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DOI 10.34014/2227-1848-2023-3-151-166

INFLUENCE OF COMBINED EFFECT OF CONSTANT ILLUMINATION AND CHRONIC ALCOHOL INTOXICATION ON HEPATOCYTE ULTRASTRUCTURE IN MALE AND FEMALE WISTAR RATS

D.A. Areshidze, L.M. Mikhaleva, L.V. Kakturskiy, M.V. Kondashevskaya, M.A. Kozlova, V.P. Chernikov

Russian Scientific Centre for Surgery named after Academician B.V. Petrovsky, Moscow, Russia

 

Light pollution causes melatonin deficiency and circadian rhythm disruption. Thus, it is associated with hepatopathy. Circadian rhythm disruption increases liver damage from alcohol and the severity of alcoholism.

The aim of the study was to examine the combined effect of constant illumination and chronic alcohol intoxication (CAI) on hepatocyte ultrastructure in male and female rats.

Materials and Methods. The study was carried out on 120 male and 80 female Wistar outbred rats aged
6 months. The experiment lasted 3 weeks. Differences in morphological patterns of hepatocyte ultrastructure were visually assessed. The percentage of hepatocytes containing lipid vacuoles was calculated.

Results. Constant illumination and chronic alcohol intoxication caused allostasis. Hepatocyte edema, mitochondria swelling, karyopyknosis, fatty degeneration, and hepatocyte death were detected in the liver cells of male and female rats. The above-mentioned pathological changes were less severe in females. Moreover, collagen layers did not proliferate into the liver tissues in female rats. So, we can conclude that the combined effect of constant illumination and CAI do not lead to inflammatory changes and architectural distortion in the liver of female rats. Taking into account the morphological picture of the liver of male and female rats and a number of biochemical parameters that describe its functional state, the obtained data on gender differences in the hepatocyte ultrastructure in rats exposed to CAI and constant illumination allow us to report that hepatocyte adaptation to stress is more successful in female rats than in male ones.

Key words: hepatocyte response of female and male Wistar rats to combined effect of constant illumination and alcohol intoxication, melatonin, electron microscopy.

 

Conflict of interest. The authors declare no conflict of interest.

Author contributions

Research concept and design: Areshidze D.A., Kakturskiy L.V., Kondashevskaya M.V.

Literature search, participation in the research study, data processing: Areshidze D.A., Kozlova M.A., Chernikov V.P.

Data analysis and interpretation: Areshidze D.A., Kakturskiy L.V., Mikhaleva L.M., Chernikov V.P., Kozlova M.A., Kondashevskaya M.V.

Text writing and editing: Areshidze D.A., Kakturskiy L.V., Mikhaleva L.M., Chernikov V.P.,

Kondashevskaya M.V., Kozlova M.A.

 

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Received May 29, 2023; accepted June 18, 2023.

 

Information about the authors

Areshidze David Aleksandrovich, Candidate of Sciences (Biology), Head of the Laboratory of Cell Pathology, Avtsyn Research Institute of Human Morphology, Russian Scientific Centre for Surgery named after Academician B.V. Petrovsky. 117418, Russia, Moscow, Tsyurupy St., 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0003-3006-6281.

Mikhaleva Lyudmila Mikhaylovna, Corresponding Member, Russian Academy of Sciences, Director of Avtsyn Research Institute of Human Morphology, Russian Scientific Centre for Surgery named after Academician B.V. Petrovsky. 117418, Russia, Moscow, Tsyurupy St., 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0003-2052-914X.

Kakturskiy Lev Vladimirovich, Corresponding Member, Russian Academy of Sciences, Scientific Director of Avtsyn Research Institute of Human Morphology, Russian Scientific Centre for Surgery named after Academician B.V. Petrovsky. 117418, Russia, Moscow, Tsyurupy St., 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0001-7896-2080.

