<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<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">Russian Journal of Physiology</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Physiology</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский физиологический журнал им. И.М. Сеченова</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0869-8139</issn><issn publication-format="electronic">2658-655X</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">687413</article-id><article-id pub-id-type="doi">10.31857/S0869813925060074</article-id><article-id pub-id-type="edn">TEWXWN</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>EXPERIMENTAL ARTICLES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ЭКСПЕРИМЕНТАЛЬНЫЕ 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">Polyphenols from <italic>Vitis vinifera</italic> L. Grape Stems Regulate Alcohol Metabolism and Reduce Its Toxic Effects in Rats</article-title><trans-title-group xml:lang="ru"><trans-title>Полифенолы гребней винограда <italic>vitis vinifera l.</italic> регулируют метаболизм этилового спирта и снижают его токсическое действие у крыс</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Fomenko</surname><given-names>S. E.</given-names></name><name xml:lang="ru"><surname>Фоменко</surname><given-names>С. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>fomenko29@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kushnerova</surname><given-names>N. F.</given-names></name><name xml:lang="ru"><surname>Кушнерова</surname><given-names>Н. Ф.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>fomenko29@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Sprygin</surname><given-names>V. G.</given-names></name><name xml:lang="ru"><surname>Спрыгин</surname><given-names>В. Г.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>fomenko29@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Ilyichev Pacific Oceanological Institute FEB RAS</institution></aff><aff><institution xml:lang="ru">Тихоокеанский океанологический институт им. В.И. Ильичева ДВО РАН</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2025-06-15" publication-format="electronic"><day>15</day><month>06</month><year>2025</year></pub-date><volume>111</volume><issue>6</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>929</fpage><lpage>943</lpage><history><date date-type="received" iso-8601-date="2025-07-13"><day>13</day><month>07</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-07-13"><day>13</day><month>07</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://journals.eco-vector.com/0869-8139/article/view/687413">https://journals.eco-vector.com/0869-8139/article/view/687413</self-uri><abstract xml:lang="en"><p>The study examined the effect of <italic>Vitis vinifera</italic> L. grape stem (bunch after berry separation) extract enriched with a polyphenol complex on ethanol elimination and the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (AlDH) in rat liver under chronic alcohol intoxication. The total content of polyphenols in the resulting extract was 53.12 ± 1.25 mg GAE/g dw extract (mg-equivalent of gallic acid/g) and flavonoids – 8.02 ± 2.6 mg GAE/g dw extract (mg-equivalent of quercetin/g). Under the influence of 5% grape stem extract (GSE) added to a 15% ethanol solution, a decrease in ethyl alcohol consumption by animals was observed, both under conditions of free access and forced contact with ethanol. Comparative analysis of ethanol pharmacokinetic parameters in rats showed that the addition of GSE leads to a decrease in ethanol elimination from the body, as evidenced by an increase in the half-life (T<sub>1/2</sub>) and a decrease in the ethanol elimination constant (K<sub>el</sub>) in the blood. It was found that the complex of polyphenols contained in plant extracts plays a major role in the processing of ethyl alcohol in other animals, being exposed to enzymes that occur in its oxidation. The action of GSE leads to an increase in the reductase activity of ADH in the liver, which helps prevent the accumulation of highly toxic acetaldehyde in the body. This fact is confirmed by a decrease in the activity of the AlDG enzyme in the liver of rats with both low and high Michaelis constants. The polyphenol complex isolated from grape stem can serve as an effective means of protecting the body from the toxic effects of high doses of ethyl alcohol.