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Expression of the Sod1 gene under conditions of experimental ethanol intoxication and administration of hepatoprotective drugs

https://doi.org/10.31146/1682-8658-ecg-194-10-132-137

Abstract

The aim of the study was to study the effect of hepatoprotective drugs on the expression of the Sod1 gene in rats with ethanol liver damage.

Materials and methods. Male outbred white rats were used in the experiment. Five groups of animals were formed, 14 individuals each. Distilled water was administered to rats of the 1st group (control); Group 2 — ethanol at a dose of 5 g/kg of body weight; Group 3 — ethanol and heptor at a dose of 72 mg/kg; Group 4 — ethanol and mexidol at a dose of 50 mg/kg; Group 5 — ethanol and OMU at a dose of 50 mg/kg. The drugs were administered 1 hour before the introduction of ethanol. 24 and 72 hours after the introduction of ethanol (7 individuals), the animals were decapitated and the liver was removed. The expression level of the Sod1 gene was assessed using real-time reverse transcription PCR.

Results. The fold change in Sod1 expression in rat liver after 24 h practically did not change in response to the introduction of ethanol to the animals. A tendency to a slight decrease was observed in relation to changes in the expression of Sod1 with the use of heptor and mexidol, while under the influence of OMU, the expression level increased moderately. After 72 h, the exposure to ethanol was accompanied by a slight decrease in the frequency of expression of the Sod1 gene. A similar trend was observed with respect to changes in Sod1 expression with the use of heptor, mexidol, and OMU.

Conclusion. The results obtained indicate that the introduction of both ethanol and the prophylactic use of hepatoprotective drugs did not lead to significant changes in the level of Sod1 gene expression in rat liver. Additional studies are needed to identify the mechanisms of regulation of the antioxidant system, as well as the search for drugs that affect the transcriptional activity of genes.

About the Authors

G. F. Mukhammadieva
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation

Guzel F. Mukhammadieva - Candidate of Biological Sciences, Senior researcher at the Department of Toxicology and Genetics with The Experimental Clinics for Laboratory Animals.

Stepana Kuvykina 94, Ufa, 450106.



A. B. Bakirov
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation

Akhat B. Bakirov - Doctor of Medical Sciences, Professor, Director.

Stepana Kuvykina 94, Ufa, 450106.



D. O. Karimov
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation

Denis O. Karimov - Candidate of Medical Sciences, Head of the Department of Toxicology and Genetics with The Experimental Clinics for Laboratory Animals.

Stepana Kuvykina 94, Ufa, 450106.



Ya. V. Valova
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation

Yana V. Valova - Junior researcher at the Department of Toxicology and Genetics with The Experimental Clinics for Laboratory Animals.

Stepana Kuvykina 94, Ufa, 450106.



M. M. Ziatdinova
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation

Munira M. Ziatdinova - Junior researcher at the Department of Toxicology and Genetics with The Experimental Clinics for Laboratory Animals.

Stepana Kuvykina 94, Ufa, 450106.



E. R. Kudoyarov
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation

Eldar R. Kudoyarov - Junior researcher at the Department of Toxicology and Genetics with The Experimental Clinics for Laboratory Animals.

Stepana Kuvykina 94, Ufa, 450106.



E. F. Repina
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation

Elvira F. Repina - Candidate of Medical Sciences, Senior researcher at the Department of Toxicology and Genetics with The Experimental Clinics for Laboratory Animals.

Stepana Kuvykina 94, Ufa, 450106.



T. G. Yakupova
Ufa Research Institute of Occupational Health and Human Ecology
Russian Federation

Tatyana G. Yakupova - Junior researcher at the Department of Toxicology and Genetics with The Experimental Clinics for Laboratory Animals.

Stepana Kuvykina 94, Ufa, 450106.



References

1. Zhou Y., Zheng J., Li S., et al. Alcoholic Beverage Consumption and Chronic Diseases. Int. J. Environ. Res. Public Health. 2016;13(6):522. doi: 10.3390/ijerph13060522.

2. Polunina T. E. Alcoholic liver disease. Farmateka. 2019;26(2):106-114. (In Russ.) doi: 10.18565/pharmateca.2019.2.106-114.

