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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">RUDN Journal of Medicine</journal-id><journal-title-group><journal-title xml:lang="en">RUDN Journal of Medicine</journal-title><trans-title-group xml:lang="ru"><trans-title>Вестник Российского университета дружбы народов. Серия: Медицина</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2313-0245</issn><issn publication-format="electronic">2313-0261</issn><publisher><publisher-name xml:lang="en">Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">52071</article-id><article-id pub-id-type="doi">10.22363/2313-0245-2025-30-3-386-395</article-id><article-id pub-id-type="edn">KXZLKL</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Physiology</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Физиология</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">Different effects of methionine isomers on biochemical and cytological indices of blood in experimental animals</article-title><trans-title-group xml:lang="ru"><trans-title>Различный эффект влияния изомеров метионина на биохимические и цитологические показатели крови экспериментальных животных</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7777-6825</contrib-id><contrib-id contrib-id-type="spin">7291-0160</contrib-id><name-alternatives><name xml:lang="en"><surname>Chuchkova</surname><given-names>Natalya N.</given-names></name><name xml:lang="ru"><surname>Чучкова</surname><given-names>Н. Н.</given-names></name></name-alternatives><email>mig05@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3390-4343</contrib-id><contrib-id contrib-id-type="spin">4421-9206</contrib-id><name-alternatives><name xml:lang="en"><surname>Pazinenko</surname><given-names>Ksenia A.</given-names></name><name xml:lang="ru"><surname>Пазиненко</surname><given-names>К. А.</given-names></name></name-alternatives><email>mig05@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1801-5353</contrib-id><contrib-id contrib-id-type="spin">9437-0083</contrib-id><name-alternatives><name xml:lang="en"><surname>Smetanina</surname><given-names>Marina V.</given-names></name><name xml:lang="ru"><surname>Сметанина</surname><given-names>М. В.</given-names></name></name-alternatives><email>mig05@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2885-5882</contrib-id><contrib-id contrib-id-type="spin">4072-0220</contrib-id><name-alternatives><name xml:lang="en"><surname>Kormilina</surname><given-names>Natalya V.</given-names></name><name xml:lang="ru"><surname>Кормилина</surname><given-names>Н. В.</given-names></name></name-alternatives><email>mig05@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4965-9044</contrib-id><contrib-id contrib-id-type="spin">7003-7603</contrib-id><name-alternatives><name xml:lang="en"><surname>Pazinenko</surname><given-names>Oleg A.</given-names></name><name xml:lang="ru"><surname>Пазиненко</surname><given-names>О. А.</given-names></name></name-alternatives><email>mig05@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Izhevsk State Medical University</institution></aff><aff><institution xml:lang="ru">Ижевский государственный медицинский университет</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2026-08-30" publication-format="electronic"><day>30</day><month>08</month><year>2026</year></pub-date><volume>30</volume><issue>3</issue><issue-title xml:lang="en">CELL BIOLOGY</issue-title><issue-title xml:lang="ru">КЛЕТОЧНАЯ БИОЛОГИЯ</issue-title><fpage>386</fpage><lpage>395</lpage><history><date date-type="received" iso-8601-date="2026-08-31"><day>31</day><month>08</month><year>2026</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2026, Chuchkova N.N., Pazinenko K.A., Smetanina M.V., Kormilina N.V., Pazinenko O.A.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2026, Чучкова Н.Н., Пазиненко К.А., Сметанина М.В., Кормилина Н.В., Пазиненко О.А.</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="en">Chuchkova N.N., Pazinenko K.A., Smetanina M.V., Kormilina N.V., Pazinenko O.A.</copyright-holder><copyright-holder xml:lang="ru">Чучкова Н.Н., Пазиненко К.А., Сметанина М.В., Кормилина Н.В., Пазиненко О.А.