{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:56:16Z","timestamp":1791374176255,"version":"4.3.1"},"reference-count":48,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education, Russian Federation","award":["125020701774-6"],"award-info":[{"award-number":["125020701774-6"]}]},{"name":"Ministry of Science and Higher Education, Russian Federation","award":["125020701775-3"],"award-info":[{"award-number":["125020701775-3"]}]},{"name":"Ministry of Science and Higher Education, Russian Federation","award":["1024040100164-7"],"award-info":[{"award-number":["1024040100164-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>We investigated the antiradical properties of antioxidants: carnitinate 2-ethyl-6-methyl-3-hydroxypyridine (CAR-3-HP) and carboxychromate-2-ethyl-6-methyl-3-hydroxypyridine (CCR-3-HP), and also assessed the mitochondrial response to stress (hypoxia) by analyzing the intensity of lipid peroxidation, membrane fatty acid composition, and activation of autophagy markers LC3 and Beclin-1 using spectrofluorimetry, chromatography, and immunoblotting, respectively. The studied antioxidants exhibited high antiradical activity, which was reflected in their ability to inhibit lipid peroxidation. Five-day administration of antioxidants to mice at a dose of 2 \u00d7 10\u22129 mol\/kg prevented the activation of lipid peroxidation in liver mitochondrial membranes under conditions of acute hypobaric hypoxia. The drugs also prevented a decrease in C18 and C20 fatty acid levels, and also activated autophagy. In both cases, CAR-3-HP was more effective than CCR-3-HP. This drug increased the lifespan of mice almost twice as effectively under conditions of various types of hypoxias.<\/jats:p>","DOI":"10.3390\/ijms27198903","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:34:31Z","timestamp":1791372871000},"page":"8903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biological Activity of 3-Hydroxypyridine Derivatives with Natural Components"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3790-1112","authenticated-orcid":false,"given":"Irina V.","family":"Zhigacheva","sequence":"first","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, St. Kosygin, 4, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Elena M.","family":"Mil","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, St. Kosygin, 4, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Irina F.","family":"Rusina","sequence":"additional","affiliation":[{"name":"N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, St. Kosygin, 4, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-456X","authenticated-orcid":false,"given":"Natalya I.","family":"Krikunova","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, St. Kosygin, 4, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Ludmila I.","family":"Matienko","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, St. Kosygin, 4, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Timur L.","family":"Veprintsev","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, St. Kosygin, 4, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4348-0409","authenticated-orcid":false,"given":"Anastasia A.","family":"Albantova","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, St. Kosygin, 4, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Alexander N.","family":"Goloshchapov","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, St. Kosygin, 4, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Endale, H.T., Tesfaye, W., and Mengstie, T.A. (2023). ROS induced lipid peroxidation and their role in ferroptosis. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1226044"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9912436","DOI":"10.1155\/2021\/9912436","article-title":"Reactive Oxygen Species (ROS) Regulates Different Types of Cell Death by Acting as a Rheostat","volume":"2021","author":"Gibson","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Liu, W., Hu, M.D., Cao, F., and Jin, S. (2025). Polyphenols and exercise in autophagy regulation: Potential benefits for cancer management and healthspan. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1618813"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104989","DOI":"10.1016\/j.yexmp.2025.104989","article-title":"The interplay involving oxidative stress and autophagy: Mechanisms, implications, and therapeutic opportunities","volume":"143","author":"Gouda","year":"2025","journal-title":"Exp. Mol. Pathol."},{"key":"ref_6","first-page":"50","article-title":"Test system for evaluation of the influence of the biological activity of substances on the signal system of NF-\u03baB: Focus on the derivatives of 3- hydroxypyridine derivatives of 3- hydroxypyridine","volume":"3","author":"Skachilova","year":"2017","journal-title":"Res. Result Pharmacol. Clin. Pharmacol."},{"key":"ref_7","unstructured":"Verma, C., and Verma, D.K. (2023). Vitamins and metabolites. Handbook of Biomolecules Fundamentals, Properties and Applications, Elsevier."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.19163\/2307-9266-2023-11-1-48-61","article-title":"Protective Role 3-Oxypyridine Derivations in Steroid-Induced Osteoporosis in Rats Associated with Reduction of oxidative Stress and Restoration of Nitric Oxide Formation","volume":"11","author":"Danilenko","year":"2023","journal-title":"Pharm. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gnoni, A., Longo, S., Gnoni, G.V., and Giudetti, A.M. (2020). Carnitine in Human Muscle Bioenergetics: Can Carnitine Supplementation Improve Physical Exercise?. Molecules, 25.","DOI":"10.3390\/molecules25010182"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1186\/s12967-025-06341-5","article-title":"Comprehensive review of the expanding roles of the carnitine pool in metabolic physiology: Beyond fatty acid oxidation","volume":"23","author":"Xiang","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1039\/c3cp43319f","article-title":"A physicochemical examination of the free radical scavenging activity of Trolox: Mechanism, kinetics and influence of the environment","volume":"15","author":"Alberto","year":"2013","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1134\/S1990793122010274","article-title":"Antioxidant activity of diatomic phenols","volume":"16","author":"Rusina","year":"2022","journal-title":"Russ. J. Phys. Chem. B."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1134\/S1990793113040192","article-title":"Chemiluminescent methods for studying inhibited oxidation","volume":"7","author":"Rusina","year":"2013","journal-title":"Russ. J. Phys. Chem. B."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1021\/tx020012t","article-title":"Determination of the alpha-tocopherol inhibition rate constant for peroxidation in low-density lipoprotein","volume":"15","author":"Culbertson","year":"2002","journal-title":"Chem. Res. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0003-2697(73)90327-8","article-title":"Measurement of fluorescent lipid peroxidation products in biological systems and tissues","volume":"52","author":"Fletcher","year":"1973","journal-title":"Anal. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, H., Song, T.-Y., Reyes-Garc\u00eda, J., and Wang, Y.-X. (2024). Hypoxia-Induced Mitochondrial ROS and Function in Pulmonary Arterial Endothelial Cells. Cells, 13.","DOI":"10.3390\/cells13211807"},{"key":"ref_17","first-page":"157","article-title":"Dynamics of lipid peroxidation of membranes in cells and mitochondrial fraction of neocortex in non- and preconditioned rats after severe hypobaric hypoxia","volume":"47","author":"Kislin","year":"2011","journal-title":"Zh. Evol. Biokhim. Fiziol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1134\/S0006350916020032","article-title":"The generation of superoxide radicals by complex III in heart mitochondria and the antioxidant effect of dinitrosyl iron complexes at different partial pressures of oxygen","volume":"61","author":"Dudylina","year":"2016","journal-title":"Biophysics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/S0021-9673(00)88356-9","article-title":"Adaptation of macroscal method to the microscale for fatty acid methyl transesterification of biological lipid extracts","volume":"151","author":"Carreau","year":"1979","journal-title":"J. Chromatogr. A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1093\/ps\/79.8.1168","article-title":"Fatty acid determination in chicken egg yolk: A comparison of different methods","volume":"79","author":"Wang","year":"2000","journal-title":"Poult. Sci."},{"key":"ref_21","first-page":"130","article-title":"Prostaglandins: An overview","volume":"11","author":"Kushwaha","year":"2023","journal-title":"Eur. J. Pharm. Med. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101679","DOI":"10.1016\/j.redox.2020.101679","article-title":"Complex interplay between autophagy and oxidative stress in the development of pulmonary disease","volume":"36","author":"Ornatowski","year":"2020","journal-title":"Redox Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rossin, D., Perrelli, M.-G., Lo Iacono, M., Rastaldo, R., and Giachino, C. (2025). Dynamic Interplay Between Autophagy and Oxidative Stress in Stem Cells: Implications for Regenerative Medicine. Antioxidants, 14.","DOI":"10.3390\/antiox14060691"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/cdd.2014.150","article-title":"Oxidative stress and autophagy: The clash between damage and metabolic needs","volume":"22","author":"Filomeni","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.molcel.2010.09.023","article-title":"Kalugina, Autophagy and the integrated stress response","volume":"40","author":"Kroemer","year":"2010","journal-title":"Mol. Cell."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.3748\/wjg.v30.i11.1524","article-title":"Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases","volume":"30","author":"Chang","year":"2024","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Koukourakis, M.I., Kalamida, D., Giatromanolaki, A., Zois, C.E., Sivridis, E., Pouliliou, S., Mitrakas, A., Gatter, K.C., and Harris, A.L. (2015). Autophagosome Proteins LC3A, LC3B and LC3C Have Distinct Subcellular Distribution Kinetics and Expression in Cancer Cell Lines. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137675"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cao, Z., Tian, K., Ran, Y., Zhou, H., Zhou, L., Ding, Y., and Tang, X. (2024). Beclin-1: A therapeutic target at the intersection of auto-phagy, immunotherapy, and cancer treatment. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1506426"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Chan, W.W.R., Chow, J., Chau, D.D.-L., Zhai, Y., and Lau, K.