3. Kubiak-Tomaszewska G., Tomaszewski P., Pachecka J., et al. Molecular mechanisms of ethanol biotransformation: enzymes of oxidative and nonoxidative metabolic pathways in human. Xenobiotica. 2020;50(10):1180-1201. doi: 10.1080/00498254.2020.1761571.

4. Golovanova Ye. V. Experience of use of native hepatoprotector Heptor (ademetionine) in patients with alcoholic liver disease. Farmateka. 2010;12:82-87. (In Russ.)

5. Pozhilova E.V., Novikov V. E., Novikova A. V. Pharmacodynamics and clinical applications of preparations based on hydroxypyridine. Vestnik of the Smolensk State Medical Academy. 2013;12(3):56-66. (In Russ.)

6. Mushkin V.A., Repina E. F., Khusnutdinova N. Yu., et al. Antitoxic activity of pyrimidines (structure - activity). Occupational health and human ecology. 2018;4:117-123. (In Russ.)

7. Kawamata H., Manfredi G. Import, maturation, and function of SOD1 and its copper chaperone CCS in the mitochondrial intermembrane space. Antioxid. Redox Signal. 2010;13(9):1375-84. doi: 10.1089/ars.2010.3212.

8. Fukai T., Folz R. J., Landmesser U., Harrison D. G. Extracellular superoxide dismutase and cardiovascular disease. Cardiovasc. Res. 2002;55(2):239-49. doi: 10.1016/s0008-6363(02)00328-0.

9. Wang Y., Branicky R., Noe A., Hekimi S. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J. Cell Biol. 2018;217(6):1915-1928. doi: 10.1083/jcb.201708007.

10. Inoue M., Sato E. F., Nishikawa M., et al. Mitochondrial generation of reactive oxygen species and its role in aerobic life. Curr. Med. Chem. 2003;10(23):2495-505. doi: 10.2174/0929867033456477.

11. Lamas-Paz A., Hao F., Nelson L. J., et al. Alcoholic liver disease: Utility of animal models. World J. Gastroenterol. 2018;24(45):5063-5075. doi: 10.3748/wjg.v24.i45.5063.

12. Yang S.C., Huang C. C., Chu J. S., Chen J. R. Effects of beta-carotene on cell viability and antioxidant status of hepatocytes from chronically ethanol-fed rats. Br J Nutr. 2004;92(2):209-15. doi: 10.1079/BJN20041190.

13. Samuhasaneeto S., Thong-Ngam D., Kulaputana O., et al. Curcumin decreased oxidative stress, inhibited NF-kappaB activation, and improved liver pathology in ethanol-induced liver injury in rats. J Biomed Biotechnol. 2009;2009:981963. doi: 10.1155/2009/981963.

14. Farbiszewski R., Chwiecko M., Holownia A., Pawlow-ska D. The decrease of superoxide dismutase activity and depletion of sulfhydryl compounds in ethanol-induced liver injury. Drug Alcohol Depend. 1991;28(3):291-4. doi: 10.1016/0376-8716(91)90063-5.

15. Polavarapu R., Spitz D. R., Sim J. E., et al. Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil. Hepatology. 1998;27(5):1317-23. doi: 10.1002/hep.510270518.

16. Zhao M., Matter K., Laissue J. A., Zimmermann A. Copper/zinc and manganese superoxide dismutases in alcoholic liver disease: immunohistochemical quantitation. Histol. Histopathol. 1996;11(4):899-907.

17. Kessova I.G., Ho Y. S., Thung S., Cederbaum A. I. Alcohol-induced liver injury in mice lacking Cu, Zn-superoxide dismutase. Hepatology. 2003;38(5):1136-45. doi: 10.1053/jhep.2003.50450.

18. Wheeler M.D., Kono H., Yin M., et al. Delivery of the Cu/Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats. Gastroenterology. 2001;120(5):1241-50. doi: 10.1053/gast.2001.23253.

19. Espinosa-Diez C., Miguel V., Mennerich D., et al. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol. 2015;6:183-197. doi: 10.1016/j.redox.2015.07.008.


Review

For citations:


Mukhammadieva G.F., Bakirov A.B., Karimov D.O., Valova Ya.V., Ziatdinova M.M., Kudoyarov E.R., Repina E.F., Yakupova T.G. Expression of the Sod1 gene under conditions of experimental ethanol intoxication and administration of hepatoprotective drugs. Experimental and Clinical Gastroenterology. 2021;(10):132-137. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-194-10-132-137

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