Resveratrol Has Histone 4 and Beta-Defensin 1-Mediated Favorable Biotherapeutic Effects on Liver and Other Target Organs in Diabetic Rats.

BACKGROUND/AIMS:  It was aimed to investigate the biochemical and histopathological effects of resveratrol and melatonin, via histone H4 and ß-defensin 1, in diabetic rats. MATERIALS AND METHODS:  Twenty-four Sprague-Dawley male rats were categorized into 4 groups, with 6 rats in each group (control, diabetes mellitus, melatonin - diabetes mellitus, and resveratrol+diabetes mellitus). Diabetes was formed by giving streptozotocin to all groups except the control group. Melatonin, 5 mg/kg/day, was given to the melatonin - diabetes mellitus group, and resveratrol, 5 mg/kg/day, was given to the resveratrol+diabetes mellitus group via intraperitoneally for 3 weeks. Interleukin-1 beta, tumor necrosis factor alpha, histone H4, and ß-defensin 1 levels were measured in the blood of all rats. The lung, liver, and kidney tissue of all rats were performed as histopathological examinations. RESULTS:  Whereas there was no difference between the other groups (P >.05), interleukin-1 beta levels of the diabetes mellitus group were found to be significantly higher compared with the control group (5.02 ± 2.15 vs. 2.38 ± 0.72 ng/mL; P < .05). Whereas histone H4 levels of the diabetes mellitus group were higher compared with the control and resveratrol+diabetes mellitus groups (7.53 ± 3.30 vs. 2.97 ± 1.57 and 3.06 ± 1.57 ng/mL; P <.05), the ß-defensin 1 levels of the diabetes mellitus group were lower compared with control and resveratrol+diabetes mellitus groups (7.6 ± 2.8 vs. 21.6 ± 5.5 and 18.8 ± 7.4 ng/mL; P <.05). ß-Defensin 1 levels were moderately inversely correlated with interleukin-1 beta and histone H4 levels (rs > -0.50, P < .01). Histopathological changes found in favor of target cell damage in the diabetes mellitus group were not observed in resveratrol+diabetes mellitus group. CONCLUSION:  Resveratrol may be used as a biotherapeutic agent, which significantly reduces diabetes-induced histone H4 and interleukin-1 beta-mediated liver and other target organ damage.

Effect of melatonin on low and high dose radiotherapy induced thyroid injury.

We investigated the radioprotective effect of melatonin (MEL) against thyroid gland damage in rats caused by flattening filter (FF) and flattening filter free (FFF) single dose X-ray beams. We used 48 female rats divided into six groups of eight: group 1, untreated control group; group 2, MEL treated group; group 3, FF-low dose rate radiotherapy (FF-LDR) group; group 4, FF-LDR + MEL group; group 5, FFF-high dose rate radiotherapy (FFF-HDR) group; group 6, FFF-HDR + MEL group. Groups 2, 4 and 6 rats were injected intraperitoneally (i.p.) with 10 mg/kg MEL 15 min before exposure to radiation. The head and neck regions of each rat in groups 3 and 5 and groups 4 and 6 were irradiated with 16 Gy at 6 MV X-ray in FF and FFF beam modes. The histopathology of the thyroid gland and salient biochemical parameters were assessed in all rats 10 days after radiotherapy. We found increased inflammation, vacuolization, degradation, swelling and necrosis, and M30 apoptosis and M65 necrosis indicators in groups 3 and 5 compared to group 1; however, we found significant reductions in histopathological and biochemical parameters following application of MEL. MEL treatment before FF-LDR and FFF-HDR radiotherapy minimized thyroid gland injury due to irradiation.

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

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).