Influence of constant lighting on the morphofunctional state and rhythmostasis of the liver of rats

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

BACKGROUND: There are evidences that light pollution, which causes melatonin deficiency and disruption of circadian rhythm, is associated with the development of malignant neoplasms of the liver, non-alcoholic fatty liver disease, biliary cirrhosis, and a number of other pathologies of this organ.

AIM: The aim of research was to study the features of chronic influence of constant lighting on lability of morphofunctional state of liver of mature Wistar rats and the structure of circadian rhythms of its parameters.

MATERIALS AND METHODS: The study was conducted on 80 rats divided into 2 groups: a control group kept under a fixed light regime (light/dark 12/12 h, lights on at 8:00 and off at 20:00), and an experimental group kept under constant lighting 24 h a day. The duration of the experiment was 3 weeks.

RESULTS: It’s established that influence of constant light led to an increase in the size of hepatocytes and a decrease in nuclear-cytoplasmic ratio, average ploidy and proportion of binuclear hepatocytes, and also to development of fatty degeneration, a decrease in the expression of Bmal1 and Clock, and an increase in the expression of per2 and p53 in hepatocytes. At the same time, there was a decrease in glycogen content in hepatocytes. Dark deprivation also caused an increase in glucose levels, AST activity, and a decrease in blood levels of total protein and albumin. Constant lighting caused a rearrangement of the circadian rhythms of the area of nuclei, the area of the hepatocyte and nuclear-cytoplasmic ratio, Bmal1, per2, Clock expression, and led to destruction of Ki67 and p53 circadian rhythms in hepatocytes. Under conditions of constant lighting, the circadian rhythms of the content of lipids and glycogen in hepatocytes, ALT activity in the blood, and the content of total and direct bilirubin were also destroyed.

CONCLUSIONS: It has been established that constant illumination causes a restructuring of the circadian rhythms of a number of studied parameters against the background of morphological and functional changes, indicating a decrease in the adaptive capacity of the liver.

About the authors

Sevil A. Grabeklis

Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry

Email: ombn.ramn@mail.ru
ORCID iD: 0009-0002-3290-3768

Engineer of the Laboratory of Chemistry of Proteolytic Enzymes

Russian Federation, Moscow

Liudmila M. Mikhaleva

A.P. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery

Email: mikhalevalm@yandex.ru
ORCID iD: 0000-0003-2052-914X
Scopus Author ID: 57213652796

MD, Dr. Sci. (Med.), Corresponding Member of the Russian Academy of Sciences, Director

Russian Federation, Moscow

Maria A. Kozlova

A.P. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery

Email: ma.kozlova2021@outlook.com
ORCID iD: 0000-0001-6251-2560
Scopus Author ID: 55976515700

Dr. Sci. (Biol.), Research Associate of Laboratory of Cell Pathology

Russian Federation, Moscow

David A. Areshidze

A.P. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery

Author for correspondence.
Email: labcelpat@mail.ru
ORCID iD: 0000-0003-3006-6281
SPIN-code: 4348-6781
Scopus Author ID: 55929152900
ResearcherId: G-8387-2014

Dr. Sci. (Biol.), Head of Laboratory of Cell Pathology

Russian Federation, Moscow

Alexander M. Dygai

Research Institute of General Pathology and Pathophysiology

Email: ombn.ramn@mail.ru
ORCID iD: 0000-0001-6286-5315
Scopus Author ID: 56248430500
ResearcherId: A-4528-2015

MD, Dr. Sci. (Med.), Academician of the Russian Academy of Sciences, Chief Research Associate