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://journals.rudn.ru/medicine/article/view/52071">https://journals.rudn.ru/medicine/article/view/52071</self-uri><abstract xml:lang="en"><p>Relevance. Excess methionine entering the body (with food, drugs, dietary supplements) is accompanied by toxic accumulation of homocysteine and adverse effects leading to the formation of pathology of some systems. Small amount of studies are devoted to the comparative effect of methionine isomers. Objective: to establish the features of the biological effect of methionine isomers used as a dietary supplement on biochemical and cytological parameters of the blood of experimental animals. Materials and methods. Experimental rats received a feed additive with an increased content of methionine in the form of DL-form (racemate DL-methionine, Belgium) or L-form (100% L-methionine, Fingres Biotech Inc, China) for 0.15 g / 100 g of animal weight. In control animals, the feed did not contain additives. After 25 days, blood was taken from the animals under ether anesthesia by transcardial puncture. The following was determined: homocysteine concentration (Axis-Shield PLC (UK)); cytological analysis of white and red blood was performed (System XS-500i hematological analyzer (Japan)); for qualitative assessment, blood smears were stained with the hematological dye Leukodif-200 (Lachema, Czech Republic) and viewed under a Carl Zeiss microscope (Germany) at a magnification of × 1000. The body’s allergization index and the erythrocyte loading coefficient were calculated. Statistical analysis was performed using the Shapiro-Wilk normality analysis of data distribution, one-way ANOVA analysis of variance, multiple comparisons were performed using the Tukey test. Results and discussion. Introduction of racemic mixture of DL-methionine resulted in increase of homocysteine in blood to 28.9 ± 2.65 (p = 0.05), L-form to 79.38 ± 3.91 (p = 0.05) μmol/l (in control 8.5 ± 0.6 μmol/l). In blood of animals of group 1 increase of absolute number of granulocytic forms of leukocytes (by 1.4 times, p = 0.049) was revealed, neutrophilia was noted. When introducing L-form of methionine in animals there was sharp decrease of both absolute (by 3.7 times in comparison with control group, p = 0.01) and relative number of neutrophils, appearance of hypersegmented forms of neutrophils and immature forms of eosinophils was noted. In both groups, allergic predisposition of the organism was manifested, more pronounced in animals with the introduction of the L-form of methionine, the allergization index was increased by 49.2 ± 3.61% (p = 0.01). With the introduction of the L-form, the number of platelets decreased; ESR increased; the erythrocyte loading coefficient increased by 15.7% (p = 0.043). Conclusion. Thus, the severity of hyperhomocysteinemia, the direction of the responses of white and red blood, the coefficients reflecting the allergic disposition of the body and the functional erythrocyte load with excessive administration of methionine as a dietary supplement are determined by the form of the isomer included in its composition.</p></abstract><trans-abstract xml:lang="ru"><p>Актуальность. Избыток метионина, поступающего в организм (с пищей, лекарствами, биодобавками), сопровождается токсическим накоплением гомоцистеина и неблагоприятными эффектами, приводящими к формированию патологии ряда систем. Сравнительному влиянию изомеров метионина посвящено незначительное количество работ. Цель исследования: установить особенности биологического действия изомеров метионина, используемого в качестве пищевой биодобавки, на биохимические и цитологические показатели крови экспериментальных животных. Материалы и методы. Экспериментальные крысы получали добавку к корму с повышенным содержанием метионина в виде DL-формы (рацемат DL-метионина, Бельгия), либо L-формы (100 % L-метионин, Fingres Biotech Inc, Китай) в количестве 0,15г/100г массы животного. У контрольных животных прикорм не содержал добавок. Через 25 дней у животных под эфирным наркозом транскардиальной пункцией забирали кровь. Определяли: концентрацию гомоцистеина (Axis-Shield PLC (Великобритания)); проводили цитологический анализ белой крови и красной крови (гематологический анализатор System XS-500i (Япония)); для качественной оценки мазки крови окрашивали с помощью гематологического красителя Лейкодиф-200 (Lachema, Чехия) и просматривали в микроскопе Carl Zeiss (Германия) при увеличении × 1000. Рассчитывали индекс аллергизации организма и нагрузочный эритроцитарный коэффициент. Статистический анализ проводили с использованием методов анализа на нормальность распределения данных по Шапиро-Уилка, однофакторный дисперсионный анализ ANOVA, множественные сравнения проводились с помощью теста Тьюки. Результаты и обсуждение. Введение рацемической смеси DL-метионина привело к повышению гомоцистеина в крови до 28,9 ± 2,65 (р = 0,05), L-формы до 79,38 ± 3,91 (р = 0,05) мкмоль/л (в контроле 8,5 ± 0,6 мкмоль/л). В крови животных 1-й группы было выявлено повышение абсолютного числа гранулоцитарных форм лейкоцитов (в 1,4 раза, p = 0,049), отмечался нейтрофилез. При введении L-формы метионина у животных было резко снижено как абсолютное (в 3,7 раза