Effect of metformin on glutathione and magnesium in normal and streptozotocin‐induced diabetic rats

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Abstract
Recently there has been growing interest in magnesium deficiency and its correlation with coronary artery disease, chronic complications of diabetes mellitus and antioxidant enzyme activity. Hypomagnesemia is a common association of diabetes mellitus, and the blood glutathione (GSH) level is significantly lower in both conditions. Metformin (Met), 'an oral antihyperglycemic drug' frequently used in the management of diabetes mellitus outside the USA, has been shown to have an insulin-like action. The purpose of this study was to investigate the effect of oral administration of Met (60 mg kg(-1)) for 14 days on GSH and magnesium levels in blood, liver and heart of normal and streptozotocin-induced diabetic Wistar rats. Diabetes was induced by an i.p. injection of streptozotocin (60 mg kg(-1)). Our results showed that Met did not affect fasting serum glucose concentration in non-diabetic animals but reduced it significantly in diabetic animals. Serum and liver magnesium levels were significantly decreased in the untreated diabetic group compared with the normal group. Treatment with Met improved liver magnesium concentration in the diabetic group only. It has no effect on serum magnesium in diabetic or non-diabetic rats. Heart magnesium levels showed non-significant changes in all groups. In diabetic animals a significant decrease of GSH in both blood and liver was observed. Treatment with Met increased these levels significantly, with a similar effect on GSH levels in non-diabetic rats. There were no significant changes in heart GSH levels in any of the groups. This study demonstrates that oral Met therapy improves the altered levels of magnesium and GSH in diabetic rats.