Russian Federation, Moscow

References

  1. Rapoport SI, Chibisov SM, Breus TK, et al. Khronobiologiya i khronomeditsina: istoriya i perspektivy. Moscow; 2018. P. 9–38. (In Russ.)
  2. Forger DB. Biological clocks, rhythms, and oscillations: The theory of biological timekeeping. Cambridge (MA): MIT Press; 2017.
  3. Chibisov SM, Dement’ev MV, Blagonravov ML, et al. Korrelyatsionno-regressionnyy analiz desinkhronoza. Proceedings of the conference “Novyye tekhnolo-gii v rekreatsii zdorov’ya naseleniya”. 2018. P. 5–10. (In Russ.)
  4. McKenna H, van der Horst GTJ, Reiss I, Martin D. Clinical chronobiology: a timely consideration in critical care medicine. Crit Care. 2018;22(1):124. doi: 10.1186/s13054-018-2041-x
  5. Walker WH II, Bumgarner JR, Walton JC, et al. Light pollution and cancer. Int J Mol Sci. 2020;21(24):9360. doi: 10.3390/ijms21249360
  6. Panda S. Circadian physiology of metabolism. Science. 2016;354(6315):1008–1015. doi: 10.1126/science.aah4967
  7. Zimmet P, Alberti KGMM, Stern N, et al. The circadian syndrome: is the metabolic syndrome and much more! J Intern Med. 2019;286(2):181–191. doi: 10.1111/joim.12924
  8. Mure LS, Le HD, Benegiamo G, et al. Diurnal transcriptome atlas of a primate across major neural and peripheral tissues. Science. 2018;359(6381):eaao0318. doi: 10.1126/science.aao0318
  9. Foster RG, Roenneberg T. Human responses to the geophysical daily, annual and lunar cycles. Curr Biol. 2008;18(17):R784–R794. doi: 10.1016/j.cub.2008.07.003
  10. Michel S, Meijer JH. From clock to functional pacemaker. Eur J Neurosci. 2020;51(1):482–493. doi: 10.1111/ejn.14388
  11. Reppert SM, Weaver DR. Coordination of circadian timing in mammals. Nature. 2002;418(6901):935–941. doi: 10.1038/nature00965
  12. Verlande A, Masri S. Circadian clocks and cancer: Timekeeping governs cellular metabolism. Trends Endocrinol Metab. 2019;30(7):445–458. doi: 10.1016/j.tem.2019.05.001
  13. Anisimov VN. Light desynchronosis and health. Light and Engineering. 2019;27(3):14–25. doi: 10.33383/2018-120
  14. Leng Y, Musiek ES, Hu K, et al. Association between circadian rhythms and neurodegenerative diseases. Lancet Neurol. 2019;18(3):307–318. doi: 10.1016/S1474-4422(18)30461-7
  15. Rumanova VS, Okuliarova M, Zeman M. Differential effects of constant light and dim light at night on the circadian control of metabolism and behavior. Int J Mol Sci. 2020;21(15):5478. doi: 10.3390/ijms21155478
  16. Bumgarner JR, Nelson RJ. Light at night and disrupted circadian rhythms alter physiology and behavior. Integr Comp Biol. 2021;61(3):1160–1169. doi: 10.1093/icb/icab017
  17. Fárková E, Schneider J, Šmotek M, et al. Weight loss in conservative treatment of obesity in women is associated with physical activity and circadian phenotype: a longitudinal observational study. Biopsychosoc Med. 2019;13:24. doi: 10.1186/s13030-019-0163-2
  18. Stevens RG, Davis S, Mirick DK, et al. Alcohol consumption and urinary concentration of 6-sulfatoxymelatonin in healthy women. Epidemiology. 2000;11(6):660–665. doi: 10.1097/00001648-200011000-00008
  19. Audebrand A, Désaubry L, Nebigil CG. Targeting GPCRs against cardiotoxicity induced by anticancer treatments. Front Cardiovasc Med. 2020;6:194. doi: 10.3389/fcvm.2019.00194
  20. Han Y, Chen L, Baiocchi L, et al. Circadian rhythm and melatonin in liver carcinogenesis: updates on current findings. Crit Rev Oncog. 2021;26(3):69–85. doi: 10.1615/CritRevOncog.2021039881
  21. Poggiogalle E, Jamshed H, Peterson CM. Circadian regulation of glucose, lipid, and energy metabolism in humans. Metabolism. 2018;84:11–27. doi: 10.1016/j.metabol.2017.11.017
  22. Mota MC, Silva CM, Balieiro LCT, et al. Social jetlag and metabolic control in non-communicable chronic diseases: a study addressing different obesity statuses. Sci Rep. 2017;7(1):6358. doi: 10.1038/s41598-017-06723-w
  23. Yalçin M, El-Athman R, Ouk K, et al. Analysis of the circadian regulation of cancer hallmarks by a cross-platform study of colorectal cancer time-series data reveals an association with genes involved in Huntington’s disease. Cancers (Basel). 2020;12(4):963. doi: 10.3390/cancers12040963
  24. Shurkevich NP, Vetoshkin AS, Gapon LI, et al. Prognostic value of blood pressure circadian rhythm disturbances in normotensive shift workers of the arctic polar region. Arterial Hypertension. 2017;23(1):36–46. (In Russ.) doi: 10.18705/1607-419X-2017-23-1-36-46
  25. Ul’yanovskaya SA. Vliyaniye fotoperiodiki Severa na organizm cheloveka (obzor literatury). Proceedings of the International Scientific and Practical Conference “Borodinskiye chteniya”, dedicated to the 90th anniversary of Academician of the Russian Academy of Sciences Yuri I. Borodin. Novosibirsk; 2019. P. 346–352. (In Russ.)
  26. Wei Y, Neuveut C, Tiollais P, Buendia MA. Molecular biology of the hepatitis B virus and role of the X gene. Pathol Biol (Paris). 2010;58(4):267–272. doi: 10.1016/j.patbio.2010.03.005