в сравнении с контрольной группой, p = 0,01), так и относительное количество нейтрофилов, отмечено появление гиперсегментированных форм нейтрофилов и незрелых форм эозинофилов. В обеих группах проявилась аллергическая настроенность организма, более выраженная у животных с введением L-формы метионина, индекса аллергизации был повышен на 49,2 ± 3,61 % (р = 0,01). При введении L-формы снижалось количество тромбоцитов; увеличивалась СОЭ; на 15,7 % (p = 0,043) повышался нагрузочный эритроцитарный коэффициент. Выводы. Таким образом, выраженность гипергомоцистеинемии, направленность ответных реакций белой и красной крови, коэффициентов, отражающих аллергическую настроенность организма и функциональную эритроцитарную нагрузку при избыточном введении метионина в качестве биодобавки, определяются формой изомера, входящего в ее состав.</p></trans-abstract><kwd-group xml:lang="en"><kwd>DL-methionine</kwd><kwd>L-methionine</kwd><kwd>hyperhomocysteinemia</kwd><kwd>clinical blood test</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>DL-метионин</kwd><kwd>L-метионин</kwd><kwd>гипергомоцистеинемия</kwd><kwd>клинический анализ крови</kwd></kwd-group><funding-group/></article-meta><fn-group/></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Alkaissi H, McFarlane SI. Hyperhomocysteinemia and Accelerated Aging: The Pathogenic Role of Increased Homocysteine in Atherosclerosis, Osteoporosis, and Neurodegeneration. Cureus. 2023;15(7):e42259. doi: 10.7759/cureus.42259</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Guieu R, Ruf J, Mottola G.  Hyperhomocysteinemia and cardiovascular diseases. Ann Biol Clin (Paris). 2022;80(1):7–14. doi: 10.1684/abc.2021.1694</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Marroncini G, Martinelli S, Menchetti S, Bombardiere F, Martelli FS. Hyperhomocysteinemia and Disease-Is 10 μmol/L a Suitable New Threshold Limit? Int J Mol Sci. 2024;25(22):12295. doi: 10.3390/ijms252212295</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Nieraad H, Pannwitz N, Bruin N, Geisslinger G, Till U. Hyperhomocysteinemia: Metabolic Role and Animal Studies with a Focus on Cognitive Performance and Decline-A Review. Biomolecules. 2021;11(10):1546. doi: 10.3390/biom11101546</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Son P, Lewis L. Hyperhomocysteinemia. 2020 May 21. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.</mixed-citation></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">Pazinenko KA, Chuchkova NN, Smetanina MV, Pazinenko OA, Panteleev KE, Ivanov GV, Kormilina NV. Dynamics of biochemical and cytological parameters of rat blood in modeling chronic alimentary methionine-induced homocysteineemia. Biomedicine. 2021;17(2):46–57. (In Russian). doi: 10.33647/2074-5982-17-2-46-57.</mixed-citation><mixed-citation xml:lang="ru">Пазиненко К.А., Чучкова Н.Н., Сметанина М.В., Пазиненко О.А., Пантелеев К.Э.,  Иванов Г.В., Кормилина Н.В. Динамика биохимических и цитологических показателей крови крыс при моделировании хронической алиментарной метионин-обусловленной гомоцистеинемии // Биомедицина. 2021. Т. 17, № 2. С. 46–57. https://doi.org/10.33647/2074-5982-17-2-46-57.</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><mixed-citation>Kovalska M, Baranovicova E, Kalenska D, Tomascova A, Adamkov M, Kovalska L, Lehotsky J. Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats. Int J Mol Sci. 2021;22(9):4961. doi: 10.3390/ijms22094961</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Fan J, Zheng F, Li S, Cui C, Jiang S, Zhang J, Cai J, Cui Q, Yang J, Tang X, Xu G, Geng B. Hydrogen sulfide lowers hyperhomocysteinemia dependent on cystathionine γ lyase S-sulfhydration in ApoE-knockout atherosclerotic mice. Br J Pharmacol. 2019;176(17):3180–3192. doi: 10.1111/bph.14719</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Leong XF, Ng CY, Jaarin K. Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis. Biomed Res Int. 2015;2015:528757. doi: 10.1155/2015/528757</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Dalton GL, Floresco SB, Phillips AG. Differential effects of d- and l-enantiomers of govadine on distinct forms of cognitive flexibility and a comparison with dopaminergic drugs. Psychopharmacology (Berl). 