</p></abstract><trans-abstract xml:lang="ru"><p>В процессе исследования оценивалось влияние экстракта из гребней (кисти после отделения ягод) винограда <italic>Vitis vinifera </italic>L., обогащенного полифенольным комплексом, на элиминацию этанола и активность алкогольдегидрогеназы (АДГ) и альдегиддегидрогеназы (АлДГ) в печени крыс в условиях хронической алкогольной интоксикации. Общее содержание полифенолов в полученном экстракте составило 53.12 ± 1.25 мг-экв ГК/г сухого экстракта (мг-эквивалент галловой кислоты/г) и флавоноидов – 8.02 ± 2.6 мг-экв Кв/г сухого экстракта (мг-эквивалент кверцетина/г). Под действием 5%-ного экстракта из гребней винограда (ЭГВ), добавленного в 15%-ный раствор этанола, наблюдалось снижение потребления этилового спирта животными как в условиях свободного доступа, так и принудительного контакта с этанолом. Сравнительный анализ фармакокинетических параметров этанола в крови крыс показал, что добавка ЭГВ приводит к снижению элиминации этанола из организма, о чем свидетельствует увеличение времени полувыведения (T<sub>1/2</sub>) и уменьшение константы элиминации этанола (K<sub>el</sub>). Установлено, что комплекс полифенолов, содержащихся в экстракте растительного происхождения, играет важную роль в метаболизме этилового спирта в организме животных, оказывая воздействие на ферменты, участвующие в его окислении. Действие ЭГВ приводит к увеличению редуктазной активности АДГ в печени, что помогает предотвратить накопление высокотоксичного ацетальдегида в организме. Данный факт подтверждается снижением активности фермента АлДГ в печени крыс как с низкой, так и с высокой константой Михаэлиса. Комплекс полифенолов, выделенный из виноградных гребней, может стать эффективным средством для защиты организма от токсического воздействия высоких доз этилового спирта.</p></trans-abstract><kwd-group xml:lang="en"><kwd>polyphenols</kwd><kwd>Vitis vinifera</kwd><kwd>ethanol</kwd><kwd>crests</kwd><kwd>rats</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>полифенолы</kwd><kwd>Vitis vinifera</kwd><kwd>этанол</kwd><kwd>печень</kwd><kwd>крысы</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Тихоокеанского океанологического института им. В.И. Ильичева Дальневосточного отделения РАН</institution></institution-wrap><institution-wrap><institution xml:lang="en">Ilyichev Pacific Oceanological Institute FEB RAS</institution></institution-wrap></funding-source><award-id>124022100077-0</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Teschke R (2018) Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects. Biomedicines 6(4): 106. https://doi.org/10.3390/biomedicines6040106</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Zhao J, Stockwell T, Naimi T, Churchill S, Clay J, Sherk A (2023) Association Between Daily Alcohol Intake and Risk of All-Cause Mortality: A Systematic Review and Meta-analyses. JAMA Netw Open 6(3): e236185. https://doi.org/10.1001/jamanetworkopen.2023.6185</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Lieber CS (2009) Alcohol and the Liver: Metabolism of Ethanol, Metabolic Effects and Pathogenesis of Injury. Acta Med Scand 218: 11-55. http://dx.doi.org/10.1111/j.0954-6820.1985.tb08903.x</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Lieber CS (2005) Metabolism of alcohol. Clin Liver Dis 9: 1–35. https://doi.org/10.1016/j.cld.2004.10.005</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Lieber CS (2004) The discovery of the ethanol oxidizing system and its physiologic and pathologic role. Drug Metab Rev 36(3-4): 511–529. https://doi.org/10.1081/dmr-200033441</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Clemens DL, Forman A, Jerrels TR (2002) Relationship between acetaldehyde levels and cell survival in ethanol-metabolizing hepatoma cells. Hepatology 35(5): 1196–1204. https://doi.org/10.1053/jhep.2002.32668</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>French SW (2000) Mechanism of alcoholic liver injury. Can J Gastroenterol 14(4): 327–332. https://doi.org/10.1155/2000/801735</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Lelevich SV, Borodinskii AN (2009) Particuliarities of glycolysis in liver and skeletal muscle after acute alcohol intoxication in rats. Biomed Khim 55(1): 106–113.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Шерлок Ш, Дули Дж (2002) Заболевания печени и желчных путей. ЗГ Апросина НА Мухина (ред) М. Гэотар. Медицина. [Sherlok SH, Duli Dzh (2002) Diseases of the liver and bilary tract. ZG Aprosinoj, NA Muhina (eds) M. Geotar. Medicina. (In Russ)].</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Stewart SF, Day CP (2004) Alcoholic liver disease. The liver in biology and disease. Princip Med Biol 15: 317–359.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Sakai K, Yamane T, Saitoh Y, Ikawa C, Nishihata T (1987) Effect of water extracts of crude drugs in decreasing blood ethanol concentrations in rats. Chem Pharm Bull 35(11): 4597–4604. https://doi.org/10.1248/cpb.35.4597</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Yamazaki T, Hosono T, Matsushita Y, Kawashima K, Someya M, Nakajima Y, Narui K, Hibi Y, Ishizaki M, Kinjo J, Nohara T (2002) Pharmacological studies on Puerariae Flos. IV: Effects of Pueraria thomsonii dried flower extracts on blood ethanol and acetaldehyde levels in humans. Int J Clin Pharmacol Res 22(1): 23–28.