  27. Masri S, Sassone-Corsi P. The emerging link between cancer, metabolism, and circadian rhythms. Nat Med. 2018;24(12):1795–1803. doi: 10.1038/s41591-018-0271-8
  28. Avtandilov GG. Diagnosticheskaya meditsinskaya ploidometriya. Moscow: Meditsina; 2009. 192 p. (In Russ.)
  29. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–675. doi: 10.1038/nmeth.2089
  30. Ir’yanov YuM, Silant’yeva TA, Gorbach YeN, Ir’yanova TYu. A portable device-and-program complex and the possibilities of itsuse for histological studies. Geniy ortopedii. 2004;(3):96–98. (In Russ.)
  31. Rubin Grandis J, Melhem MF, Barnes EL, Tweardy DJ. Quantitative immunohistochemical analysis of transforming growth factor-alpha and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck. Cancer. 1996;78(6):1284–1292. doi: 10.1002/(SICI)1097-0142(19960915)78:6<1284::AID-CNCR17>3.0.CO;2-X
  32. Lazzeri E, Angelotti ML, Conte C, et al. Surviving acute organ failure: cell polyploidization and progenitor proliferation. Trends Mol Med. 2019;25(5):366–381. doi: 10.1016/j.molmed.2019.02.006
  33. Nagy P, Teramoto T, Factor VM, et al. Reconstitution of liver mass via cellular hypertrophy in the rat. Hepatology. 2001;33(2):339–345. doi: 10.1053/jhep.2001.21326
  34. Zhou D, Wang Y, Chen L, et al. Evolving roles of circadian rhythms in liver homeostasis and pathology. Oncotarget. 2016;7(8):8625–8639. doi: 10.18632/oncotarget.7065
  35. Miyaoka Y, Ebato K, Kato H, et al. Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration. Curr Biol. 2012;22(13):1166–1175. doi: 10.1016/j.cub.2012.05.016
  36. Yel’chaninov AV, Fatkhudinov TKh. Regeneratsiya pecheni mlekopitayushchikh: Mezhkletochnyye vzaimodeystviya. Moscow: Nauka; 2020. 126 p. (In Russ.)
  37. Chojnacki C, Walecka-Kapica E, Romanowski M, et al. Protective role of melatonin in liver damage. Curr Pharm Des. 2014;20(30):4828–4833. doi: 10.2174/1381612819666131119102155
  38. Esteban-Zubero E, Alatorre-Jiménez MA, López-Pingarrón L, et al. Melatonin’s role in preventing toxin-related and sepsis-mediated hepatic damage: a review. Pharmacol Res. 2016;105:108–120. doi: 10.1016/j.phrs.2016.01.018
  39. Yatsuji S, Hashimoto E, Tobari M, et al. Influence of age and gender in Japanese patients with non-alcoholic steatohepatitis. Hepatol Res. 2007;37(12):1034–1043. doi: 10.1111/j.1872-034X.2007.00156.x
  40. Hajam YA, Rai S. Melatonin and insulin modulates the cellular biochemistry, histoarchitecture and receptor expression during hepatic injury in diabetic rats. Life Sci. 2019;239:117046. doi: 10.1016/j.lfs.2019.117046
  41. Corona-Pérez A, Díaz-Muñoz M, Rodríguez IS, et al. High sucrose intake ameliorates the accumulation of hepatic triacylglycerol promoted by restraint stress in young rats. Lipids. 2015;50(11):1103–1113. doi: 10.1007/s11745-015-4066-0
  42. Schott MB, Rasineni K, Weller SG, et al. β-Adrenergic induction of lipolysis in hepatocytes is inhibited by ethanol exposure. J Biol Chem. 2017;292(28):11815–11828. doi: 10.1074/jbc.M117.777748
  43. Panasiuk A, Dzieciol J, Panasiuk B, Prokopowicz D. Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease. World J Gastroenterol. 2006;12(38):6198–6202. doi: 10.3748/wjg.v12.i38.6198
  44. Fu L, Pelicano H, Liu J, et al. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell. 2002;111(1):41–50. doi: 10.1016/s0092-8674(02)00961-3
  45. Hardeland R. Melatonin and the pathologies of weakened or dysregulated circadian oscilla sis. Oncotarget. 2017;8(57):96476–96477. doi: 10.18632/oncotarget.22255
  46. Scheving LA. Biological clocks and the digestive system. Gastroenterology. 2000;119(2):536–549. doi: 10.1053/gast.2000.9305
  47. Zatloukal K, Denk H, Spurej G, Hutter H. Modulation of protein composition of nuclear lamina. Reduction of lamins B1 and B2 in livers of griseofulvin-treated mice. Lab Invest. 1992;66(5):589–597.
  48. Chua EC, Shui G, Lee IT, et al. Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans. Proc Natl Acad Sci USA. 2013;110(35):14468–14473. doi: 10.1073/pnas.1222647110
  49. Bailey SM. Emerging role of circadian clock disruption in alcohol-induced liver disease. Am J Physiol Gastrointest Liver Physiol. 2018;315(3):G364–G373. doi: 10.1152/ajpgi.00010.2018
  50. DePietro RH, Knutson KL, Spampinato L, et al. Association between inpatient sleep loss and hyperglycemia of hospitalization. Diabetes Care. 2017;40(2):188–193. doi: 10.2337/dc16-1683

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Liver of rats of the control group. Нematoxylin and eosin: a — ×200, b — ×400

Download (310KB)
Indexing metadata
3. Fig. 2. Liver of rats of the experimental group: a — hematoxylin and eosin, ×400; b — staining with Sudan III with additional staining with hematoxylin, ×400

Download (285KB)
Indexing metadata

Copyright (c) 2023 Eco-Vector



Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».