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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Cell and Tissue Biology</journal-id><journal-title-group><journal-title xml:lang="en">Cell and Tissue Biology</journal-title><trans-title-group xml:lang="ru"><trans-title>Цитология</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0041-3771</issn><issn publication-format="electronic">3034-6061</issn><publisher><publisher-name xml:lang="en">The Russian Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">682171</article-id><article-id pub-id-type="doi">10.31857/S0041377125010031</article-id><article-id pub-id-type="edn">DEYARN</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Статьи</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Redox status and accumulation of autophagosomes in the liver of mouse under the action of lithium chloride</article-title><trans-title-group xml:lang="ru"><trans-title>Редокс-состояние и накопление аутофагосом в печени мыши при действии хлорида лития</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Dmitrieva</surname><given-names>S. А.</given-names></name><name xml:lang="ru"><surname>Дмитриева</surname><given-names>С. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Kazan Institute of Biochemistry and Biophysics</p></bio><bio xml:lang="ru"><p>Казанский институт биохимии и биофизики<italic> </italic></p></bio><email>s_dmitrieva@list.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Ponomareva</surname><given-names>A. A.</given-names></name><name xml:lang="ru"><surname>Пономарева</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Kazan Institute of Biochemistry and Biophysics</p></bio><bio xml:lang="ru"><p>Казанский институт биохимии и биофизики</p></bio><email>s_dmitrieva@list.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">FRC Kazan Scientific Center, Russian Academy of Sciences</institution></aff><aff><institution xml:lang="ru">Федеральный исследовательский центр «Казанский научный центр Российской академии наук»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2025-03-23" publication-format="electronic"><day>23</day><month>03</month><year>2025</year></pub-date><volume>67</volume><issue>1</issue><fpage>30</fpage><lpage>41</lpage><history><date date-type="received" iso-8601-date="2025-06-03"><day>03</day><month>06</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Russian Academy of Sciences</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Российская академия наук</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Russian Academy of Sciences</copyright-holder><copyright-holder xml:lang="ru">Российская академия наук</copyright-holder></permissions><self-uri xlink:href="https://vietnamjournal.ru/0041-3771/article/view/682171">https://vietnamjournal.ru/0041-3771/article/view/682171</self-uri><abstract xml:lang="en"><p>Activation of autophagy is considered one of the promising strategies for the treatment and prevention of various non-infectious liver diseases. In this work, we assessed the changes in redox status and autophagy activation in liver tissues in vivo under the action of lithium chloride. It was shown that lithium chloride leads to the accumulation of autophagosomes in liver cells under normal conditions. This process is accompanied by a slight increase in the activity of several antioxidant enzymes. Toxic effects on the liver and the development of oxidative stress with 3-day use of LiCl were not detected. Significant rearrangements in the ultrastructure of the endoplasmic reticulum were observed, which can play a signaling role and participate in the initiation of autophagy. Thus, oral application of lithium chloride can be used as an effective modulator of the autophagy process in liver tissues.