Kondashevskaya Marina Vladislavovna, Doctor of Sciences (Biology), Chief Researcher, Avtsyn Research Institute of Human Morphology, Russian Scientific Centre for Surgery named after Academician B.V. Petrovsky. 117418, Russia, Moscow, Tsyurupy St., 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-8096-5974.

Kozlova Mariya Aleksandrovna, Candidate of Sciences (Biology), Researcher, Laboratory of Cell Pathology, Avtsyn Research Institute of Human Morphology, Russian Scientific Centre for Surgery named after Academician B.V. Petrovsky. 117418, Russia, Moscow, Tsyurupy St., 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0001-6251-2560.

Chernikov Valeriy Petrovich, Candidate of Sciences (Medicine), Leading Researcher, Laboratory of Cell Pathology, Avtsyn Research Institute of Human Morphology, Russian Scientific Centre for Surgery named after Academician B.V. Petrovsky. 117418, Russia, Moscow, Tsyurupy St., 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-3253-6729.

 

For citation

Areshidze D.A., Mikhaleva L.M., Kakturskiy L.V., Kondashevskaya M.V., Kozlova M.A., Chernikov V.P. Vliyanie sovmestnogo deystviya postoyannogo osveshcheniya i khronicheskoy alkogol'noy intoksikatsii na ul'trastrukturu gepatotsitov samtsov i samok krys «Vistar» [Influence of combined effect of constant illumination and chronic alcohol intoxication on hepatocyte ultrastructure in male and female Wistar rats]. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2023; 3: 151–166. DOI: 10.34014/2227-1848-2023-3-151-166 (in Russian).

 

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УДК 616-091.8

DOI 10.34014/2227-1848-2023-3-151-166

ВЛИЯНИЕ СОВМЕСТНОГО ДЕЙСТВИЯ ПОСТОЯННОГО ОСВЕЩЕНИЯ И ХРОНИЧЕСКОЙ АЛКОГОЛЬНОЙ ИНТОКСИКАЦИИ НА УЛЬТРАСТРУКТУРУ ГЕПАТОЦИТОВ САМЦОВ И САМОК КРЫС «ВИСТАР»

Д.А. Арешидзе, Л.М. Михалёва, Л.В. Кактурский, М.В. Кондашевская, М.А. Козлова, В.П. Черников

ФГБНУ «Российский научный центр хирургии им. академика Б.В. Петровского», г. Москва, Россия

 

Световое загрязнение, вызывающее дефицит мелатонина и нарушение циркадианной ритмичности, ассоциировано с развитием ряда патологий печени. Рассогласование суточной ритмики приводит к повышению восприимчивости печени к вызываемым алкоголем повреждениям, усилению тяжести алкогольной болезни.

Целью исследования было изучение сочетанного действия постоянного освещения и хронической алкогольной интоксикации (ХАИ) на ультраструктуру гепатоцитов крыс обоих полов.

Материалы и методы. Исследование проведено на 120 самцах и 80 самках крыс аутбредного стока «Вистар» в возрасте 6 мес. Длительность эксперимента составляла 3 нед. Визуально оценивали различия в морфологической картине ультраструктур гепатоцитов, количественно определяли процент гепатоцитов, содержащих липидные вакуоли.

Результаты. Постоянное освещение и хроническая алкогольная интоксикация вызывали формирование состояния аллостаза. В клетках печени крыс обоих полов были выявлены отек гепатоцитов, набухание митохондрий, сморщивание ядра, развитие жировой дистрофии, гибель гепатоцитов. Половые различия заключались в меньшей выраженности указанных патологических изменений
у самок. В сочетании с отсутствием у крыс женского пола разрастания коллагеновых прослоек в тканях печени перечисленные данные свидетельствуют о том, что в печени самок, в отличие от печени самцов, сочетанное воздействие постоянного освещения и ХАИ не приводит к развитию изменений воспалительного характера и нарушению архитектоники. С учетом ранее охарактеризованной нами морфологической картины печени крыс обоих полов и ряда биохимических параметров, описывающих ее функциональное состояние, полученные данные о межполовых различиях в ультраструктурных характеристиках гепатоцитов крыс, подверженных воздействию ХАИ и постоянного освещения, позволяют нам высказать утверждение о более успешном протекании адаптации гепатоцитов к стрессорным условиям у самок крыс, нежели у самцов.

