Intensity of endoplasmic reticulum stress, autophagy, and apoptosis in the cerebral cortex of rats with chronic ethanol consumption under the influence of the complex compound of germanium with nicotinic acid

Authors

DOI:

https://doi.org/10.15587/2519-4852.2023.295491

Keywords:

apoptosis, autophagy, chronic alcohol consumption, coordination compound of germanium

Abstract

The aim of the research – to determine the level of BAX, caspase-3, GRP78, IRE1 and Beclin-1 in the cerebral cortex of rats with chronic ethanol consumption and under conditions of exposure to the germanium complex with nicotinic acid (MIGU-1).

Materials and methods. Female rats had free access to 20 % C2H5OH as the only source of fluid for 110 days. Starting from the 90th day, the animals were injected with MIGU-1 (10 mg/kg/day, IP). The expression level of BAX, caspase-3, GRP78, IRE1 and Beclin-1 in the tissue was determined by Western blot analysis.

Results. In rats with chronic ethanol consumption, the level of BAX-dimer increased by 2.06 times (p˂0.001). The introduction of MIGU-1 caused a decrease in the level of BAX-dimer by 1.42 times (p˂0.05). In rats with chronic ethanol consumption, the level of caspase-3 increased by 2.12 times (p˂0.05), cleaved caspase-3 increased by 6.37 times (p˂0.05). When MIGU-1 was administered, the level of caspase-3 decreased by 1.73 times (p˂0.05). Under the conditions of MIGU-1 administration, protein bands of cleaved caspase-3 were reduced to an undetectable level. In rats with chronic ethanol consumption, the level of GRP78 increased by 1.72 times (p˂0.05). After administration of MIGU-1, no changes in the level of GRP78 were recorded. Long-term ethanol consumption increased the levels of IRE1 by 1.74 times (p˂0.05) and p-IRE1 by 2.7 times (p˂0.001). In the presence of MIGU-1, the levels of IRE1 and p-IRE1 did not change. Under the conditions of chronic ethanol consumption, an increase in the levels of Beclin-1 by 2.33 times (p˂0.001) and p-Beclin-1 by 4.69 times (p˂0.001) was observed. Administration of MIGU-1 did not affect the level of Beclin-1, while the level of p-Beclin-1 decreased by 3.09 times (p˂0.001).

Conclusions. Long-term ethanol consumption triggers metabolic changes in the cerebral cortex, resulting in ER stress, UPR activation, autophagy, and apoptosis. Administration of MIGU-1 alleviates ER stress by selectively inhibiting specific branches of apoptosis through effects on Beclin-1 levels, suggesting an effect of MIGU-1 on neuronal survival under chronic ethanol consumption

Author Biographies

Iryna Nizhenkovska, Bogomolets National Medical University

Doctor of Medical Sciences, Professor

Department of Medicinal Chemistry and Toxicology

Olena Kuznetsova, Bogomolets National Medical University

PhD, Associate Professor

Department of Medicinal Chemistry and Toxicology

Violetta Narokha, Bogomolets National Medical University

PhD, Associate Professor

Department of Medicinal Chemistry and Toxicology

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Intensity of endoplasmic reticulume stress, autophagy, and apoptosis in the cerebral cortex of rats with chronic ethanol consumption under the influence of the complex compound of germanium with nicotinic acid

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Published

2023-12-31

How to Cite

Nizhenkovska, I., Kuznetsova, O., & Narokha, V. (2023). Intensity of endoplasmic reticulum stress, autophagy, and apoptosis in the cerebral cortex of rats with chronic ethanol consumption under the influence of the complex compound of germanium with nicotinic acid. ScienceRise: Pharmaceutical Science, (6(46), 70–78. https://doi.org/10.15587/2519-4852.2023.295491

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No. 6(46) (2023)

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Pharmaceutical Science

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Copyright (c) 2023 Iryna Nizhenkovska, Olena Kuznetsova, Violetta Narokha

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