EFFECT OF THE GABA DERIVATIVE SUCCICARD ON THE LIPID AND CARBOHYDRATE METABOLISM IN THE OFFSPRING OF RATS WITH EXPERIMENTAL PREECLAMPSIA IN EARLY AND LATE ONTOGENY

E. A. Muzyko, V. Perfilova, A. Nesterova, K. V. Suvorin, I. Tyurenkov
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Abstract

Maternal preeclampsia can bring about metabolic disorders in the offspring at different stages of ontogeny. Up to date, no ways of preventive pharmacological correction of lipid and carbohydrate metabolism disorders developing in different periods of ontogeny in the children born to mothers with this pregnancy complication, have been developed.The aim of the experiment was to study the effect of the gamma-aminobutyric acid derivative succicard (22 mg/kg) and its reference drug pantogam (50 mg) administered per os in the course of treatment in puberty (from 40 to 70 days after birth), on the parameters of lipid and carbohydrate metabolism in the offspring of the rats with experimental preeclampsia, in different periods of ontogeny.Materials and methods. To assess the activity of lipid and carbohydrate metabolism in the offspring, an oral glucose tolerance test was performed at 40 days, 3, 6, 12 and 18 months of age. The level of glycosylated hemoglobin was measured at the age of 6, 12, and 18 months, and the concentrations of total cholesterol, high-density lipoprotein cholesterol and triglycerides were tested at 40 days, 3, 6, 12, and 18 months of age.Results. The offspring of the rats with experimental preeclampsia, were found out to have lipid and carbohydrate metabolism disturbances during early (40 days and 3 months of age) and late (6, 12, and 18 months of age) ontogeny. In comparison with the offspring of healthy females, these disturbances were manifested by significantly higher levels of glucose revealed during the oral glucose tolerance test, by high glycosylated hemoglobin in males, and with elevated concentration of total cholesterol and triglycerides and a low level of high-density lipoprotein cholesterol in the negative control rats. Both the gamma-aminobutyric acid derivative succicard and its reference drug pantogam, reduced the negative effect of experimental preeclampsia on lipid and carbohydrate metabolism in the offspring in late ontogeny (6, 12 and 18 months of age). The effectiveness of succicard was either higher or comparable with pantogam.Conclusion. Thus, the negative impact manifestations of experimental preeclampsia on lipid and carbohydrate metabolism, are revealed in the offspring in early (40 days and 3 months) and late (6, 12 and 18 months of age) ontogeny. The gamma-aminobutyric acid derivative succicard reduces the negative effect of experimental preeclampsia. Based on this finding, the drug implies the possibility of the development of a safe and highly effective medicine for preventive correction of lipid and carbohydrate metabolism disorders in the children born to mothers with preeclampsia.
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gaba衍生物琥珀酸对实验性子痫前期和晚期子痫大鼠后代脂质和碳水化合物代谢的影响
母体子痫前期可导致子代在个体发育的不同阶段出现代谢紊乱。到目前为止,还没有任何方法可以对患有这种妊娠并发症的母亲所生的孩子在个体发育的不同时期发生的脂质和碳水化合物代谢紊乱进行预防性药物纠正。本实验旨在研究γ -氨基丁酸衍生物琥珀酸酯(22 mg/kg)及其参比药物pantogam (50 mg)在青春期(出生后40 ~ 70天)给药过程中对实验性子痫前期大鼠子代不同发育时期脂质和碳水化合物代谢参数的影响。材料和方法。为了评估后代的脂质和碳水化合物代谢活性,在40天、3个月、6个月、12个月和18个月时进行了口服葡萄糖耐量试验。测定6、12、18月龄时的糖化血红蛋白水平,测定40天、3、6、12、18月龄时的总胆固醇、高密度脂蛋白胆固醇和甘油三酯浓度。实验子痫前期大鼠的子代在发育早期(40天和3个月)和晚期(6、12和18个月)均存在脂质和碳水化合物代谢紊乱。与健康雌性的后代相比,这些干扰表现为口服糖耐量试验时葡萄糖水平明显升高,雄性糖基化血红蛋白升高,阴性对照大鼠总胆固醇和甘油三酯浓度升高,高密度脂蛋白胆固醇水平降低。γ -氨基丁酸衍生物琥珀酸及其参比药物pantogam均可降低实验性子痫前期对子代个体发育晚期(6、12和18个月)脂质和碳水化合物代谢的负面影响。琥珀卡的治疗效果高于潘托甘或与潘托甘相当。因此,实验性子痫前期对子代脂质和碳水化合物代谢的负面影响表现在子代发育早期(40天和3个月)和晚期(6、12和18个月)。γ -氨基丁酸衍生物琥珀酸可减少实验性子痫前期的负面影响。基于这一发现,该药物意味着开发一种安全高效的药物来预防纠正患有先兆子痫的母亲所生的孩子的脂质和碳水化合物代谢紊乱的可能性。
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