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Oxidative stress in diabetic rats induced by streptozotocin: Protective effects of melatonin
Author(s) -
Montilla Pedro López,
Vargas José Fresno,
Túnez Isaac Fiñana,
Carmen M.,
Agueda Muñoz,
Valdelvira M. Elías Díaz,
Cabrera Emilio Sãnchez
Publication year - 1998
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.1998.tb00545.x
Subject(s) - melatonin , medicine , endocrinology , fructosamine , oxidative stress , streptozotocin , chemistry , diabetes mellitus , malondialdehyde , hemoglobin , glutathione , lipid peroxidation , biochemistry , enzyme
We have studied the effect of the administration of two doses of melatonin (melatonin 100 and melatonin 200 μg/kg bw) on diabetes and oxidative stress experimentally induced by the injection of streptozotocin (STZ) in female Wistar rats. STZ was injected as a single dose (60 mg/kg i.p. in buffered citrate solution, pH 4.0) and melatonin (melatonin 100, 100 μg/kg/day i.p.; melatonin 200, 200 μg/kg/day i.p.) beginning 3 days before diabetes induction and continuing until the end of the study (8 weeks). The parameters analysed to evaluate oxidative stress and the diabetic state were a) for oxidative stress, changes of lipoperoxides (i.e., malondialdehyde, MDA) in plasma and erythrocytes and the changes in reduced glutathione (GSH) in erythrocytes and b) for diabetes, changes in glycemia, lipids (triglycerides: TG; total cholesterol: TC; HDL‐cholesterol, HDL‐c), percentage of glycosylated hemoglobin (Hb%), and plasma fructosamine. The injection of STZ caused significant increases in the levels of glycemia, percentage of glycosylated hemoglobin, fructosamine, cholesterol, triglycerides, and lipoperoxides in plasma and erythrocytes, whereas it decreased the levels of HDL‐c and the GSH content in erythrocytes. The melatonin 100 dose reduced significantly all these increases, except the percentage of glycosylated hemoglobin. With regard to the decreases of plasma HDL‐c and GSH content in erythrocytes, this melatonin dose returned them to normal levels. The melatonin 200 dose produced similar changes, though the effects were especially noticeable in the decrease of glycemia (55% vs. diabetes), percentage of hemoglobin ( P < 0.001 vs diabetes), and fructosamine (31% vs. diabetes). This dose also reversed the decreases of HDL‐c and GSH in erythrocytes. Both doses of melatonin caused significant reduction of the percentage of glycosylated hemoglobin in those groups that were non‐diabetic. These illustrate the protective effect of melatonin against oxidative stress and the severity of diabetes induced by STZ. In particular, this study confirms two facts: 1) the powerful antioxidant action of this pineal indole and 2) the importance of the severity of oxidative stress to maintain hyperglycemia and protein glycosylation, two pathogenetic cornerstones indicative of diabetic complications. Melatonin reduces remarkably the degree of lipoperoxidation, hyperglycemia, and protein glycosylation, which gives hope to a promising perspective of this product, together with other biological antioxidants, in the treatment of diabetic complications where oxidative stress, either in a high or in a low degree, is present.