Modulatory effect of resveratrol and melatonin on natural killer cell activity and adrenomedullin in diabetic rats

Turk J Med Sci. 2022 Feb;52(1):258-267. doi: 10.3906/sag-2104-380. Epub 2022 Feb 22.

Abstract

Background: Epidemiological evidence suggests that diabetes poses a high risk for many chronic diseases, especially cardiovascular diseases, and cancer by stimulating many inflammatory and immunological pathogenic mediators and affecting natural killer (NK)-cell activity. In this study, the effects of melatonin and resveratrol on IL-6, TNF-alpha, oxidant/antioxidant capacity, NK-cell activity, and mid-regional proadrenomedullin (MR-proADM) levels of diabetic rats were investigated.

Methods: In the study, 28 Sprague Dawley rats were randomly divided into the control group (group I) and 3 streptozotocininduced diabetes mellitus (DM) groups (group II, III, and IV), each group consisting of 7 rats. Five mg/kg/day melatonin to group III and 5 mg/kg/day resveratrol (intraperitoneal) to group IV was given. At the end of 3 weeks, NK-cell activity, total antioxidant/oxidant capacity, MR-proADM, IL-6, and TNF-alpha levels were measured in intracardiac blood taken under anesthesia.

Results: NK-cell activity of group II was found lower than group I, group III, and group IV (7.4 ± 2.0 vs. 22.5 ± 11.9, 30.6 ± 22.5 and 20.4 ± 9.1 pg/mL; p = 0.0018, respectively). The difference was more prominent in diabetic rats receiving melatonin (p < 0.01). TNF-alpha levels of group II were higher than the group I (p < 0.05). The MR-proADM levels of group II were found to be lower than the group I and group III (6.4 ± 3.6 vs. 14.4 ± 3.2 and 14.0 ± 4.2 ng/L; p < 0.05, respectively). In addition, NK-cell activity was moderately correlated with MR-proADM (r = 0.5618, p = 0.0019).

Keywords: Diabetes mellitus; melatonin; mid-regional proadrenomedullin; natural killer cell activity; resveratrol.

MeSH terms

  • Adrenomedullin
  • Animals
  • Antioxidants / pharmacology
  • Biomarkers
  • Diabetes Mellitus, Experimental* / drug therapy
  • Interleukin-6
  • Killer Cells, Natural
  • Melatonin* / pharmacology
  • Oxidants
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol / pharmacology
  • Tumor Necrosis Factor-alpha

Substances

  • Melatonin
  • Resveratrol
  • Antioxidants
  • Adrenomedullin
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Oxidants
  • Biomarkers

Grants and funding

This research project was supported by the University of Health Sciences Turkey (Project number: 2019/118).