Nutrition. 2013 May;29(5):785-9.

Antioxidant activity of melatonin in diabetes in relation to the regulation and levels of plasma Cu, Zn, Fe, Mn, and Se in Zucker diabetic fatty rats.

Navarro-Alarcon M, Ruiz-Ojeda FJ, Blanca-Herrera RM, Agil A.

Department of Nutrition and Food Science, School of Pharmacy, University of Granada, Granada, Spain.




To study the antioxidant activity of melatonin in diabetes in relation to the regulation and levels of plasma copper (Cu), zinc (Zn), iron (Fe), manganese (Mn), and selenium (Se) in Zucker diabetic fatty (ZDF) and lean (ZL) rats.


At 6 wk of age, both ZDF (n = 30) and ZL (n = 30) animals were subdivided into three groups: control (C) (n = 10), vehicle (V) (n = 10), and melatonin-treated (M) (10 mg/kg/d; n = 10) rats for a 6-wk period. At the end of treatment period, plasma mineral levels were measured by flame (Cu, Zn, and Fe), electrothermal (Mn), and hydride generation (Se) atomic absorption spectrometry.


ZDF rats had significantly higher Cu, Fe, and Mn plasma levels than did ZL rats (P < 0.05). No significant differences were found between control and vehicle groups (P > 0.05). Melatonin treatment did not influence plasma levels of these antioxidant minerals (Cu, Zn, Fe, and Mn) in ZDF groups (M-ZDF versus C-ZDF group) and ZL (M-ZL versus C-ZL group) rats with the exception of Zn, whose mean plasma level was lower in the M-ZL versus C-ZL group. However, plasma Se levels increased significantly (P < 0.05) after melatonin supplementation in both groups (M-ZDF and M-ZL).


The higher mean plasma Cu, Fe, and Mn levels in the ZDF group are related to the enhanced oxidative stress in diabetes and obesity. Melatonin administration significantly enhanced plasma Se levels in both groups (M-ZDF and M-ZL). This is the first study to report that melatonin treatment increases plasma Se levels.

Copyright © 2013 Elsevier Inc.

PMID: 23352467



It has been reported that the antioxidant capacity of melatonin occurs through multiple direct and indirect mechanisms among which the induction of antioxidant enzymes (glutathione peroxidase [GSH-Px], catalase [CAT] and superoxide dismutase [SOD], for which Se, Fe, Zn-Cu and Mn act as enzymatic cofactors, respectively) has been reported. This antioxidant action has been associated with anti-diabetic, onco-static, immune-modulatory, anti-aging and neuro-protective effects[1, 2].

Navarro-Alarcon-1However, very little information is nowadays available on the possible influence exerted by the melatonin on tissue and blood levels of minerals involved in the oxidative metabolism namely Zn, Cu, Mn, Se and Fe. In this study, we have measured the plasma levels of Cu, Zn, Fe, Mn and Se in ZDF and ZL rats supplemented with melatonin. As conclusion, the treatment with melatonin (10 mg/kg weight/day) did not regulate plasma homeostasis of antioxidant minerals like Zn, Cu, Fe and Mn in young male ZDF rats. The mean Cu, Fe and Mn plasma levels measured in the ZDF group were higher than those determined in ZL rats; this finding is related with the enhanced oxidative stress characteristic of diabetes and obesity. The melatonin treatment did not change these enhanced plasma levels for Cu, Fe and Mn, finding that could be related with the secondarily enhancement in the activity of antioxidant enzymes (namely cytoplasm and mitochondrial SOD and CAT, for Zn-Cu, Mn and Fe, respectively) reported in several studies after melatonin supplementation. The melatonin antioxidant capacity in diabetes is not associated with the regulation of plasma levels of Cu, Zn, Fe and Mn. Melatonin administration notably enhances plasma Se levels in both groups of rats (M-ZDF and M-ZL). This finding is related with Se releasing from body stores to be employed in the synthesis of the GPx enzyme, whose activity enhancement after melatonin treatment has been reported in several studies. In our knowledge, this is the first study to report that melatonin treatment firstly increases plasma Se levels in order to secondarily increase the GPx activity.



1- Agi, A, Reiter RJ, Jiménez-Aranda A; Ibáñez-Arias R; Navarro-Alarcón M, Marchal JA, Adem A, Fernández-Vázquez G. Melatonin ameliorates low-grade inflammation and oxidative stress in young Zucker diabetic fatty rats. J. Pineal Res. 2013; 54: 381-8.

2- Navarro-Alarcón M, Ruiz-Ojeda FJ, Blanca-Herrera RM, Kaki A, Adem A, Agil A. Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats. Food & Funct. 2013;doi:10.1039/C3FO60389J.

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