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The molecular pathogenesis of diabetic encephalopathy (De), one of the serious complications of diabetes mellitus, is complex. In this study, we examined whether expression levels of SIrT1 and SIrT2 were the key for the development of brain dysfunctions and whether PARP-1 inhibitors could affect the expression of these proteins for prevention the development of De in rats with type 1 diabetes. after 10 weeks of the streptozotocin-induced diabetes mellitus (70 mg/kg), Wistar male rats were treated by i.p. injection with ParP-1 inhibitors, 1.5-isoquinolinediol (ISo) or nicotinamide (Nam) (3 or 100 mg/kg/daily i.p., respectively) for 2 weeks. The rats with blood glucose levels over 19.7 ± 2.1 mmol/l were taken into experiments. Western blots were performed to evaluate effects of PAPR-1 inhibitors on the levels of sirtuins, SIRT1 and SIRT2 expression. Diabetes induced significant reduction of SIRT1 expression and SIRT2 overexpression in brain nuclear extracts of diabetic rats compared to non-diabetic control. In brain, Nam attenuated SIrT2 overexpression in nuclear extracts of diabetic rats and slightly elevated SIRT1 expression, while ISO didn't affect expression of both sirtuins in diabetic rats. Furthermore, it was observed that in brain of diabetic rats, the ratio of free NaD/NaDh couples decreased 3.1-fold compared to non-diabetic control. The administration of ISo increased only slightly the ratio of free NaD/NaDh couples in the brain of diabetic rats while Nam increased this parameter 1.7-fold compared to diabetic rats. Therefore, we concluded that alterations in the expression of SIrT1 and SIrT2 in brain cell nuclei of diabetic rats can lead to the development of brain dysfunctions. one of the neuroprotective mechanisms of Nam action can also be realized through inhibition of SIrT2 expression in brain cell nuclei that down-regulate progression of diabetes-induced alterations and can be a therapeutic option for treatment of brain dysfunctions.

Досліджено вплив специфічних інгібіторів полі(ADP-рибозо)полімерази-1 (PARP-1), зокрема нікотинаміду та 1,5-ізохіноліндіолу на лейкоцити крові щурів за цукрового діабету (цД). із використанням флуоресцентного зонда 2′,7′-дихлородигідрофлуоресцеїн діацетату оцінено продукування активних форм оксигену в лейкоцитах. Встановлено, що розвиток цД, індукованого стрептозотоцином, супроводжується інтенсифікацією окислювального стресу та значним зниженням життєздатності лейкоцитів порівняно з контрольною групою тварин. Введення інгібіторів PARP-1 запобігало розвитку окислювального стресу в лейкоцитах та підвищувало їх життєздатність. Виявлено зниження активності супероксиддисмутази в сироватці крові за цД. Досліджувані інгібітори PARP-1 не впливали на активність супероксиддисмутази та на рівень глюкози в крові. Одержані дані свідчать про інтенсифікацію окислювального стресу в лейкоцитах тварин з цД і здатність нікотинаміду та 1,5-ізохіноліндіолу запобігати його розвитку. к л ю ч о в і с л о в а: нікотинамід, 1,5-ізохіноліндіол, полі(ADP-рибозо)полімераза-1, лейкоцити крові, активні форми оксигену, життєздатність клітин, експериментальний цукровий діабет.

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Background. Presently, a prospective direction for the development of regenerative medicine in the world is the search for regulatory molecules and the identification of molecular targets to stimulate the body's endogenous regenerative potential. The concentrate of the deproteinized dermal layer of porcine skin (СDDLPS) is a new therapeutic agent with restorative properties, the action of which is directed on the induction of the self resources of cells. Aim. The assessment of the effect of СDDLPS on the proliferative activity of mammalian cells of different histogenesis in vitro. Materials and Methods. To determine the amino acid composition of the СDDLPS liquid chromatography and biochemical methods were used. The biological effects and mechanisms of action of the drug were investigated by cell culture and molecular biological methods. The research was carried out using stable cell lines: human keratinocytes (HaCaT cell line), porcine endothelial cells (PAE cell line), bovine kidney cells (MDBK cell line) and mouse fibroblasts (3T3A31 cell line). Results. The cells of the bovine kidney MDBK cell line were the most sensitive to the effect of the CDDLPS. Also, the obtained results suggest that, depending on the concentration, the drug not only stimulates cell proliferation by 10–30 %, but also significantly enhances biosynthetic processes in cells, in particular, protein synthesis by 20–40 %. Conclusions. CDDLPS is an effective and affordable therapeutic agent with restorative properties, the biological activity of which manifests itself in the activation of cell biosynthetic and proliferative potentials and is comparable to effects of some growth factors, in particular epidermal growth factor