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

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

Fatih Özçelik  1 , Fatih Hacımustafaoğlu  2 , Alpaslan Tanoğlu  3
Affiliations

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

Fatih Özçelik et al. Turk J Med Sci. 2022 Feb.

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.

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Conflict of interest statement

Conflict of interest statement

The authors declare that they have no conflicts of interest. No financial support was received from any institution or company for this study. No financial support was received from any institution or company except our own institution (The University of Health Sciences, Turkey) for this study. We do not have financial and business conflicts of interest with our employer or other organizations.

Figures

Figure 1
Figure 1
Box plots graph comparing NK-cell activities, IL-6 levels and MR-proADM levels in control group (group I), diabetic group (group II), DM + melatonin (group III) and DM + resveratrol group (group IV). The NK-cell activities, IL-6 levels, and MR-proADM levels were compared with the Kruskal-Wallis test (nonparametric ANOVA) due to the number of samples in the groups. A) While NK-cell activity was lower in the diabetic group compared to the control group, NK-cell activity increased again in the diabetic groups receiving melatonin and resveratrol. B) IL-6 levels appear to be higher in the diabetic group compared to the control group. However, the values in the diabetic groups administered melatonin and resveratrol are not different from the control group. C) MR-proADM levels are lower in the diabetic group compared to the control group. However, there is no difference in the diabetic groups receiving melatonin and resveratrol compared to the control group. Compared to the diabetic group, rats receiving melatonin had higher MR-proADM levels.
Figure 2
Figure 2
Box plots graph comparing control group (group I), diabetic group (group II), DM + melatonin (group III), and DM + resveratrol groups (group IV) in terms of TNF-α, TAS and TOS levels. There is no difference between the groups in terms of these parameters.
Figure 3
Figure 3
Correlation plot showing the relationship between NK-cell activity, MR-proADM, and IL-6 levels. The graph shows the direct proportional correlation of NK cell activity with MR-proADM.
See this image and copyright information in PMC

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