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Wen-Zhe Li, Jie Lu, Xiao-Yu Sun, Shi-Long Wang, Ya-Ming Ni, Wen-Si Zhu (2006) Studies on the effect of extracts of several Chinese herbal medicines and other medicines on alcohol dehydrogenase activity. Zhong Yao Cai 29(8): 816–818.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Panche AN, Diwan AD, Chandra SR (2016) Flavonoids: an overview. J Nutr Sci 29(5): e47. https://doi.org/10.1017/jns.2016.41</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Фоменко СЕ, Кушнерова НФ, Спрыгин ВГ, Гордейчук ТН (2003) Сравнительная оценка эффективности применения растительных комплексов для восстановления метаболических процессов в печени после поражения этиловым спиртом. Наркология 3: 37–42. [Fomenko SE, Kushnerova NF, Sprygin VG, Gordejchuk TN (2003) Comparative evaluation of the effectiveness of the use of herbal complexes for the restoration of metabolic processes in the liver after damage by ethyl alcohol. Narcology 3: 37–42. (In Russ)].</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Спрыгин ВГ (2012) Применение олигомерных проантоцианидинов для профилактики метаболических нарушений углеводного обмена в печени крыс при поражении этиловым спиртом. Сибирск мед журн 111(4): 131–134. [Sprygin VG (2012) The use of oligomeric proanthocyanidins for the prevention of metabolic disorders of carbohydrate metabolism in the liver of rats affected by ethyl alcohol. Siber Med J 111(4): 131–134. (In Russ)].</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Nassiri-Asl M, Hosseinzadeh H (2016) Review of the Pharmacological Effects of Vitis vinifera (Grape) and its Bioactive Constituents: An Update. Phytother Res 30: 1392–1403. https://doi.org/10.1002/ptr.5644</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Khadher TB, Aydi S, Mars M, Bouajila J (2022) Study on the Chemical Composition and the Biological Activities of Vitis vinifera Stem Extracts. Molecules 27: 3109. http://dx.doi.org/10.3390/molecules27103109</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Lekakis J, Rallidis LS, Andreadou I, Vamvakou G, Kazantzoglou G, Magiatis P, Skaltsounis A-L, Kremastinos DT (2005) Polyphenols Compounds from Red Grapes Acutely Improve Endothelial Function in Patients with Coronary Heart Disease. Eur J Prev Cardiol 12: 596–600. https://doi.org/10.1097/00149831-200512000-00013</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Mukherjee S, Das SK, Vasudevan DM (2012) Dietary grapes (Vitis vinifera) feeding attenuates ethanol-induced oxidative stress in blood and modulates immune functions in mice. Ind J Biochem Biophys 49(5): 379–385.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Suresh A, Chinnasamy V, Anbu S (2019) Effect of grape leaf extract on the alcoholic induced lipid profile changes in rats. Pharma Innovat J 8(6): 371–375.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Saadaoui N, Weslati A, Barkaoui T (2019) Gastroprotective effect of leaf extract of two varieties grapevine (Vitis vinifera L.) native wild and cultivar grown in North of Tunisia against the oxidative stress induced by ethanol in rats. Biomarkers 25(1): 48–61. https://doi.org/10.1080/1354750x.2019.1691266</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Sun GY, Xia J, Xu J, Allenbrand B, Simonyi A, Rudeen PK, Sun AY (1999) Dietary supplementation of grape polyphenols to rats ameliorates chronic ethanol-induced changes in hepatic morphology without altering changes in hepatic lipids. J Nutr 129(10): 1814–1819. https://doi.org/10.1093/jn/129.10.1814</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Laufenberg G, Kunz B, Nystroem M (2003) Transformation of Vegetable Waste into Value Added Products; (A) the Upgrading Concept; (B) Practical Implementations. Bioresour Technol 87: 167–198. https://doi.org/10.1016/s0960-8524(02)00167-0</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Спрыгин ВГ, Кушнерова НФ (2006) Природные олигомерные проантоцианидины – перспективные регуляторы метаболических нарушений. Вестн Дальневосточн отдел Рос акад наук 2(126): 81–90. [Sprygin VG, Kushnerova NF (2006) Natural oligomeric proanthocyanidins are promising regulators of metabolic disorders. Vestn Far Eastern Department Russ Acad Sci 2(126): 81–90. (In Russ)].