{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:04:28Z","timestamp":1790291068910,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T00:00:00Z","timestamp":1610150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ortho Corporation","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Strenuous exercise induces organ damage, inflammation, and oxidative stress. Currently, to monitor or investigate physiological conditions, blood biomarkers are frequently used. However, blood sampling is perceived to be an invasive method and may induce stress. Therefore, it is necessary to establish a non-invasive assessment method that reflects physiological conditions. In the present study, we aimed to search for useful biomarkers of organ damage, inflammation, oxidative stress, and bone turnover in urine following exercise. Ten male runners participated in this study and performed a 3000-m time trial. We measured biomarkers in urine collected before and immediately after exercise. Renal damage markers such as urea protein, albumin, N-acetyl-\u03b2-D-glucosaminidase (NAG), and liver-fatty acid binding protein (L-FABP), and an intestinal damage marker, intestine-fatty acid binding protein (I-FABP), increased following exercise (p &lt; 0.05). However, a muscle damage marker, titin N-terminal fragments, did not change (p &gt; 0.05). Inflammation-related factors (IRFs), such as interleukin (IL)-1\u03b2, IL-1 receptor antagonist (IL-1ra), IL-6, complement (C) 5a, myeloperoxidase (MPO), calprotectin, monocyte chemoattractant protein (MCP)-1, and macrophage colony-stimulating factor (M-CSF), increased whereas IRFs such as IL-4 and IL-10 decreased following exercise (p &lt; 0.05). IRFs such as tumor necrosis factor (TNF)-\u03b1, IL-2, IL-8, IL-12p40, and interferon (IFN)-\u03b3 did not change (p &gt; 0.05). Oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and nitrotyrosine, did not change following exercise (p &gt; 0.05) whereas 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG) decreased (p &lt; 0.05). Bone resorption markers, such as cross-linked N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD), did not change following exercise (p &gt; 0.05). These results suggest that organ damage markers and IRFs in urine have the potential to act as non-invasive indicators to evaluate the effects of exercise on organ functions.<\/jats:p>","DOI":"10.3390\/antiox10010079","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T19:55:56Z","timestamp":1610308556000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Changes in Urinary Biomarkers of Organ Damage, Inflammation, Oxidative Stress, and Bone Turnover Following a 3000-m Time Trial"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8284-7966","authenticated-orcid":false,"given":"Takaki","family":"Tominaga","sequence":"first","affiliation":[{"name":"Graduate School of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan"},{"name":"Research Fellow of Japan Society for the Promotion of Sciences, Tokyo 102-0083, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0606-5759","authenticated-orcid":false,"given":"Sihui","family":"Ma","sequence":"additional","affiliation":[{"name":"Research Fellow of Japan Society for the Promotion of Sciences, Tokyo 102-0083, Japan"},{"name":"Faculty of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Sugama","sequence":"additional","affiliation":[{"name":"Future Innovation Institute, Waseda University, Shinjuku 162-0041, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazue","family":"Kanda","sequence":"additional","affiliation":[{"name":"Future Innovation Institute, Waseda University, Shinjuku 162-0041, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiaki","family":"Omae","sequence":"additional","affiliation":[{"name":"Graduate School of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonjun","family":"Choi","sequence":"additional","affiliation":[{"name":"Graduate School of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Ortho Corporation, Shibuya 150-0002, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Ortho Corporation, Shibuya 150-0002, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunobu","family":"Yoshikai","sequence":"additional","affiliation":[{"name":"Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6572-5809","authenticated-orcid":false,"given":"Katsuhiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Faculty of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,9]]},"reference":[{"key":"ref_1","first-page":"116","article-title":"IL-17, neutrophil activation and muscle damage following endurance exercise","volume":"18","author":"Sugama","year":"2012","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_2","first-page":"29","article-title":"Urinary excretion of cytokines versus their plasma levels after endurance exercise","volume":"19","author":"Sugama","year":"2013","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_3","first-page":"130","article-title":"Changes of thioredoxin, oxidative stress markers, inflammation and muscle\/renal damage following intensive endurance exercise","volume":"21","author":"Sugama","year":"2015","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1249\/01.MSS.0000048861.57899.04","article-title":"Impact of a competitive marathon race on systemic cytokine and neutrophil responses","volume":"35","author":"Suzuki","year":"2003","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00421-006-0296-4","article-title":"Changes in markers of muscle damage, inflammation and HSP70 after an Ironman Triathlon race","volume":"98","author":"Suzuki","year":"2006","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Suzuki, K., Tominaga, T., Ruhee, R.T., and Ma, S. (2020). Characterization and modulation of systemic inflammatory response to exhaustive exercise in relation to oxidative stress. Antioxidants, 9.","DOI":"10.3390\/antiox9050401"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"van Wijck, K., Lenaerts, K., van Loon, L.J.C., Peters, W.H.M., Buurman, W.A., and Dejong, C.H.C. (2011). Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022366"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2423(08)00401-0","article-title":"Chapter 1 Effect of exercise on oxidative stress biomarkers","volume":"Volume 46","author":"Bloomer","year":"2008","journal-title":"Advances in Clinical Chemistry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.jnutbio.2006.10.005","article-title":"The influence of antioxidant supplementation on markers of inflammation and the relationship to oxidative stress after exercise","volume":"18","author":"Peake","year":"2007","journal-title":"J. Nutr. Biochem."},{"key":"ref_10","first-page":"6","article-title":"Systemic inflammatory response to exhaustive exercise. Cytokine kinetics","volume":"8","author":"Suzuki","year":"2002","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_11","first-page":"622","article-title":"Effect of a sports drink based on highly-branched cyclic dextrin on cytokine responses to exhaustive endurance exercise","volume":"54","author":"Suzuki","year":"2014","journal-title":"J. Sports Med. Phys. Fit."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1097\/mss.0b013e3180398f4b","article-title":"Cytokine and oxidative responses to maximal cycling exercise in sedentary subjects","volume":"39","author":"Steinberg","year":"2007","journal-title":"Med Sci Sports Exerc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1080\/13510002.2016.1169622","article-title":"Effect of maximal-intensity exercise on systemic nitro-oxidative stress in men and women","volume":"22","author":"Wiecek","year":"2017","journal-title":"Redox Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S167","DOI":"10.1055\/s-2007-1021132","article-title":"The cytokine response to strenuous exercise","volume":"15","author":"Northoff","year":"1994","journal-title":"Int. J. Sports Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1053\/j.ajkd.2017.01.045","article-title":"Kidney injury and repair biomarkers in marathon runners","volume":"70","author":"Mansour","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/0090-1229(92)90012-D","article-title":"Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running","volume":"63","author":"Sprenger","year":"1992","journal-title":"Clin. Immunol. Immunopathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1097\/00005768-199703000-00009","article-title":"Effect of exhaustive exercise stress on the cytokine response","volume":"29","author":"Weinstock","year":"1997","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1080\/10715760400013763","article-title":"Evaluation of a multi-parameter biomarker set for oxidative damage in man: Increased urinary excretion of lipid, protein and DNA oxidation products after one hour of exercise","volume":"38","author":"Orhan","year":"2004","journal-title":"Free Radic. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.23937\/2469-5718\/1510122","article-title":"Characterization of exercise-induced cytokine release, the impacts on the body, the mechanisms and modulations","volume":"5","author":"Suzuki","year":"2019","journal-title":"Int. J. Sports Exerc. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1586\/14789450.2015.1094380","article-title":"Physiological conditions can be reflected in human urine proteome and metabolome","volume":"12","author":"Wu","year":"2015","journal-title":"Expert Rev. Proteom."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kanda, K., Sakuma, J., Akimoto, T., Kawakami, Y., and Suzuki, K. (2017). Detection of titin fragments in urine in response to exercise-induced muscle damage. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181623"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.jsams.2019.12.023","article-title":"Changes in urinary titin N-terminal fragments as a biomarker of exercise-induced muscle damage in the repeated bout effect","volume":"23","author":"Yamaguchi","year":"2020","journal-title":"J. Sci. Med. Sport"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.7600\/jpfsm.9.21","article-title":"N-terminal fragments of titin in urine as a biomarker for eccentric exercise-induced muscle damage","volume":"9","author":"Yamaguchi","year":"2020","journal-title":"J. Phys. Fit. Sports Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"754","DOI":"10.7326\/0003-4819-113-10-754","article-title":"Low bone density is an etiologic factor for stress fractures in athletes","volume":"113","author":"Myburgh","year":"1990","journal-title":"Ann Intern Med"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"697","DOI":"10.2165\/11533090-000000000-00000","article-title":"Bone metabolism markers in sports medicine","volume":"40","author":"Banfi","year":"2010","journal-title":"Sports Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ma, S., Tominaga, T., Kanda, K., Sugama, K., Omae, C., Hashimoto, S., Aoyama, K., Yoshikai, Y., and Suzuki, K. (2020). Effects of an 8-week protein supplementation regimen with hyperimmunized cow milk on exercise-induced organ damage and inflammation in male runners: A randomized, placebo controlled, cross-over study. Biomedicines, 8.","DOI":"10.3390\/biomedicines8030051"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/jcla.21579","article-title":"Moderate-intensity single exercise session does not induce renal damage","volume":"27","author":"Hiraki","year":"2013","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_29","first-page":"39","article-title":"Evaluation of serum leaking enzymes and investigation into new biomarkers for exercise-induced muscle damage","volume":"20","author":"Kanda","year":"2014","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/sms.13618","article-title":"Incremental