Ключевые слова: реакция гепатоцитов самок и самцов крыс «Вистар» на сочетанное действие постоянного освещения и потребление алкоголя, мелатонин, электронная микроскопия.

 

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов

Концепция и дизайн исследования: Арешидзе Д.А., Кактурский Л.В., Кондашевская М.В.

Литературный поиск, участие в исследовании, обработка материала: Арешидзе Д.А., Козлова М.А., Черников В.П.

Анализ и интерпретация данных: Арешидзе Д.А., Кактурский Л.В., Михалева Л.М., Черников В.П., Козлова М.А., Кондашевская М.В.

Написание и редактирование текста: Арешидзе Д.А., Кактурский Л.В., Михалева Л.М., Черников В.П., Кондашевская М.В., Козлова М.А. 

 

Литература

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  3. Gubin D.G., Kolomeichuk S.N., Weinert D. Circadian clock precision, health, and longevity. J. Chronomed. 2021; 23 (1): 3–15.

  4. Bumgarner J.R., Nelson R.J. Light at Night and Disrupted Circadian Rhythms Alter Physiology and Behavior. Integr Comp Biol. 2021; 61 (3): 1160–1169.

  5. Fárková E., Schneider J., Šmotek M., Bakštein E., Herlesová J., Kopřivová J., Fried M. Weight loss in conservative treatment of obesity in women is associated with physical activity and circadian phenotype: A longitudinal observational study. BioPsychoSocial Medicine. 2019; 13: 1–10.

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  8. Talib W.H., Alsayed A.R., Abuawad A., Daoud S., Mahmod A.I. Melatonin in cancer treatment: current knowledge and future opportunities. Molecules. 2021; 26 (9): 2506.

  9. Han Y., Chen L., Baiocchi L., Ceci L., Glaser S., Francis H., Alpini G., Kennedy L. Circadian Rhythm and Melatonin in Liver Carcinogenesis: Updates on Current Findings. Crit Rev Oncog. 2021; 26 (3): 69–85.

  10. Nelson R.J., Chbeir S. Dark matters: effects of light at night on metabolism. Proc Nutr Soc. 2018; 77 (3): 223–229.

  11. Walker W.H. 2nd, Bumgarner J.R., Walton J.C., Liu J.A., Meléndez-Fernández O.H., Nelson R.J., DeVries A.C. Light Pollution and Cancer. Int J Mol Sci. 2020; 21 (24): 9360.

  12. Kramer A., Lange T., Spies C., Finger A.M., Berg D., Oster H. Foundations of circadian medicine. PLoS biology. 2022; 20 (3): e3001567.

  13. Gonzalez D., Justin H., Reiss S., Faulkner J., Mahoney H., Yunus A., Gulick D. Circadian rhythm shifts and alcohol access in adolescence synergistically increase alcohol preference and intake in adulthood in male C57BL/6 mice. Behavioural Brain Research. 2023; 438: 114216.

  14. Karlsson H., Persson E., Perini I., Yngve A., Heilig M., Tinghög G. Acute effects of alcohol on social and personal decision making. Neuropsychopharmacology. 2022; 47 (4): 824–831.

  15. Tamura E.K., Oliveira-Silva K.S., Ferreira-Moraes F.A., Marinho E.A., Guerrero-Vargas N.N. Circadian rhythms and substance use disorders: A bidirectional relationship. Pharmacology Biochemistry and Behavior. 2021; 201: 173105.

