Effect of vitamin D supplementation on OPG/RANKL signalling activities in endothelial tissue damage in diet-induced diabetic rat model.

BACKGROUND: Type 2 Diabetes Mellitus is a chronic metabolic disease that causes endothelial damage and is an important risk factor for atherosclerosis. In the present study vitamin D3 supplementation in rats was used to determine the role of Osteoprotegerin (OPG)/Receptor activator kB ligand (RANKL) signalling in endothelial damage and changes in the expression levels of genes involved in this pathway. We hypothesized that vitamin D3 supplementation affects OPG and RANKL activity in the aorta. METHODS: Diabetes was induced in rats via injections of 40 mg/kg of streptozotocin followed by a high fructose (10%) diet. Group 2 (healthy) and 4 (diabetic) received 170 IU/kg of vitamin D3 weekly for 5 weeks, while Group 1 (healthy) and 2 (diabetic) received sterile saline. The aortas of each group were collected to analyse mRNA expression using the real-time PCR method and also to evaluate magnesium and calcium levels using inductively coupled plasma mass spectrometry. RESULTS: Opg and Il-1b expression levels were significantly associated with both diabetes and vitamin D3 supplementation in the aortas of the study groups (p ≤ 0.05). Opg mRNA expression was also found to correlate with both Icam-1 and Nos3 mRNA expression levels (r = 0.699, p = 0.001 and r = 0.622, p = 0.003, respectively). In addition, when mineral levels in the aortic tissues were compared among all groups, it was found that the interaction of diabetes and vitamin D3 supplementation significantly affected Mg levels and Mg/Ca ratios. CONCLUSIONS: It is concluded that vitamin D3 supplementation has a modulatory effect on OPG/RANKL activity in the vessel wall by ameliorating endothelial damage in diabetes. This effect may contribute to the regulation of cytokine-mediated vascular homeostasis and mineral deposition in the aorta; therefore, further comprehensive studies are proposed to demonstrate this relationship.

Impact of the Di(2-Ethylhexyl) Phthalate Administration on Trace Element and Mineral Levels in Relation of Kidney and Liver Damage in Rats.

Di(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic polymer in the industry. DEHP may induce reproductive and developmental toxicity, obesity, carcinogenesis and cause abnormal endocrine function in both human and wildlife. The aim of this study was to investigate trace element and mineral levels in relation of kidney and liver damage in DEHP-administered rats. Therefore, prepubertal male rats were dosed with 0, 100, 200, and 400 mg/kg/day of DEHP. At the end of the experiment, trace element and mineral levels, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione S-transferase (GST) enzyme activities were evaluated in the serum, liver, and kidney samples of rats. Furthermore, serum clinical biochemistry parameters, organ/body weight ratios and histological changes were investigated to evaluate impact of DEHP more detailed. Our data indicated that sodium (Na), calcium (Ca), potassium (K), lithium (Li), rubidium (Rb) and cesium (Cs) levels significantly decreased, however iron (Fe) and selenium (Se) concentrations significantly increased in DEHP-administered groups compared to the control in the serum samples. On the other hand, upon DEHP administration, selenium concentration, G6PD and GR activities were significantly elevated, however 6-PGD activity significantly decreased compared to the control group in the kidney samples. Decreased G6PD activity was the only significant change between anti-oxidant enzyme activities in the liver samples. Upon DEHP administration, aberrant serum biochemical parameters have arisen and abnormal histological changes were observed in the kidney and liver tissue. In conclusion, DEHP may induce liver and kidney damage, also result abnormalities in the trace element and mineral levels.

In vitro effects of compounds isolated from Sideritis brevibracteata on bovine kidney cortex glutathione reductase.

Glutathione reductase (GR, E.C 1.6.4.2) is a flavoprotein that catalyzes NADPH-dependent reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH). The aim of this study was to investigate in vitro effects of phenolic compounds isolated from Sideritis brevibracteata on bovine kidney GR. The Sideritis species are widely found in nature and commonly used as medicinal plants. 7-O-glycosides of 8-OH-flavones (hypolaetin, isoscutellarein and 3'-hydroxy-4'-O-methylisoscutellarein) were isolated from aerial parts of Sideritis brevibracteata. These compounds inhibited bovine kidney cortex GR in a concentration-dependent manner. Kinetic characterization of the inhibition was also performed.