Melatonin ameliorates low-grade inflammation and oxidative stress in young Zucker diabetic fatty rats

Ahmad Agil, Russel J. Reiter, Aroa Jiménez-Aranda, Ruth Ibán-Arias, Miguel Navarro-Alarcón, Juan Antonio Marchal, Abdu Adem, Gumersindo Fernández-Vázquez

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117 Citations (Scopus)


The aim of this study was to investigate the effects of melatonin on low-grade inflammation and oxidative stress in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n = 30) and lean littermates (ZL) (n = 30) were used. At 6 wk of age, both lean and fatty animals were subdivided into three groups, each composed of 10 rats: naive (N), vehicle treated (V), and melatonin treated (M) (10 mg/kg/day) for 6 wk. Vehicle and melatonin were added to the drinking water. Pro-inflammatory state was evaluated by plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Also, oxidative stress was assessed by plasma lipid peroxidation (LPO), both basal and after Fe2+/H2O2 inducement. ZDF rats exhibited higher levels of IL-6 (112.4 ± 1.5 pg/mL), TNF-α (11.0 ± 0.1 pg/mL) and CRP (828 ± 16.0 μg/mL) compared with lean rats (IL-6, 89.9 ± 1.0, P < 0.01; TNF-α, 9.7 ± 0.4, P < 0.01; CRP, 508 ± 21.5, P < 0.001). Melatonin lowered IL-6 (10%, P < 0.05), TNF-α (10%, P < 0.05), and CRP (21%, P < 0.01). Basal and Fe2+/H2O2-induced LPO, expressed as malondialdehyde equivalents (μmol/L), were higher in ZDF rats (basal, 3.2 ± 0.1 versus 2.5 ± 0.1 in ZL, P < 0.01; Fe2+/H 2O2-induced, 8.7 ± 0.2 versus 5.5 ± 0.3 in ZL; P < 0.001). Melatonin improved basal LPO (15%, P < 0.05) in ZDF rats, and Fe2+/H2O2-induced LPO in both ZL (15.2%, P < 0.01) and ZDF rats (39%, P < 0.001). These results demonstrated that oral melatonin administration ameliorates the pro-inflammatory state and oxidative stress, which underlie the development of insulin resistance and their consequences, metabolic syndrome, diabetes, and cardiovascular disease.

Original languageEnglish
Pages (from-to)381-388
Number of pages8
JournalJournal of Pineal Research
Issue number4
Publication statusPublished - May 2013


  • Low-grade inflammation
  • Melatonin
  • Oxidative stress
  • Zucker diabetic fatty rats

ASJC Scopus subject areas

  • Endocrinology


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