</p></abstract><trans-abstract xml:lang="ru"><p>Активация аутофагии считается одной из перспективных стратегией лечения и профилактики разнообразных неинфекционных заболеваний печени. В работе проведена оценка изменения редокс-состояния и активации аутофагии в тканях печени в условиях <italic>in vivo</italic> при действии хлористого лития (LiCl) в течение трех суток. Использовали просвечивающую электронную микроскопию для оценки образования аутофагических вакуолей в гепатоцитах печени мыши и ряд биохимических методов для определения в крови или печени активности ферментов, содержания глюкозы, пероксида водорода, уровня окислительной модификации белков и перекисного окисления липидов. Показано, что пероральное применение различных концентраций LiCl приводит к накоплению аутофагосом в клетках печени и небольшому усилению активности ряда антиоксидантных ферментов. Наблюдали значимые перестройки в ультраструктуре эндоплазматического ретикулума, которые могут играть сигнальную роль и участвовать в запуске аутофагии. Токсического действия на печень и развития окислительного стресса при применении LiCl в течение трех суток не обнаружено. Пероральное применение LiCl может использоваться в качестве эффективного модулятора процесса аутофагии в тканях печени.</p></trans-abstract><kwd-group xml:lang="en"><kwd>liver</kwd><kwd>autophagy</kwd><kwd>lithium chloride</kwd><kwd>endoplasmic reticulum</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>печень</kwd><kwd>аутофагия</kwd><kwd>хлорид лития</kwd><kwd>эндоплазматический ретикулум</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Российский научный фонд</institution></institution-wrap><institution-wrap><institution xml:lang="en">Russian Science Foundation</institution></institution-wrap></funding-source><award-id>24-25-20086</award-id></award-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Академия наук республики Татарстан</institution></institution-wrap><institution-wrap><institution xml:lang="en">Academy of Sciences of the Republic of Tatarstan</institution></institution-wrap></funding-source><award-id>24-25-20086</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Бгатова Н. П., Гаврилова Ю. С., Лыков А. П., Соловьева А. О., Макарова В. В., Бородин Ю. И., Коненков В. И. 2017. Апоптоз и аутофагия в клетках гепатокарциномы, индуцированные различными формами солей лития. Цитология. T. 59. № 3. С. 178. (Bgatova N. P., Gavrilova Y. S., Lykov A. P., Solovieva A. O., Makarova V. V., Borodin Y. I., Konenkov V. I. 2017. Apoptosis and autophagy in hepatocarcinoma cells induced by different forms of lithium salts. Tsitologiya. V. 59. № 3. P. 178.)</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Aebi H. 1984. Catalase in vitro. Methods Enzymol. V. 105. P. 121. https://doi.org/10.1016/s0076-6879(84)05016-3</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Ajoolabady A., Kaplowitz N., Lebeaupin C., Kroemer G., Kaufman R. J., Malhi H., Ren J. 2023. Endoplasmic reticulum stress in liver diseases. Hepatology. V. 77. P. 619. https://doi.org/10.1002/hep.32562</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Bortolozzi A., Fico G., Berk M., Solmi M., Fornaro M., Quevedo J., Zarate C. A. Jr., Kessing L. V., Vieta E., Carvalho A. F. 2024. New advances in the pharmacology and toxicology of lithium: a neurobiologically oriented overview. Pharmacol. Rev. V. 76. P. 323. https://doi.org/10.1124/pharmrev.120.000007</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Colombo G., Clerici M., Garavaglia M. E., Giustarini D., Rossi R., Milzani A., Dalle-Donne I. 2016. A step-by-step protocol for assaying protein carbonylation in biological samples. J. Chromatogr. B. Anal. Technol. Life Sci. V. 1019. P. 178. https://doi.org/10.1016/j.jchromb.2015.11.052</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Costa A. J., Erustes A. G., Sinigaglia R., Girardi C. E.N., Pereira G. J.S, Ureshino R. P., Smaili S. S. 2021. Lack of autophagy induction by lithium decreases neuroprotective effects in the striatum of aged rats. Pharmaceutics. V. 13. P. 135. https://doi.org/10.3390/pharmaceutics13020135</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Cribb A. E., Leeder J. S., Spielberg S. P. 1989. Use of a microplate reader in an assay of glutathione reductase using 5,5’-dithiobis(2-nitrobenzoic acid). Anal. Biochem. V. 183. P. 195. https://doi.org/10.1016/0003-2697(89)90188-7</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Damri O., Natour S., Agam G. 2021. Do autophagy enhancers/ROS scavengers alleviate consequences of mild mitochondrial dysfunction induced in neuronal-derived cells? Int. J. Mol. Sci. V. 22. P. 5753. https://doi.org/10.3390/ijms22115753</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Dangi A., Huang C., Tandon A., Stolz D., Wu T., Gandhi C. R. 2016. Endotoxin-stimulated rat hepatic stellate cells induce autophagy in hepatocytes as a survival mechanism. J. Cell Physiol. V. 231. P. 94. https://doi.org/10.1002/jcp.25055</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Deline M. L., Straub J., Patel M., Subba P., Grashei M., van Heijster F. H.A., Pirkwieser P., Somoza V., Livingstone J. D., Beazely M., Kendall B., Gingras M. J.P., Leonenko Z., Höschen C., Harrington G., Kuellmer K., Bian W., Schilling F., Fisher M. P.A., Helgeson M. E., Fromme T. 2023. Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity. Front. Physiol. V. 14. Art. ID: 1200119. https://doi.org/10.3389/fphys.2023.1200119</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Dossymbekova R., Bgatova N., Tungushbayeva Z., Sharipov K., Taneyeva G., Kydyrbaeva A., Solovieva A. 2020. Effect of lithium carbonate on autophagy and proliferative activity of isolated hepatocytes. Biochem. Biophys. Res. Commun. V. 528. P. 343. https://doi.org/10.1016/j.bbrc.2020.03.057</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Durak I., Yurtarslanl Z., Canbolat O., Akyol O. 1993. A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin. Chim. Acta. V. 214. P. 103. https://doi.org/10.1016/0009-8981(93)90307-p</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Engin A. B., Engin A., Engin E. D., Memis L. 2023. Does lithium attenuate the liver damage due to oxidative stress and liver glycogen depletion in experimental common bile duct obstruction? Toxicol. Appl. Pharmacol. V. 466. Art. ID: 116489. https://doi.org/10.1016/j.taap.2023.116489</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Halliwell G., Gutteridge J. M.C. 1999. Targets of attacks: fatty acids and lipoproteins. Free radicals in biology and medicine. N.-Y.: Oxford University Press.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Humbert M., Morán M., de la Cruz-Ojeda P., Muntané J., Wiedmer T., Apostolova N., McKenna S.L., Velasco G., Balduini W., Eckhart L., Janji B., Sampaio-Marques B., Ludovico P., Žerovnik E., Langer R., Perren A., Engedal N., Tschan M. P. 2020. Assessing autophagy in archived tissue or how to capture autophagic flux from a tissue snapshot. Biology (Basel). V. 9. Art. ID: 59. https://doi.org/10.3390/biology9030059</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Jiang Z. Y., Woollard A. C., Wolff S. P. 1990. Hydrogen peroxide production during experimental protein glycation. FEBS Lett. V. 268. P. 69. https://doi.org/10.1016/0014-5793(90)80974-n</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Jung S. R., Lee J. H., Ryu H., Gao Y., Lee J. 2024. Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis. Korean J. Physiol. Pharmacol. V. 28. P. 31. https://doi.org/10.4196/kjpp.2024.28.1.31</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Kiełczykowska M., Polz-Dacewicz M., Kopciał E., Mitrus O., Kurzepa J., Marzec Z., Musik I. 2020. Selenium prevents lithium accumulation and does not disturb basic microelement homeostasis in liver and kidney of rats exposed to lithium. Ann. Agric. Environ. Med. V. 27. P. 129. https://doi.org/10.26444/aaem/105926</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>L’Abbate S., Nicolini G., Marchetti S., Forte G., Lepore E., Unfer V., Kusmic C. 2023. Lithium treatment induces cardiac dysfunction in mice. Int. J. Mol. Sci. V. 24. Art. ID: 15872. https://doi.org/10.3390/ijms242115872</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Liu A., Fang H., Dahmen U., Dirsch O. 2013. Chronic lithium treatment protects against liver ischemia/reperfusion injury in rats. Liver Transpl. V. 19. P. 762. https://doi.org/10.1002/lt.23666</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Ma X., McKeen T., Zhang J., Ding W. X. 2020. Role and mechanisms of mitophagy in liver diseases. Cells. V. 9. Art. ID: 837. https://doi.org/10.3390/cells9040837</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Masaki R., Yamamoto A., Tashiro Y. 1987. Cytochrome P-450 and NADPH-cytochrome P-450 reductase are degraded in the autolysosomes in rat liver. J. Cell Biol. V. 104. Art. ID: 1207. https://doi.org/10.1083/jcb.104.5.1207</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Maurer I. C., Schippel P., Volz H. P. 2009. Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue. Bipolar Disord. V. 11. P. 515. https://doi.org/10.1111/j.1399-5618.2009.00729.x</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Mizushima N., Yoshimori T., Levine B. 2010. Methods in mammalian autophagy research. Cell. V. 140. P. 313. https://doi.org/10.1016/j.cell.2010.01.028</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Nciri R., Allagui M. S., Bourogaa E., Saoudi M., Murat J. C., Croute F., Elfeki A. 2012. Lipid peroxidation, antioxidant activities and stress protein (HSP72/73, GRP94) expression in kidney and liver of rats under lithium treatment. J. Physiol. Biochem. V. 68. P. 11. https://doi.org/10.1007/s13105-011-0113-3</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Nciri R., Allagui M. S., Vincent C., Murat J. C., Croute F., El Feki A. 2010. Chronic lithium administration triggers an over-expression of GRP94 stress protein isoforms in mouse liver. Food Chem. Toxicol. V. 48. P. 1638. https://doi.org/10.1016/j.fct.2010.03.038</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Paglia D. E., Valentine W. N. 1967. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. V. 70. P. 158.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Qian H., Chao X., Williams J., Fulte S., Li T., Yang L., Ding W. X. 2021. Autophagy in liver diseases: a review. Mol. Aspects Med. V. 82. Art. ID: 100973. https://doi.org/10.1016/j.mam. 100973</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Roscoe J.M, Sevier C. S. 2020. Pathways for Sensing and Responding to Hydrogen Peroxide at the Endoplasmic Reticulum. Cells. V. 9. Art. ID: 2314. https://doi.org/10.3390/cells9102314</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Russi S., Sgambato A., Bochicchio A. M., Zoppoli P., Aieta M., Capobianco A. M.L., Ruggieri V., Zifarone E., Falco G., Laurino S. 2021. CHIR99021, trough GSK-3β targeting, reduces epithelioid sarcoma cell proliferation by activating mitotic catastrophe and autophagy. Int. J. Mol. Sci. V. 22. Art. ID: 11147. https://doi.org/10.3390/ijms222011147</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Rysted J. E., Lin Z., Walters G. C., Rauckhorst A. J., Noterman M., Liu G., Taylor E. B., Strack S., Usachev Y. M. 2021. Distinct properties of Ca2+ efflux from brain, heart and liver mitochondria: the effects of Na+, Li+ and the mitochondrial Na+/Ca2+ exchange inhibitor CGP37157. Cell Calcium. V. 96. Art. ID: 102382. https://doi.org/10.1016/j.ceca.2021.102382</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Samad N., Bilal K., Yasmin F., Khaliq S., Zaman A., Ayaz M. M. 2020. Effect of lithium chloride on d-galactose induced organs injury: possible antioxidative role. Pakistan J. Pharm. Sci. V. 33. P. 1795.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Sarkar S., Krishna G., Imarisio S., Saiki S., O’Kane C.J., Rubinsztein D. C. 2008. A rational mechanism for combination treatment of Huntington’s disease using lithium and rapamycin. Hum. Mol. Genet. V. 17. P. 170. https://doi.org/10.1093/hmg/ddm294</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Singh B., Bhaskar S. 2019. Methods for detection of autophagy in mammalian cells. Methods Mol. Biol. V. 2045. P. 245. https://doi.org/10.1007/7651_2018_190</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Singulani M. P., De Paula V. J.R., Forlenza O. V. 2021. Mitochondrial dysfunction in Alzheimer’s disease: therapeutic implications of lithium. Neurosci. Lett. V. 760. Art. ID: 136078. https://doi.org/10.1016/j.neulet.2021.136078</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Stäubli W., Hess R., Weibel E. R. 1969. Correlated morphometric and biochemical studies on the liver cell. II. Effects of phenobarbital on rat hepatocytes. J. Cell Biol. V. 42. Art. ID: 92. https://doi.org/10.1083/jcb.42.1.92</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Talebi M., Mohammadi Vadoud S. A., Haratian A., Talebi M., Farkhondeh T., Pourbagher-Shahri A.M., Samarghandian S. 2022. The interplay between oxidative stress and autophagy: focus on the development of neurological diseases. Behav. Brain Funct. V. 18. Art. ID: 3. https://doi.org/10.1186/s12993-022-00187-3</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Wang W., Lu D., Shi Y., Wang Y. 2024. Exploring the neuroprotective effects of lithium in ischemic stroke: a literature review. Int. J. Med. Sci. V. 21. P. 284. https://doi.org/10.7150/ijms.88195</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Wilkinson S. 2019. ER-phagy: shaping up and destressing the endoplasmic reticulum. FEBS J. V. 286. P. 2645. https://doi.org/10.1111/febs.14932</mixed-citation></ref></ref-list></back></article>
