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Abstract
Today, vitamin D3 deficiency (cholecalciferol) and impaired signaling through vitamin D receptors are considered one of the risk factors for hepatopathy development on the background of type 2 diabetes (T2D). The anti-inflammatory and hepatoprotective effects of vitamin D3 and in general, a scientific justification for the possibility of its effective use in the clinic of T2D are actively highlighted in the literature, but the specific mechanisms remain insufficiently clarified. The aim is to study the effect of vitamin D3 on the mRNA expression level of key components of the hepatocellular vitamin D-auto-/paracrine system and the cytokine pathway tumor necrosis factor alpha/nuclear factor kappa-light-chain-enhancer of activated B cells (TNF-α/NF-κB) in experimental T2D. Material and methods. T2D was induced in male Wistar rats by a combination of a high-fat diet and a low dose of streptozotocin (25 mg/kg). Measurements of triacylglycerols, cholesterol, higher fatty acids, total lipids and total serum cholesterol were performed by standard biochemical methods. The content of 25(OH)D was determined by enzyme-linked immunosorbent assay. Analysis of mRNA expression of RelA, Iκb, Tnf-α, Cyp27a1, Cyp2r1, Cyp27b1 and Vdr genes was performed by real-time quantitative polymerase chain reaction. Results. Experimental T2D was accompanied by vitamin D deficiency in the organism of experimental animals and the development of diabetic hepatopathy, as evidenced by increased alanine aminotransferase activity and also by the accumulation of cholesterol, triacylglycerols and higher fatty acids in the blood of animals. A decrease in the mRNA content of key components of the vitamin D-auto-/paracrine system in the liver of diabetic animals led to disruption of signaling through vitamin D receptors and activation of the cytokine pathway
TNF-α/NF-κB. Administration of vitamin D3 at a dose of 800 IU/kg for 30 days in animals with T2D significantly normalized the expression of vitamin D receptors and enzymes of metabolic conversion of vitamin D in liver tissue and reduced the expression of pro-inflammatory factors — NF-κB and TNF-α. Conclusion. Potentially, vitamin D3 used in the treatment of T2D may have a hepatoprotective effect by normalizing the functional state of vitamin D-auto-/paracrine system of the liver and modulating the pro-inflammatory processes dependent on nuclear factor κB.
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