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Information × Registration Number 0224U032702, (0123U102781) , R & D reports Title Cellular and molecular mechanisms of vitamin D3 hepatoprotective action in non-alcoholic fatty liver disease associated with experimental type 2 diabetes mellitus popup.stage_title Інтенсивніть прозапальних, проліферативно-регенеративних процесів та апоптичної загибелі клітин печінки за ЦД2-індукованої НАЖХП та при коригувальній дії вітаміну D3. Cтан вітамін D-ауто/паракринної системи у печінці за ЦД2 з НАЖХП та при корекції вітаміном D3. Head Shymanskyi Ihor O., Кандидат біологічних наук Registration Date 02-12-2024 Organization Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine popup.description1 To more fully elucidate the mechanisms of the hepatoprotective action of vitamin D3 in NAFLD associated with experimental type 2 diabetes mellitus, based on the study of the macro- and microstructure of the liver, the intensity of free radical processes, ER stress, autophagy, inflammation, apoptosis and cell proliferation in liver tissue depending on the state of the vitamin D auto-/paracrine system, as well as its modulating effects on RANKL/RANK/OPG and NF-κBmediated cellular signaling. popup.description2 The goal of the 2nd stage of the project was to establish the relationship between the level of proliferative-regenerative processes and apoptotic cell death in connection with low-gradient inflammation and expression of key components of the vitamin D3 signaling system in the liver of rats with diabetic hepatosteatosis and following vitamin D3 supplementation. It was found that the development of NAFLD in type 2 diabetes mellitus is associated with significant ROS-dependent expression of the most common NF-κB subunit – p65, with a simultaneous increase in the expression level of the inhibitor of the nuclear factor NF-κB alpha (IκB-α) in liver tissue and activation of NF-κB-mediated transcription of genes, the protein products of which are involved in key events of the inflammatory response, cell proliferation and apoptosis. A diabetes-induced increase in the synthesis of proinflammatory cytokines and apoptosis marker proteins in liver tissue, as well as the percentage of apoptotic and necrotic hepatocytes against the background of transcriptional activation of NF-κB was demonstrated that may indicate the development of low-gradient metabolic inflammation and activation of liver cell death pathways. The involvement of the chemokine molecule MCP-1 as a proinflammatory factor was revealed, and the participation of the adapter protein p66Shc in the development of oxidative stress and apoptotic death of liver cells in NAFLD associated with T2DM was excluded. Vitamin D3 deficiency in animals was shown to be associated with abnormal synthesis of components of the vitamin D3 auto-/paracrine system in the liver. In T2DM, there is a significant suppression of the synthesis of vitamin D3-25-hydroxylase (CYP2R1) and 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1), with a likely compensatory increase in hepatic expression of both 25(OH)D3-1α-hydroxylase CYP27B1 and the vitamin D3 receptor (VDR). Therapeutic administration of vitamin D3 compensated for the diabetes-induced changes Product Description popup.authors Goridko Tetyana M. Krysiuk Iryna P. Lisakovska Olha O. Labudzynskyi Dmytro O. Mezhenska Olha O. Pasichna Elvira P. Siromolot Andrii A. popup.nrat_date 2024-12-02 Close