2021;238(4):1069–1085. doi: 10.1007/s00213-020-05754‑y</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Kesić J, Popsavin M, Benedeković G, Kojić V, Bosak A, Matošević A, Farkaš P, Madelová R, Popsavin V, Kovačević I. Synthesis and biological evaluation of natural cleistanolate, its enantiomer and analogues. Eur J Med Chem. 2025;287:117326. doi: 10.1016/j.ejmech.2025.117326</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Espinosa CD, Mathai JK, Blavi L, Liu Y, Htoo JK, Caroline Gonzalez-Vega J, Stein HH. Effects of supplemental d-methionine in comparison to l-methionine on nitrogen retention, gut morphology, antioxidant status, and mRNA abundance of amino acid transporters in weanling pigs. J Anim Sci. 2021;99(9): skab248. doi: 10.1093/jas/skab248</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Murtas G, Pollegioni L. D-Amino Acids and Cancer: Friends or Foes? Int J Mol Sci. 2023;24(4):3274. doi: 10.3390/ijms24043274</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Zeitz JO, Kaltenböck S, Most E, Eder K. Effects of L-methionine on performance, gut morphology and antioxidant status in gut and liver of piglets in relation to DL-methionine. J Anim Physiol Anim Nutr (Berl). 2019;103(1):242–250. doi: 10.1111/jpn.13000</mixed-citation></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">Mokasheva Ek N, Mokasheva Evg N. Leukocyte indices in patients with therapeutic and surgical profiles. Scientific Review. Medical Sciences. 2024;3:24–29. (In Russian). https://doi.org/10.17513/srms.1400.</mixed-citation><mixed-citation xml:lang="ru">Мокашева Ек.Н., Мокашева Евг.Н. Лейкоцитарные индексы у пациентов терапевтического и хирургического профиля // Научное обозрение. Медицинские науки. 2024. № 3. С. 24–29; doi: https://doi.org/10.17513/srms.1400.</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">Mel NP. The influence of antibiotics on the mother-fetus system and the health of newborns: Dis. for the degree of candidate of medical sciences: 03.00.07. Vladivostok, 1990. (In Russian).</mixed-citation><mixed-citation xml:lang="ru">Мель Н.П. Влияние антибиотиков на систему мать-плод и здоровье новорожденных: дис. на соискание степени канд. мед. наук: спец. 03.00.07. Владивосток, 1990.</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><mixed-citation>Shi Y, Hussain Z, Zhao Y. Promising Application of D-Amino Acids toward Clinical Therapy. Int J Mol Sci. 2022;23(18):10794. doi: 10.3390/ijms231810794</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Kimura R, Ueda R, Tsujimura H, Ban T, Tanaka A. Urinary D-amino acid profiles in cats with chronic kidney disease. J Vet Med Sci. 2024;86(8):855–859. doi: 10.1292/jvms.24-0023</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Pandey R, Tiziani S. Advances in Chiral Metabolomic Profiling and Biomarker Discovery. Methods Mol Biol. 2025;2855:85–101. doi: 10.1007/978-1-0716-4116-3_5</mixed-citation></ref><ref id="B20"><label>20.</label><citation-alternatives><mixed-citation xml:lang="en">Gaidukova TV, Galak IR, Bogdanov IA, Reshetnikov IA, Baldanov AA. Homocysteine and neutrophil functions in vitro. Youth Research Potential 2023. Petrozavodsk : International Center for Scientific Partnership «New Science», Р. 75–84. (In Russian). doi 10.46916/24022023-1-978-5-00174-884-7</mixed-citation><mixed-citation xml:lang="ru">Гайдукова Т.В., Галак И.Р., Богданов И.А., Решетников И.А., Балданов А.А. Гомоцистеин и функции нейтрофилов in vitro. Молодежный исследовательский потенциал. Петрозаводск : Международный центр научного партнерства «Новая Наука», 2003.С. 75–84. doi: 10.46916/24022023-1-978-5-00174-884-7.</mixed-citation></citation-alternatives></ref><ref id="B21"><label>21.</label><mixed-citation>Skinner BM, Johnson EE. Nuclear morphologies: their diversity and functional relevance. Chromosoma. 2017;126(2):195–212. doi: 10.1007/s00412-016-0614-5</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Harada T, Swift J, Irianto J, Shin JW, Spinler KR, Athirasala A, Diegmiller R, Dingal PC, Ivanovska IL, Discher DE. Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J Cell Biol. 2014;204(5):669–82. doi: 10.1083/jcb.201308029</mixed-citation></ref><ref id="B23"><label>23.</label><citation-alternatives><mixed-citation xml:lang="en">Hoang TH, Maiskov VV, Merai IA, Kobalava ZD. Prognostic value of red cell distribution width in acute myocardial infarction. RUDN Journal of Medicine. 2025;29(2):143–152. (In Russian). doi: 10.22363/2313-0245-2025-29-2-143-152. EDN: TAXBMI.</mixed-citation><mixed-citation xml:lang="ru">Хоанг Ч.Х., Майсков В.В., Мерай И.А., Кобалава Ж.Д. Прогностическое значение ширины распределения эритроцитов при остром инфаркте миокарда // Вестник Российского университета дружбы народов. Серия: Медицина. 2025. Т. 29, № 2. C. 143–152. doi: 10.22363/2313-0245-2025-29-2-143-152 EDN: TAXBMI</mixed-citation></citation-alternatives></ref><ref id="B24"><label>24.</label><mixed-citation>Troen AM, Lutgens E, Smith DE, Rosenberg IH, Selhub J. The atherogenic effect of excess methionine intake. Proc Natl Acad Sci U S A. 2003;100(25):15089–94. doi: 10.1073/pnas.2436385100</mixed-citation></ref></ref-list></back></article>