-F. (2025). Beclin 1-Mediated Autophagy Is Potentiated by an Interaction with the Neuronal Adaptor FE65. Biology, 14.","DOI":"10.3390\/biology14010097"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1038\/s41467-022-29139-1","article-title":"LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy","volume":"13","author":"Hwang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13172","DOI":"10.3390\/ijms241713172","article-title":"Resveratrol and 2-Ethyl-6-Methyl-3-Hydroxypiridine N-Acetyl Cysteinate as Protecting Agents upon the Stress Exposure","volume":"24","author":"Zhigacheva","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"120025","DOI":"10.1016\/j.lfs.2021.120025","article-title":"L-Carnitine modulates autophagy, oxidative stress and inflammation in trazodone induced testicular toxicity","volume":"290","author":"Khedr","year":"2022","journal-title":"Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.metabol.2017.09.005","article-title":"Carnitine induces autophagy and restores high-fat diet-induced mitochondrial dysfunction","volume":"78","author":"Choi","year":"2018","journal-title":"Metabolism"},{"key":"ref_34","first-page":"94","article-title":"The effect of L-carnitine on oxidative stress in cardiovascular diseases","volume":"10","author":"Astashkin","year":"2016","journal-title":"Med. Counc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/jat.1264","article-title":"The antioxidant and pro-oxidant activity of vitamin C and trolox in vitro: A comparative study","volume":"28","author":"Poljsak","year":"2008","journal-title":"Appl. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Giordano, M.E., Caricato, R., and Lionetto, M.G. (2020). Concentration Dependence of the Antioxidant and Prooxidant Activity of Trolox in HeLa Cells: Involvement in the Induction of Apoptotic Volume Decrease. Antioxidants, 9.","DOI":"10.3390\/antiox9111058"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1021\/tx0500575","article-title":"Prooxidant and antioxidant activity of vitamin E analogues and troglitazone","volume":"18","author":"Tafazoli","year":"2005","journal-title":"Chem. Res. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"112922","DOI":"10.1016\/j.exger.2025.112922","article-title":"Antioxidant-induced autophagy ameliorates oxidative mediated endoplasmic reticulum stress in ultraviolet-B-exposed human primary dermal fibroblasts","volume":"211","author":"Ahmad","year":"2025","journal-title":"Exp. Gerontol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"214","DOI":"10.2174\/1573406412666161104122310","article-title":"Anti-inflammatory and Hypolipidemic Effect of Novel Conjugates with Trolox and Other Antioxidant Acids","volume":"13","author":"Nobelos","year":"2017","journal-title":"Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sacks, B., Onal, H., Martorana, R., Sehgal, A., Harvey, A., Wastella, C., Ahmad, H., Ross, E., Pjetergjoka, A., and Prasad, S. (2021). Mitochondrial targeted antioxidants, mitoquinone and SKQ1, not vitamin C, miti-gate doxorubicin-induced damage in H9c2 myoblast: Pretreatment vs. co-treatment. BMC Pharmacol. Toxicol., 22.","DOI":"10.1186\/s40360-021-00518-6"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100142","DOI":"10.1016\/j.arres.2025.100142","article-title":"Advancements in mitochondrial-targeted antioxidants: Organelle-specific drug delivery for disease management","volume":"17","author":"Nahar","year":"2025","journal-title":"Adv. Redox Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Plotnikov, E.Y., and Zorov, D.B. (2019). Pros and Cons of Use of Mitochondria-Targeted Antioxidants. Antioxidants, 8.","DOI":"10.3390\/antiox8080316"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s12964-019-0445-0","article-title":"Linoleic acid improves assembly of the CII subunit and CIII2\/CIV complex of the mitochondrial oxidative phosphorylation system in heart failure","volume":"17","author":"Maekawa","year":"2019","journal-title":"Cell Commun. Signal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"102774","DOI":"10.1016\/j.redox.2023.102774","article-title":"Unraveling the mechanisms of cardiolipin function: The role of oxidative polymerization of unsaturat-ed acyl chains","volume":"64","author":"Jang","year":"2023","journal-title":"Redox Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2174\/1874467215666220308115514","article-title":"Ethoxidol as a broad-spectrum adaptogen","volume":"16","author":"Zhigacheva","year":"2023","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_46","unstructured":"Council of Europe (1986). European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS No. 123), Council of Europe."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/BF02262915","article-title":"Thermodynamic evaluation interaction of fatty acid methyl esters with polar and nonpolar stationary phases, based on their retention indices chromatographia","volume":"10","author":"Golovina","year":"1977","journal-title":"Chromatography"},{"key":"ref_48","first-page":"34","article-title":"Features of interpretation of performance indicators of laboratory animals according to swimming tests with load","volume":"4","author":"Karkishchenko","year":"2016","journal-title":"Biomedicine"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8903\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:35:17Z","timestamp":1791372917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8903"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":48,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198903"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198903","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]}}}