short maximal exercise increases urinary liver-type fatty acid-binding protein in adults without CKD","volume":"30","author":"Kosaki","year":"2020","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/apt.14157","article-title":"Systematic review: Exercise-induced gastrointestinal syndrome-implications for health and intestinal disease","volume":"46","author":"Costa","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.7754\/Clin.Lab.2014.140518","article-title":"Intestinal fatty acid binding protein (I-FABP) as a promising test for Crohn\u2019s disease: A preliminary study","volume":"61","author":"Sarikaya","year":"2015","journal-title":"Clin. Lab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jss.2016.07.017","article-title":"Urine intestinal fatty acid-binding protein predicts acute mesenteric ischemia in patients","volume":"209","author":"Salim","year":"2017","journal-title":"J. Surg. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.pharmtox.48.113006.094615","article-title":"Biomarkers of acute kidney injury","volume":"48","author":"Vaidya","year":"2008","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2165\/00007256-199418060-00006","article-title":"Kidney function during exercise in healthy and diseased humans. An update","volume":"18","author":"Poortmans","year":"1994","journal-title":"Sports Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1249\/MSS.0000000000000555","article-title":"Response of bone turnover barkers and cytokines to high-intensity low-impact exercise","volume":"47","author":"Mezil","year":"2015","journal-title":"Med Sci Sports Exerc."},{"key":"ref_37","first-page":"154","article-title":"Bone turnover response to acute exercise with varying impact levels: A preliminary investigation","volume":"8","author":"Morgan","year":"2015","journal-title":"Int. J. Exerc. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1152\/jappl.1997.83.4.1159","article-title":"A bout of resistance exercise increases urinary calcium independently of osteoclastic activation in men","volume":"83","author":"Ashizawa","year":"1997","journal-title":"J. Appl. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s002239900402","article-title":"Effects of a single bout of resistance exercise on calcium and bone metabolism in untrained young males","volume":"62","author":"Ashizawa","year":"1998","journal-title":"Calcif. Tissue Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1055\/s-2005-837621","article-title":"The intensity level of physical exercise and the bone metabolism response","volume":"27","author":"Manetta","year":"2006","journal-title":"Int. J. Sports Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1210\/jc.2009-2516","article-title":"The effect of training status on the metabolic response of bone to an acute bout of exhaustive treadmill running","volume":"95","author":"Scott","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1113\/jphysiol.1971.sp009390","article-title":"Experiments on the liberation of phosphate from the muscles of the human forearm during vigorous exercise and on the action of sodium phosphate on forearm muscle blood vessels","volume":"213","author":"Barcroft","year":"1971","journal-title":"J. Physiol."},{"key":"ref_43","first-page":"72","article-title":"Eccentric exercise-induced delayed-onset muscle soreness and changes in markers of muscle damage and inflammation","volume":"19","author":"Kanda","year":"2013","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.2215\/CJN.02490311","article-title":"Urinary calprotectin and the distinction between prerenal and intrinsic acute kidney injury","volume":"6","author":"Heller","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1152\/physrev.2000.80.3.1107","article-title":"Creatine and creatinine metabolism","volume":"80","author":"Wyss","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bongers, C.C.W.G., Alsady, M., Nijenhuis, T., Hartman, Y.A.W., Eijsvogels, T.M.H., Deen, P.M.T., and Hopman, M.T.E. (2017). Impact of acute versus repetitive moderate intensity endurance exercise on kidney injury markers. Physiol. Rep., 5.","DOI":"10.14814\/phy2.13544"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e13734","DOI":"10.14814\/phy2.13734","article-title":"Impact of acute versus prolonged exercise and dehydration on kidney function and injury","volume":"6","author":"Bongers","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1152\/japplphysiol.01032.2018","article-title":"Impact of exercise-induced hypohydration on gastrointestinal integrity, function, symptoms, and systemic endotoxin and inflammatory profile","volume":"126","author":"Costa","year":"2019","journal-title":"J. Appl. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3177\/jnsv.59.206","article-title":"The effects of sports drink osmolality on fluid intake and immunoendocrine responses to cycling in hot conditions","volume":"59","author":"Suzuki","year":"2013","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1152\/japplphysiol.00301.2010","article-title":"Heat stroke: Role of the systemic inflammatory response","volume":"109","author":"Leon","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"376","DOI":"10.4172\/0974-8369.1000376","article-title":"Systemic inflammation mediates the effects of endotoxemia in the mechanisms of heat stroke","volume":"9","author":"Lim","year":"2017","journal-title":"Biol. Med."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/1\/79\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:08:57Z","timestamp":1760159337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/1\/79"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,9]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["antiox10010079"],"URL":"https:\/\/doi.org\/10.3390\/antiox10010079","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,9]]}}}