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Registration Number

0225U003486, (0123U101110) , R & D reports

Title

The role of the thiol-disulfide system in the implementation of neurodestruction/neuroprotection mechanisms and the development of pharmacological modulation pathways after prenatal hypoxia

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Дослідження порушень у головному мозку після ПГ і після ПГ на тлі депривації тіол-дисульфідної системи (глутатіонова ланка)

Head

Belenichev Ihor Fedorovych, Доктор біологічних наук

Registration Date

02-07-2025

Organization

Zaporizhzhya State Medical University

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Еxperimentally substantiate the use of modulators of thiol-disulfide system (glutathione, glutaredoxine, and derivatives of selenium, tiazotate, and cysteine), as well as heat shock factor 1 (HSF-1) in the management of consequences of prenatal CNS hypoxia on the basis of experimental data revealing the role of the thiol-disulfide system in the interruption of NO-; IL-1b; ROS-dependent mechanisms of neurodestruction and excitotoxicity and SH/HSP70 – mediated regulation mechanisms of endogenous neuroprotection.

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In the work involving modern biochemical, molecular, immunohistochemical research methods, as well as PCR, we have established for the first time that intrauterine hypoxia leads to suppression of eNOS mRNA expression and eNOS activity and a parallel increase in iNOS mRNA expression and iNOS activity in the myocardium and brain of the offspring at 1 and 2 months of life. It was also found that intrauterine hypoxia led to a decrease in NO bioavailability and activation of nitrosative stress in the myocardium of the offspring at 1 and 2 months of life. We obtained convincing results that simulated PG leads to persistent disorders of the cardiovascular system in offspring (1 and 2 month old rats). In the target organs of rats that underwent PG, an increase in the level of the endothelial dysfunction marker cEPCR was detected against the background of a decrease in the levels of Tie-2 and VEGF-B, which perform protective functions, as well as antioxidant deficiency. The developed 1% gel with Angiolin for neuroprotection meets all the requirements for safety and harmlessness of dosage forms of this group - low toxicity, lack of local irritant and allergic effects. It was found that Thiotriazolin and Angiolin had a positive effect on the synthesis and bioavailability of NO and limited nitrosative stress in the myocardium of newborns after PG. It was found that Angiolin and Cerebrocurin improved the morpho-functional parameters of neurons in the CA1 zone of the hippocampus. Angiolin and Cerebrocurin increased survival and improved cognitive and memory functions of 2-month-old rats after PG. The obtained results are an experimental justification for further study of the studied drugs, especially Angiolin and Cerebrocurin, as promising neuroprotective agents in the complex therapy of CNS lesions after intrauterine hypoxia in newborns.

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Aliieva Olena Н.
Berest Halyna H.
Honcharov Oleksii V.
Dmytriieva Oksana O.
Kozhem'iaka Maksym O.
Kuchkovskyi Oleh M.
Makieieva Liudmyla V.
Popazova Olena O.
Ryzhenko Viktor P.
Salnikov Valerii I.
Samura Iryna B.
Skoryna Dmytro Yu.

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2025-07-02