53, and 51% loss of primordial, primary, preantral, and antral follicles, respectively, following the administration of a single dose of CP, whereas, multiple dose of CP caused only 35% reduction in primordial follicles coupled with 28, 23, and 38%, loss of primary, preantral, and antral follicles, respectively. There was a decrease in activities of the ovarian antioxidant enzymes and increase in reactive oxygen species (ROS) and malondialdehyde (MDA) concentrations following single dose CP, whereas multiple dose treatment caused an increase in activities of these enzymes and decrease in ROS and MDA concentrations. The serum concentration of estradiol was significantly decreased following single or multiple dose treatment. The ovarian damage caused by a single high dose of CP administration is higher than that by multiple doses of smaller amount, though the total amount of CP administered was higher with multiple treatment. The results of the current study reveal the benefit of metronomic chemotherapy in cancer treatment, for its effectiveness in reducing ovarian toxicity, a major side effect in young female patients.

中文翻译:

多剂量治疗可减少环磷酰胺诱发的小鼠卵巢滤泡损失。

这项研究比较了单剂量和多剂量环磷酰胺(CP)对小鼠卵巢氧化应激介导的滤泡损伤的影响。在第一个实验中,给成年雌性小鼠单剂量的CP(100 mg / kg体重/小鼠),并在治疗后72小时进行尸检。在第二个实验中,给成年雌性小鼠注射多剂量的CP(连续10天每天注射40 mg / kg体重/天/小鼠)并在第11天处死。损失58%,48%,53%和51%单一剂量的CP后,原代,原发,窦前和肛门窦卵泡的数量分别减少,而多剂量的CP仅使原代卵泡减少35%,再加上28%,23%和38%的原发性卵泡减少,窦前卵泡和肛门卵泡。单剂量CP后卵巢抗氧化酶活性下降,活性氧(ROS)和丙二醛(MDA)浓度增加,而多剂量治疗导致这些酶活性增加,ROS和MDA浓度降低。单次或多次剂量治疗后,雌二醇的血清浓度显着降低。尽管多次治疗CP的总剂量更高,但一次高剂量CP的给药对卵巢的损害要高于多次小剂量的卵巢。目前的研究结果表明,节律化学疗法可有效降低癌症的卵巢毒性,这是年轻女性患者的主要副作用,它可有效治疗癌症。
更新日期:2019-10-23
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