</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Spranger I, Sun B, Mateus AM, Freitas V, Ricardo-da-Silva JM (2008) Chemical characterization and antioxidant activities of oligomeric and polymeric procyanidin fractions from grape seeds. Food Chem 108(2): 519–532. https://doi.org/10.1016/j.foodchem.2007.11.004</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Gonzalez-Centeno MR, Jourdes M, Femenia A, Simal S, Rossello C, Teissedre PL (2012) Proanthocyanidin composition and antioxidant potential of the stem winemaking byproducts from 10 different grape varieties (Vitis vinifera L.). J Agric Food Chem 60: 11850–11858. https://doi.org/10.1021/jf303047k</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Singleton VL, Orthofer R, Lamuela-Raventós RM (1998) Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin–Ciocalteu reagent. Methods Enzymol 299: 152–178. https://doi.org/10.1016/S0076-6879(99)99017-1</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Chandra S, Khan S, Avula B, Lata H, Yang MH, ElSohly MA, Khan IA (2014) Assessment of Total Phenolic and Flavonoid Content, Antioxidant Properties, and Yield of Aeroponically and Conventionally Grown Leafy Vegetables and Fruit Crops: A Comparative Study. Evid. Based Complement. Altern Med 4: 253875. http://dx.doi.org/10.1155/2014/253875</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Кампов-Полевой АБ (1982) Изучение особенностей формирования алкогольной мотивации у крыс В: Фармакология экспериментального алкоголизма. ЮВ Буров (ред) М. 130–135. [Kampov-Polevoj AB (1982) The study of the peculiarities of alcohol motivation formation in rats. In: The pharmacology of experimental alcoholism. YuV Burov (ed) M. 130–135. (In Russ)].</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Власова НВ (1982) Особенности кинетики этанола в крови крыс при экспериментальном алкоголизме. В: Фармакология экспериментального алкоголизма. ЮВ Буров (ред) М. 119–123. [Vlasova NV (1982) Features of ethanol kinetics in rat blood in experimental alcoholism. In: Pharmacology of experimental alcoholism. YuV Burov (ed) M. 119–123. (In Russ)].</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Ostrovsky YM, Pronko PS, Shishkin SN, Kolesnikov VB, Volynets SI (1989) An attempt to evaluate diagnostic and prognostic significance of blood endogenous ethanol in alcoholics and their relatives. Alcohol 6(2): 97–102. https://doi.org/10.1016/0741-8329(89)90032-3</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Соловьев ВН, Фирсов АД, Филов ВА (1980) Фармакокинетика. М. Медицина. [Solov'ev VN, Firsov AD, Filov VA (1980) Farmakokinetiks. M. Medicina. (In Russ)].</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Shimasue A, Murakami M, Tsubokura TA (1972) Specific method for the assay of alcohol dehydrogenase in human liver and serum. Hiroshima J Med Sci 21(4): 131–140.</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Tottmar CSO, Pettersson H, Kiessling KH (1973) The subcellular distribution and properties of aldehyde dehydrogenases in rat liver. Biochem J 135(4): 577–586. https://doi.org/10.1042/bj1350577a</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Razvdovskiĭ Iu E, Doroshenko EM (2007) Effect of taurine on the pool of central neuroactive compounds during ethanol withdrawal syndrome. Eksp Klin Farmakol 70(5): 38–43. [In Russ].</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Bardina LR, Pron'ko PS, Satanovskaia VI, Alieva EV (2010) Effects of catalase activators and inhibitors on ethanol pharmacokinetic characteristics and ethanol and aldehyde-metabolizing enzyme activities in the rat liver and brain. Biomed Khim 56(4): 499–505. [Article in Russ].</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Буров ЮВ, Абсаева ГИ, Кампов-Полевой АБ, Клюев СМ (1981) Элиминация этанола у белых крыс с различным уровнем алкогольной мотивации. Фармакол токсикол 44(1): 50–51. [Burov YV, Absaeva GI, Kampov-Polevoj AB, Klyuev SM (1981) Elimination of ethanol in white rats with different levels of alcohol motivation. Pharmacol Toxicol 44(1): 50–51. (In Russ)].</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Weiss F, Porrino LJ (2002) Behavioral neurobiology of alcohol addiction: Recent advances and challenges. J Neurosci 22(9): 3332–3337. https://doi.org/10.1523/jneurosci.22-09-03332.2002</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Morales-Gonzalez JA, Gutierrez-Salinas J, Hernandez-Munoz R (1998) Pharmacokinetics of the ethanol bioavailiability in the regenerating rat liver induced by partial hepatectomy. Alcohol Clin Exp Res 22: 1557–1563. https://doi.org/10.1111/j.1530-0277.1998.tb03949.x.</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Островский ЮМ, Сатановская ВИ (1988) Метаболические предпосылки и последствия потребления алкоголя. Минск. Наука и техника. [Ostrovskij YuM, Satanovskaya VI (1988) Metabolic background and consequences of alcohol consumption. Minsk. Science and Technology. (In Russ)].</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Pietruszko R (1980) Alcohol and aldehyde dehydrogenase isozymes from mammalian liver-their structural and functional differences. Isozymes Curr Top Biol Med Res 4: 107–130.</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>López-Valencia V, Rangel P, Rodríguez S, Hernández-Muñoz R (2007) Involvement of alcohol and aldehyde dehydrogenase activities on hepatic retinoid metabolism and its possible participation in the progression of rat liver regeneration. Biochem Pharmacol 73(4): 86–96. https://doi.org/10.1016/j.bcp.2006.10.021</mixed-citation></ref></ref-list></back></article>