  16. Katary M., Abdel-Rahman A.A. Alcohol suppresses cardiovascular diurnal variations in male normotensive rats: Role of reduced PER2 expression and CYP2E1 hyperactivity in the heart. Alcohol. 2020; 89: 27–36.

  17. Tice A.L., Laudato J.A., Fadool D.A., Gordon B.S., Steiner J.L. Acute binge alcohol alters whole body metabolism and the time-dependent expression of skeletal muscle-specific metabolic markers for multiple days in mice. American Journal of Physiology-Endocrinology and Metabolism. 2022; 323 (3): E215–E230.

  18. Kurhaluk N. Alcohol and melatonin. Chronobiol Int. 2021; 38 (6): 785–800.

  19. Costa R., Mangini C., Domenie E.D., Zarantonello L., Montagnese S. Circadian rhythms and the liver. Liver International. 2023; 43 (3): 534–545.

  20. Nicolaides N.C., Chrousos G.P. Sex differences in circadian endocrine rhythms: Clinical implications. Eur J Neurosci. 2020; 52 (1): 2575–2585.

  21. Walton J.C., Bumgarner J.R., Nelson R.J. Sex Differences in Circadian Rhythms. Cold Spring Harb Perspect Biol. 2022; 14 (7): a039107.

  22. Layton A.T. His and her mathematical models of physiological systems. Mathematical Biosciences. 2021; 338: 108642.

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Поступила в редакцию 29.05.2023; принята 18.06.2023.

 

Авторский коллектив

Арешидзе Давид Александрович – кандидат биологических наук, заведующий лабораторией патологии клетки Научно-исследовательского института морфологии человека им. академика А.П. Авцына, ФГБНУ «Российский научный центр хирургии им. академика Б.В. Петровского». 117418, Россия, г. Москва, ул. Цюрупы, 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0003-3006-6281.

Михалева Людмила Михайловна – член-корреспондент Российской академии наук, директор Научно-исследовательского института морфологии человека им. академика А.П. Авцына, ФГБНУ «Российский научный центр хирургии им. академика Б.В. Петровского». 117418, Россия, г. Москва, ул. Цюрупы, 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0003-2052-914X.

Кактурский Лев Владимирович – член-корреспондент Российской академии наук, научный руководитель Научно-исследовательского института морфологии человека им. академика А.П. Авцына, ФГБНУ «Российский научный центр хирургии им. академика Б.В. Петровского». 117418, Россия,
г. Москва, ул. Цюрупы, 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0001-7896-2080.

Кондашевская Марина Владиславовна – доктор биологических наук, главный научный сотрудник лаборатории патологии клетки Научно-исследовательского института морфологии человека им. академика А.П. Авцына, ФГБНУ «Российский научный центр хирургии им. академика Б.В. Петровского». 117418, Россия, г. Москва, ул. Цюрупы, 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-8096-5974.

Козлова Мария Александровна – кандидат биологических наук, научный сотрудник лаборатории патологии клетки Научно-исследовательского института морфологии человека им. академика А.П. Авцына, ФГБНУ «Российский научный центр хирургии им. академика Б.В. Петровского». 117418, Россия, г. Москва, ул. Цюрупы, 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0001-6251-2560.

Черников Валерий Петрович – кандидат медицинских наук, ведущий научный сотрудник лаборатории патологии клетки Научно-исследовательского института морфологии человека им. академика А.П. Авцына, ФГБНУ «Российский научный центр хирургии им. академика Б.В. Петровского». 117418, Россия, г. Москва, ул. Цюрупы, 3; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-3253-6729.

 

Образец цитирования

Арешидзе Д.А., Михалёва Л.М., Кактурский Л.В., Кондашевская М.В., Козлова М.А., Черников В.П. Влияние совместного действия постоянного освещения и хронической алкогольной интоксикации на ультраструктуру гепатоцитов самцов и самок крыс «Вистар». Ульяновский медико-биологический журнал. 2023; 3: 151–166. DOI: 10.34014/2227-1848-2023-3-151-166.