Saeed Mamoona, Saleem Uzma, Anwar Fareeha, Ahmad Bashir, Anwar Asifa
Department of Pharmacy, Riphah Institute of Pharmaceutical Sciences, Riphah International University Lahore Campus, Lahore 54000, Pakistan.
Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad 38000, Pakistan.
ACS Omega. 2020 Mar 2;5(10):4953-4961. doi: 10.1021/acsomega.9b03792. eCollection 2020 Mar 17.
Valproic acid (VP) is a very effective therapy for the management of generalized epilepsy. However, its use during pregnancy leads to increased risk of teratogenesis and cognitive malfunctioning in postnatal growing children. Antioxidants are used commercially as a palliative therapy. This study compares the different antioxidants effects on VP-induced teratogenicity. Pregnant female rats ( = 80) were divided into eight groups ( = 10) as follows: Group I, control group; Group II, disease group valproic acid (500 mg/kg); Groups III and IV, treated with 2000 and 8000 mg/kg vitamin C, respectively; Groups V and VI, treated with selenium 100 and 200 μg/kg dose, respectively; and Groups VII and VIII, administered grape seed extract 300 and 600 mg/kg, respectively. Groups III-VIII received valproic acid (500 mg/kg) along with their respective treatments. All treatments were given via an oral route. The fetuses were double stained, and levels of superoxide dismutase (SOD), catalase (CAT), nitrite, glutathione (GSH), and malondialdehyde (MDA) were estimated. Resorption rate was significantly reduced in Vit. C treated groups at both dose levels. Maternal death rate was decreased remarkably in all treatment groups. Vit. C at a high dose (8000 mg/kg) and grape seed at a high dose (600 mg/kg) significantly reduced the incidence of delayed cervical ossification. The values of MDA were significantly reduced in all groups except the Vit. C group (2000 mg/kg). However, no significant elevation was observed in the values of SOD, CAT, and GSH. The current study concluded that vitamin C at a high dose (8000 mg/kg) and grape seed extract at a high dose (600 mg/kg) had partially protected the fetuses exposed to VP.
丙戊酸（VP）是治疗全身性癫痫的一种非常有效的疗法。然而，在孕期使用该药物会增加致畸风险以及产后成长中儿童出现认知功能障碍的风险。抗氧化剂在商业上被用作一种姑息疗法。本研究比较了不同抗氧化剂对VP诱导的致畸性的影响。将80只怀孕的雌性大鼠分为八组（每组10只），如下：第一组为对照组；第二组为疾病组（丙戊酸，500毫克/千克）；第三组和第四组分别用2000毫克/千克和8000毫克/千克的维生素C进行治疗；第五组和第六组分别用100微克/千克和200微克/千克剂量的硒进行治疗；第七组和第八组分别给予300毫克/千克和600毫克/千克的葡萄籽提取物。第三组至第八组在接受各自治疗的同时给予丙戊酸（500毫克/千克）。所有治疗均通过口服途径给药。对胎儿进行双重染色，并估计超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、亚硝酸盐、谷胱甘肽（GSH）和丙二醛（MDA）的水平。在两个剂量水平的维生素C治疗组中，吸收率均显著降低。所有治疗组的母体死亡率均显著降低。高剂量（8000毫克/千克）的维生素C和高剂量（600毫克/千克）的葡萄籽显著降低了颈椎骨化延迟的发生率。除维生素C组（2000毫克/千克）外，所有组的MDA值均显著降低。然而，SOD、CAT和GSH的值未观察到显著升高。本研究得出结论，高剂量（8000毫克/千克）的维生素C和高剂量（600毫克/千克）的葡萄籽提取物对暴露于VP的胎儿有部分保护作用。
