{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T16:21:21Z","timestamp":1778170881447,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-75-10006"],"award-info":[{"award-number":["20-75-10006"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Duchenne muscular dystrophy is caused by the loss of functional dystrophin that secondarily causes systemic metabolic impairment in skeletal muscles and cardiomyocytes. The nutraceutical approach is considered as a possible complementary therapy for this pathology. In this work, we have studied the effect of pyrimidine nucleoside uridine (30 mg\/kg\/day for 28 days, i.p.), which plays an important role in cellular metabolism, on the development of DMD in the skeletal muscles of dystrophin deficient mdx mice, as well as its effect on the mitochondrial dysfunction that accompanies this pathology. We found that chronic uridine administration reduced fibrosis in the skeletal muscles of mdx mice, but it had no effect on the intensity of degeneration\/regeneration cycles and inflammation, pseudohypetrophy, and muscle strength of the animals. Analysis of TEM micrographs showed that uridine also had no effect on the impaired mitochondrial ultrastructure of mdx mouse skeletal muscle. The administration of uridine was found to lead to an increase in the expression of the Drp1 and Parkin genes, which may indicate an increase in the intensity of organelle fission and the normalization of mitophagy. Uridine had little effect on OXPHOS dysfunction in mdx mouse mitochondria, and moreover, it was suppressed in the mitochondria of wild type animals. At the same time, uridine restored the transport of potassium ions and reduced the production of reactive oxygen species; however, this had no effect on the impaired calcium retention capacity of mdx mouse mitochondria. The obtained results demonstrate that the used dose of uridine only partially prevents mitochondrial dysfunction in skeletal muscles during Duchenne dystrophy, though it mitigates the development of destructive processes in skeletal muscles.<\/jats:p>","DOI":"10.3390\/ijms231810660","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T21:06:52Z","timestamp":1663103212000},"page":"10660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Effect of Uridine on the State of Skeletal Muscles and the Functioning of Mitochondria in Duchenne Dystrophy"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7453-3390","authenticated-orcid":false,"given":"Mikhail V.","family":"Dubinin","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vlada S.","family":"Starinets","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5707-6557","authenticated-orcid":false,"given":"Natalia V.","family":"Belosludtseva","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina B.","family":"Mikheeva","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuliya A.","family":"Chelyadnikova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria K.","family":"Penkina","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.","family":"Vedernikov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-7035","authenticated-orcid":false,"given":"Konstantin N.","family":"Belosludtsev","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, Russia"},{"name":"Laboratory of Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0960-8966(91)90039-U","article-title":"Population frequencies of inherited neuromuscular diseases\u2014A world survey","volume":"1","author":"Emery","year":"1991","journal-title":"Neuromuscul. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s10654-021-00819-4","article-title":"One in five patients with Duchenne muscular dystrophy dies from other causes than cardiac or respiratory failure","volume":"37","author":"Wahlgren","year":"2022","journal-title":"Eur. J. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.mehy.2015.08.015","article-title":"Revisiting the dystrophin-ATP connection: How half a century of research still implicates mitochondrial dysfunction in duchenne muscular dystrophy aetiology","volume":"85","author":"Timpani","year":"2015","journal-title":"Med. Hypotheses"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9734","DOI":"10.3390\/nu7125498","article-title":"Metabogenic and Nutriceutical Approaches to Address Energy Dysregulation and Skeletal Muscle Wasting in Duchenne Muscular Dystrophy","volume":"7","author":"Rybalka","year":"2015","journal-title":"Nutrients"},{"key":"ref_5","first-page":"452","article-title":"Phosphorylase activity and glycogen, glucose-6-phosphate, and lactic acid content of human skeletal muscle in various myopathies","volume":"66","author":"Hess","year":"1965","journal-title":"J. Lab. Clin. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1007\/BF01921731","article-title":"Dystrophin-dependent efficiency of metabolic pathways in mouse skeletal muscles","volume":"50","author":"Chinet","year":"1994","journal-title":"Experientia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1093\/hmg\/ddy404","article-title":"Dystrophinopathy-associated dysfunction of Krebs cycle metabolism","volume":"28","author":"Lindsay","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rybalka, E., Timpani, C.A., Cooke, M.B., Williams, A.D., and Hayes, A. (2014). Defects in mitochondrial ATP synthesis in dystrophindeficient Mdx skeletal muscles may be caused by complex I insufficiency. