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二甲双胍与维生素C长期联合给药对正常大鼠血糖和血脂浓度的影响。

Effect of chronic co-administration of metformin and vitamin C on plasma glucose and lipid concentrations in normal rats.

作者信息

Adeneye A A, Amole O O, Agbaje E O, Izegbu M C, Elias S O

机构信息

Department of Pharmacology, Lagos State University, College of Medicine, Ikeja, Lagos, Nigeria.

出版信息

Afr J Med Med Sci. 2007 Jun;36(2):149-54.

Abstract

In clinical setting, uncomplicated diabetes mellitus type 2 is managed with anti-oxidants (e.g. ascorbic acid, alpha-tocopherol, etc.) with standard oral hypoglycaemic agents, which is aimed at limiting its glucose auto-oxidation and lipid peroxidation complications. The current study is an experimental animal study aimed at investigating the effect of co-administration of metformin and ascorbic acid (Vitamin C) on plasma glucose and lipid levels in non-diabetic rats which could serve as a template for future studies in this area. The hypoglycaemic and hypolipidaemic activities of metformin, ascorbic acid, and metformin-ascorbic acid combination were studied in 4 groups consisting of 6 rats per group and weighing 120 - 155 g, by administering oral doses of 5, 10 and 15 (for co-administration) mg/kg/day of the drugs, respectively, for 30 days. The acute oral toxicity of the combination was also conducted using limit dose test of Up and Down Procedure of Acute Oral Toxicity test. Results of the study showed that metformin and metformin-ascorbic acid combination induced significant and comparable hypoglycaemia. The drug combination also lowered plasma total cholesterol, low density lipoprotein-cholesterol (LDL-c), very low density lipoprotein-cholesterol (VLDL-c) significantly but had no effect on plasma high density lipoprotein-cholesterol (HDL-c). The LD50 estimate of the drug combination was greater than 5000 mg/kg body weight/oral route. The results of this study suggest the drug combination could have hypoglycaemic and lipid-lowering effects.

摘要

在临床环境中,单纯性2型糖尿病采用抗氧化剂(如抗坏血酸、α-生育酚等)与标准口服降糖药联合治疗,目的是限制其葡萄糖自氧化和脂质过氧化并发症。本研究是一项实验动物研究,旨在探讨二甲双胍与抗坏血酸(维生素C)联合给药对非糖尿病大鼠血糖和血脂水平的影响,可为该领域未来的研究提供模板。通过分别给予5、10和15(联合给药)mg/kg/天的药物口服剂量,连续30天,对4组每组6只体重120 - 155 g的大鼠研究了二甲双胍、抗坏血酸以及二甲双胍 - 抗坏血酸组合的降血糖和降血脂活性。还使用急性经口毒性试验的上下法极限剂量试验对该组合进行了急性经口毒性研究。研究结果表明,二甲双胍和二甲双胍 - 抗坏血酸组合均诱导了显著且相当的低血糖。该药物组合还显著降低了血浆总胆固醇、低密度脂蛋白胆固醇(LDL - c)、极低密度脂蛋白胆固醇(VLDL - c),但对血浆高密度脂蛋白胆固醇(HDL - c)没有影响。该药物组合的半数致死量估计大于5000 mg/kg体重/经口途径。本研究结果表明该药物组合可能具有降血糖和降脂作用。

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