Faculty of Medicine, Department of Obstetrics and Gynecology, University of Kuwait, Safat, Kuwait.
Gynecol Endocrinol. 2009 Dec;25(12):816-22. doi: 10.3109/09513590903056811.
Folate antagonists are widely used in the treatment of various cancerous states. Paucity of data on effect of administration of one such widely used drug, methotrexate (MTX), on the status of essential trace elements and antioxidant enzymes in pregnant women or in pregnant animals prompted us to undertake this study.
MTX at a concentration of 5 mg/kg body weight was administered intraperitoneally as single dose to pregnant Sprague-Dawley rats for three consequitive days from day 17 of pregnancy. Control group of pregnant rats received single dose of saline instead of the anti-cancer drug on all the 3 days. After receiving the third dose of drug, the treated rats and control group rats were sacrificed, 1 h after intraperitoneal injection of a cocktail of essential trace elements namely, Cu, Se and Zn administered as a single bolus dose. Blood samples were collected 30 min of trace element cocktail injection, after decapitation and concentrations of trace elements in serum samples were determined by atomic absorption spectrophotometry. Concentrations of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and total antioxidant status were determined by specific analytical kits, using spectrophotometry.
In control group(n = 6), serum concentrations of Cu, Se and Zn averaged 2330.5, 614.8 and 2773.2 microg/l, while in study group (n = 6) the concentrations of trace elements averaged 2294, 596 and 2713 microg/l, respectively. Student's t-test did not show any statistical significance (p > 0.05) between various trace element concentrations in control and treated groups. Cu:Zn ratios of control and treated group of rats did not vary significantly as well. Concentrations of superoxide dismutase, glutathione peroxidase in whole blood samples in control rats averaged 165 and 43,260 U/ml, respectively, while in MTX-treated group of animals the corresponding antioxidant enzymes averaged 330.6 and 67,101 U/ml respectively. SOD and GPX values were significantly higher in drug-treated animals compared to controls (Student's t-test, p < 0.05) However, total antioxidant activity was shown to be significantly lower (Student's t-test; p < 0.05) in the drug-treated group compared to control.
We report for the first time that effect of MTX administration in pregnancy is not associated with significant alteration in disposition of essential trace elements. However, the effect of drug administration on antioxidant enzyme status in pregnant women cannot be excluded while using the drug in clinical states.
叶酸拮抗剂广泛用于治疗各种癌症。由于缺乏关于一种广泛使用的药物甲氨蝶呤（MTX）给药对孕妇或怀孕动物基本微量元素和抗氧化酶状态的影响的数据，我们进行了这项研究。
从妊娠第 17 天开始，连续 3 天，每天给妊娠 Sprague-Dawley 大鼠腹腔内注射 5mg/kg 体重的 MTX 作为单剂量。对照组妊娠大鼠在所有 3 天内给予生理盐水而不是抗癌药物。在接受第三次药物剂量后，在腹腔内注射必需微量元素混合物（即铜、硒和锌）后 1 小时处死接受药物治疗的大鼠和对照组大鼠。用原子吸收分光光度法测定血清样品中的微量元素浓度。用分光光度法，用特定的分析试剂盒测定超氧化物歧化酶、谷胱甘肽过氧化物酶和总抗氧化状态等抗氧化酶的浓度。
在对照组（n=6）中，血清铜、硒和锌的浓度平均为 2330.5、614.8 和 2773.2μg/l，而在研究组（n=6）中，微量元素的浓度平均为 2294、596 和 2713μg/l，分别为。学生 t 检验显示对照组和治疗组之间各种微量元素浓度无统计学意义（p>0.05）。Cu：Zn 比值在对照组和治疗组大鼠中也没有显著差异。对照组大鼠全血样本中超氧化物歧化酶、谷胱甘肽过氧化物酶的浓度平均为 165 和 43260U/ml，而 MTX 处理组动物相应的抗氧化酶平均为 330.6 和 67101U/ml。与对照组相比，药物处理组动物的 SOD 和 GPX 值显著升高（学生 t 检验，p<0.05）。然而，与对照组相比，药物处理组的总抗氧化活性显著降低（学生 t 检验；p<0.05）。
我们首次报道，MTX 给药在妊娠期间的作用与必需微量元素分布的显著改变无关。然而，在临床状态下使用该药物时，不能排除药物给药对孕妇抗氧化酶状态的影响。
