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孕期前化疗暴露对胎儿脑组织的影响及槲皮素的潜在保护作用。

Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin.

作者信息

Doğan Z, Kocahan S, Erdemli E, Köse E, Yılmaz I, Ekincioğlu Z, Ekinci N, Turkoz Y

机构信息

Department of Anatomy, Faculty of Medicine, Adiyaman University, 02040, Adiyaman, Turkey.

Department of Physiology, Faculty of Medicine, Adiyaman University, 02040, Adiyaman, Turkey.

出版信息

Cytotechnology. 2015 Dec;67(6):1031-8. doi: 10.1007/s10616-014-9742-z. Epub 2014 Sep 27.

Abstract

Cyclophosphamide (CYC) and doxorubicin (DOX) are among the most effective and widely used anticancer chemotherapeutic drugs. Potential chemopreventive and chemotherapeutic functions have recently been attributed to flavonoids. We hypothesized that Quercetin (QR) would protect against the toxic effects of chemotherapeutic agents applied prior to pregnancy. Rats were treated with the chemotherapeutic drugs CYC (27 mg/kg) and DOX (1.8 mg/kg) applied in a single intraperitoneal dose once every 3 weeks for 10 weeks. QR was administered at a dose of 10 mg/kg/day by oral gavage. 48 h following the experimental chemotherapy exposure, female rats were transferred to cages containing male rat for mating. Fetal brain tissues were removed from fetuses extracted by cesarean section on the 20th day of gestation for evaluation of antioxidant parameters. A significant increase in superoxide dismutase and malondialdehyde activity was observed in CYC and DOX treatment groups relative to the control group (p < 0.05). Similarly, carnitine acylcarnitine translocase and Glutathione activity was significantly reduced in the CYC and DOX groups relative to the control group (p < 0.05). Our results indicate that the use of chemotherapeutic drugs before pregnancy can result in oxidative damage to fetal brain tissue. Therefore, women who have been exposed to chemotherapy and may become pregnant should be treated with antioxidant compounds such as QR to reduce the risk of damage to fetal brain tissues.

摘要

环磷酰胺(CYC)和阿霉素(DOX)是最有效且应用最广泛的抗癌化疗药物。近年来,黄酮类化合物被认为具有潜在的化学预防和化疗功能。我们推测槲皮素(QR)可以预防孕期前应用化疗药物所产生的毒性作用。大鼠每3周接受一次腹腔注射,单剂量给予化疗药物CYC(27毫克/千克)和DOX(1.8毫克/千克),共给药10周。通过口服灌胃给予大鼠剂量为10毫克/千克/天的QR。在实验性化疗暴露48小时后,将雌性大鼠转移至装有雄性大鼠的笼子中进行交配。在妊娠第20天通过剖宫产取出胎儿,取其脑组织用于评估抗氧化参数。与对照组相比,CYC和DOX治疗组的超氧化物歧化酶和丙二醛活性显著增加(p<0.05)。同样,与对照组相比,CYC和DOX组的肉碱/脂酰肉碱转位酶和谷胱甘肽活性显著降低(p<0.05)。我们的结果表明,孕期前使用化疗药物可导致胎儿脑组织发生氧化损伤。因此,接触过化疗且可能怀孕的女性应使用QR等抗氧化化合物进行治疗,以降低胎儿脑组织受损的风险。

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