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115763"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/jcsm.12405","article-title":"Early myopathy in Duchenne muscular dystrophy is associated with elevated mitochondrial H2O2 emission during impaired oxidative phosphorylation","volume":"10","author":"Hughes","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1038\/s41598-019-38609-4","article-title":"Reduced mitochondrial respiration and increased calcium deposits in the EDL muscle, but not in soleus, from 12-week-old dystrophic mdx mice","volume":"9","author":"Gaglianone","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"165674","DOI":"10.1016\/j.bbadis.2020.165674","article-title":"Duchenne muscular dystrophy is associated with the inhibition of calcium uniport in mitochondria and an increased sensitivity of the organelles to the calcium-induced permeability transition","volume":"1866","author":"Dubinin","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dubinin, M.V., Talanov, E.Y., Tenkov, K.S., Starinets, V.S., Belosludtseva, N.V., and Belosludtsev, K.N. (2020). The Effect of Deflazacort Treatment on the Functioning of Skeletal Muscle Mitochondria in Duchenne Muscular Dystrophy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228763"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112968","DOI":"10.1016\/j.yexcr.2021.112968","article-title":"Therapeutic approaches to preserve the musculature in Duchenne muscular dystrophy: The importance of the secondary therapies","volume":"410","author":"Angelini","year":"2022","journal-title":"Exp. Cell Res."},{"key":"ref_14","first-page":"7091718","article-title":"Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis","volume":"2020","author":"Zhang","year":"2020","journal-title":"Biomed Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0165-6147(99)01298-5","article-title":"Uridine and its nucleotides: Biological actions, therapeutic potentials","volume":"20","author":"Connolly","year":"1999","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1016\/j.cca.2011.06.006","article-title":"Biochemistry of uridine in plasma","volume":"412","author":"Yamamoto","year":"2011","journal-title":"Clin. Chim. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1194\/jlr.M034249","article-title":"Disruption of uridine homeostasis links liver pyrimidine metabolism to lipid accumulation","volume":"54","author":"Le","year":"2013","journal-title":"J. Lipid. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1136\/jnnp.26.2.111","article-title":"A trial of therapy by nucleosides and nucleotides in muscular dystrophy","volume":"26","author":"Thomson","year":"1963","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1007\/s10517-014-2653-3","article-title":"Antiarrhythmic effect of uridine and uridine-5\u2032-monophosphate in acute myocardial ischemia","volume":"157","author":"Bulon","year":"2014","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/s10517-012-1787-4","article-title":"Effect of uridine on energy metabolism, LPO, and antioxidant system in the myocardium under conditions of acute coronary insufficiency","volume":"153","author":"Krylova","year":"2012","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.exger.2006.03.005","article-title":"The cardioprotective effect of uridine and uridine-5\u2032-monophosphate: The role of the mitochondrial ATP-dependent potassium channel","volume":"41","author":"Krylova","year":"2006","journal-title":"Exp. Gerontol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16999","DOI":"10.1038\/s41598-021-96562-7","article-title":"Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia\/reperfusion by activating the mitochondrial ATP-dependent potassium channel","volume":"11","author":"Krylova","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Urasaki, Y., Pizzorno, G., and Le, T.T. (2016). Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146994"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Salera, S., Menni, F., Moggio, M., Guez, S., Sciacco, M., and Esposito, S. (2017). Nutritional Challenges in Duchenne Muscular Dystrophy. Nutrients, 9.","DOI":"10.3390\/nu9060594"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pant, M., Sopariwala, D.H., Bal, N.C., Lowe, J., Delf\u00edn, D.A., Rafael-Fortney, J., and Periasamy, M. (2015). Metabolic dysfunction and altered mitochondrial dynamics in the utrophin-dystrophin deficient mouse model of Duchenne muscular dystrophy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123875"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dubinin, M.V., Starinets, V.S., Talanov, E.Y., Mikheeva, I.B., Belosludtseva, N.V., and Belosludtsev, K.N. (2021). Alisporivir Improves Mitochondrial Function in Skeletal Muscle of mdx Mice but Suppresses Mitochondrial Dynamics and Biogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189780"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105751","DOI":"10.1016\/j.phrs.2021.105751","article-title":"Givinostat as metabolic enhancer reverting mitochondrial biogenesis deficit in Duchenne muscular dystrophy","volume":"170","author":"Giovarelli","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"32562","DOI":"10.1074\/jbc.M401115200","article-title":"Functional distinctions between the mitochondrial ATP-dependent K+ channel (mitoKATP) and its inward rectifier subunit (mitoKIR)","volume":"279","author":"Mironova","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_29","first-page":"218","article-title":"Inhibition of 2,4-dinitrophenol-induced potassium efflux by adenine nucleotides in mitochondria","volume":"65","author":"Baranova","year":"2000","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"965631","DOI":"10.1155\/2014\/965631","article-title":"Understanding the process of fibrosis in Duchenne muscular dystrophy","volume":"2014","author":"Kharraz","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_31","first-page":"565","article-title":"Effects of uridine and inosine on glucose metabolism in skeletal muscle and activated lipolysis in adipose tissue","volume":"19","author":"Kypson","year":"1976","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Urasaki, Y., Pizzorno, G., and Le, T.T. (2014). Uridine affects liver protein glycosylation, insulin signaling, and heme biosynthesis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099728"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"26062","DOI":"10.1016\/S0021-9258(18)35717-X","article-title":"Reconstitution and partial purification of the glibenclamide-sensitive, ATP-dependent K+ channel from rat liver and beef heart mitochondria","volume":"267","author":"Paucek","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41586-019-1498-3","article-title":"Identification of an ATP-sensitive potassium channel in mitochondria","volume":"572","author":"Paggio","year":"2019","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Graciotti, L., Becker, J., Granata, A.L., Procopio, A.D., Tessarollo, L., and Fulgenzi, G. (2011). Dystrophin is required for the normal function of the cardio-protective K(ATP) channel in cardiomyocytes. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027034"},{"key":"ref_36","first-page":"593","article-title":"Mitochondrial Ca2+ Transport: Mechanisms, Molecular Structures, and Role in Cells","volume":"84","author":"Belosludtsev","year":"2019","journal-title":"Biochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bonora, M., Patergnani, S., Ramaccini, D., Morciano, G., Pedriali, G., Kahsay, A.E., Bouhamida, E., Giorgi, C., Wieckowski, M.R., and Pinton, P. (2020). Physiopathology of the permeability transition pore: Molecular mechanisms in human pathology. Biomolecules, 10.","DOI":"10.3390\/biom10070998"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.phrs.2017.09.001","article-title":"Alisporivir rescues defective mitochondrial respiration in Duchenne muscular dystrophy","volume":"125","author":"Schiavone","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_39","first-page":"e2609","article-title":"Measuring motor coordination in mice","volume":"75","author":"Deacon","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ye, J., Coulouris, G., Zaretskaya, I., Cutcutache, I., Rozen, S., and Madden, T.L. (2012). Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-134"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/cpmo.21","article-title":"Analysis of mtDNA\/nDNA ratio in mice","volume":"7","author":"Quiros","year":"2017","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.biochi.2020.07.011","article-title":"Itaconic acid impairs the mitochondrial function by the inhibition of complexes II and IV and induction of the permeability transition pore opening in rat liver mitochondria","volume":"176","author":"Belosludtsev","year":"2020","journal-title":"Biochimie"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Belosludtseva, N.V., Starinets, V.S., Mikheeva, I.B., Serov, D.A., Astashev, M.E., Belosludtsev, M.N., Dubinin, M.V., and Belosludtsev, K.N. (2021). Effect of the MPT Pore Inhibitor Alisporivir on the Development of Mitochondrial Dysfunction in the Heart Tissue of Diabetic Mice. Biology, 10.","DOI":"10.3390\/biology10090839"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"148250","DOI":"10.1016\/j.bbabio.2020.148250","article-title":"Transport of Ca2+ and Ca2+-dependent permeability transition in heart mitochondria in the early stages of Duchenne muscular dystrophy","volume":"1861","author":"Dubinin","year":"2020","journal-title":"Biochim. Biophys. Acta Bioenerg."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10660\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:30:50Z","timestamp":1760142650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":45,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810660"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810660","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,13]]}}}