Bykov I M, Popov K A, Tsymbalyuk I Yu, Dzhimak S S, Shashkov D I, Malyshko V V, Baryshev M G
Kuban State Medical University, Krasnodar.
Kuban State University, Krasnodar.
Vopr Pitan. 2017;86(3):68-76. doi: 10.24411/0042-8833-2017-00047. Epub 2017 May 2.
The research concerning the effect of the remedies with the different antioxidant mechanisms on the indices of carbohydrate and lipid metabolism as well as the thiol link of the antioxidant system and the functional detoxication system in modeling conditions of the decompensated alloxan diabetes mellitus have been presented. The research was performed on 105 white nonlinear male-rats with initial body weight (b.w.) 200-230 g, divided into seven groups. Group 1 has consisted of the intact animals. Group 2 (the comparison group) has consisted of the animals suffering from the severe alloxan diabetes mellitus (intraperitoneal administration of alloxan monohydrate at 10 mg/100 g b.w. three times, with an interval of one day, against fasting) without correction. In groups 3-7 diabetes mellitus has also been modeled. The animals of group 3 were fed by the diet with the supplement containing the antioxidant complex with high content of carotenoid substances (1 mg lutein per day, orally for a month before simulations of diabetes mellitus and for a month after). The animals of group 4 have been given the sodium dichloroacetate (15 mg/100g bw) with drinking water for the month before and a month after the modeling of diabetes. The animals of group 5 have been injected with the reduced glutathione (15 mg/100 g of b.w.) daily one week prior to administration of alloxan and until the end of the experiment, the animals of group 6 have been injected with the quercithin (10 mg/100 g of b.w.) and the rats of group 7 have been given the water with the reduced content of deuterium (91 mg/l) instead of the usual drinking water. The development of experimental alloxan diabetes mellitus in rats has been accompanied by the increase in blood plasma of glucose concentration by 6.9-fold, cholesterol and lipoproteins of low density by 66 and 100% respectively. The compensatory activity increase of the antiradical protective enzymes (glutathione peroxidase and glutathione reductase) as well as the concentration decrease of reduced glutathione in erythrocytes by 11% have been revealed. According to the data concerning the level of the molecules with medium and low mass in blood plasma as well as in erythrocytes, the evident endogenous intoxication has taken place. The performed researches have proved the presence of the significant hypoglycemic effect of the usage of sodium dichloroacetate, of the water with the reduced content of deuterium and of quercithin - the glucose concentration in these groups was lower than in the comparison group by 36, 33 and 47% respectively. In the same groups as well as in the group of rats injected with glutathione the hypolipidemic effect of various manifestation degree has been detected, the most evident in animals from group 7 in which all the indices except triglycerides haven't differed from indices of the control group. The usage of various corrective methods has also assisted the adequate functioning of the antioxidant system that has been proved by the normalization of glutathione content except of groups 3 and 6 in which its concentration was lower than the control indices by 25 and 12% respectively. Endogenous intoxication has been significantly lower in groups 4, 5 and 7 in which the level of molecular of medium and low mass in blood plasma was normal and only in erythrocyte mass was increased by 49-74% than in the control group. Thus, the data obtained prove the usage availability of the antioxidant remedies in the complex therapy in patients suffering from the diabetes mellitus. The most interesting is the usage of antioxidants with the indirect mechanism of action, i.e. the water with the reduced content of deuterium and sodium dichloroacetate. Quercithin and the reduced glutathione deserve attention as well, and considering the hypoglycemic effect of the first one and the metabolic effects of glutathione aimed at the functioning maintenance of the non-specific organism resistance, the possibility of the combined usage of both antioxidants should be taken into account.
本文介绍了在实验性糖尿病失代偿模型条件下,研究具有不同抗氧化机制的药物对碳水化合物和脂质代谢指标以及抗氧化系统的硫醇连接和功能性解毒系统的影响。实验选用105只初始体重为200 - 230 g的白色非线性雄性大鼠,分为七组。第1组为正常动物组。第2组(对照组)为患有严重四氧嘧啶糖尿病的动物(禁食状态下,腹腔注射10 mg/100 g体重的一水合四氧嘧啶,间隔一天,共注射三次),未进行治疗。第3 - 7组也建立了糖尿病模型。第3组动物在模拟糖尿病前一个月及模拟后一个月,每日经口给予含高含量类胡萝卜素物质的抗氧化复合物补充剂(每天1 mg叶黄素)。第4组动物在糖尿病建模前一个月及建模后一个月,通过饮用水给予二氯乙酸钠(15 mg/100 g体重)。第5组动物在注射四氧嘧啶前一周至实验结束,每日注射还原型谷胱甘肽(15 mg/100 g体重)。第6组动物注射槲皮素(10 mg/100 g体重)。第7组动物饮用低氘水(91 mg/L)替代普通饮用水。大鼠实验性四氧嘧啶糖尿病的发展伴随着血浆葡萄糖浓度升高6.9倍,胆固醇和低密度脂蛋白分别升高66%和100%。同时发现抗自由基保护酶(谷胱甘肽过氧化物酶和谷胱甘肽还原酶)的代偿活性增加,红细胞中还原型谷胱甘肽浓度降低11%。根据血浆和红细胞中中低分子量分子水平的数据,明显存在内源性中毒。所进行的研究证明,使用二氯乙酸钠、低氘水和槲皮素具有显著的降血糖作用,这些组中的葡萄糖浓度分别比对照组低36%、33%和47%。在相同组以及注射谷胱甘肽的大鼠组中,检测到不同程度表现的降血脂作用,在第7组动物中最为明显,该组除甘油三酯外的所有指标与对照组指标无差异。使用各种纠正方法也有助于抗氧化系统的正常功能,除第3组和第6组外,其他组谷胱甘肽含量均恢复正常,其中第3组和第6组谷胱甘肽浓度分别比对照组指标低25%和12%。第4、5和7组的内源性中毒明显低于对照组,这三组血浆中中低分子量分子水平正常,仅红细胞质量比对照组增加49 - 74%。因此,所获得的数据证明了抗氧化药物在糖尿病患者综合治疗中的应用价值。最有趣的是使用具有间接作用机制的抗氧化剂,即低氘水和二氯乙酸钠。槲皮素和还原型谷胱甘肽也值得关注,考虑到前者的降血糖作用和谷胱甘肽对机体非特异性抵抗力维持功能的代谢作用,应考虑联合使用这两种抗氧化剂的可能性。