{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T17:53:08Z","timestamp":1777139588585,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"City of Hope National Medical Center","award":["011078"],"award-info":[{"award-number":["011078"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["011078"],"award-info":[{"award-number":["011078"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2020,10,21]]},"abstract":"<jats:p>This study investigated the effect of anthracycline antibiotics, mitomycin C, and menadione on oxygen consumption and hydrogen peroxide production by intact, beating, rat heart myocytes. Doxorubicin produced a dose-dependent increase in the rate of cyanide-resistant respiration by beating myocytes. The anthracycline analogs 4-demethoxydaunorubicin, 4<jats:inline-formula><a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><a:msup><a:mrow\/><a:mrow><a:mo>\u2032<\/a:mo><\/a:mrow><\/a:msup><\/a:math><\/jats:inline-formula>-epidoxorubicin, 4<jats:inline-formula><c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><c:msup><c:mrow\/><c:mrow><c:mo>\u2032<\/c:mo><\/c:mrow><\/c:msup><\/c:math><\/jats:inline-formula>-deoxydoxorubicin, and menogaril, as well as the anticancer quinones mitomycin C and menadione, also significantly increased oxygen consumption by cardiac myocytes. However, 5-iminodaunorubicin (which has a substituted quinone group) and mitoxantrone (which is not easily reduced by flavin dehydrogenases) had no effect on cardiac respiration. Both catalase (43%) and acetylated cytochrome c (19%) significantly decreased oxygen consumption that had been stimulated by doxorubicin; furthermore, extracellular hydrogen peroxide production was increased from undetectable control levels to<jats:inline-formula><e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><e:mn>1.30<\/e:mn><e:mo>\u00b1<\/e:mo><e:mn>0.02<\/e:mn><\/e:math><\/jats:inline-formula>\u2009nmol\/min\/107 myocytes (<jats:inline-formula><g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><g:mi>n<\/g:mi><g:mo>=<\/g:mo><g:mn>4<\/g:mn><\/g:math><\/jats:inline-formula>,<jats:inline-formula><i:math xmlns:i=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><i:mi>P<\/i:mi><i:mo>&lt;<\/i:mo><i:mn>0.01<\/i:mn><\/i:math><\/jats:inline-formula>) in the presence of 400\u2009\u03bcM doxorubicin. These experiments suggest that the anthracycline antibiotics and other anticancer quinones stimulate cardiac oxygen radical production in intact heart myocytes; such a free radical cascade could contribute to the cardiac toxicity of these drugs.<\/jats:p>","DOI":"10.1155\/2020\/8877100","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T17:35:24Z","timestamp":1603388124000},"page":"1-7","source":"Crossref","is-referenced-by-count":10,"title":["Effect of Anticancer Quinones on Reactive Oxygen Production by Adult Rat Heart Myocytes"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-1790","authenticated-orcid":true,"given":"James H.","family":"Doroshow","sequence":"first","affiliation":[{"name":"Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD 20892, USA"},{"name":"Developmental Therapeutics Branch of the Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA"},{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","first-page":"356","article-title":"Topoisomerase II inhibitors: anthracyclines","volume-title":"Cancer Chemotherapy and Biotherapy: Principles and Practice","author":"J. H. Doroshow","year":"2011","edition":"5th"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.1242"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e32803d36fe"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70204-7"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2919"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00738.2005"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-006-0069-x"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.02.060"},{"issue":"7","key":"9","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1016\/S0021-9258(17)35747-2","article-title":"Redox cycling of anthracyclines by cardiac mitochondria. II formation of superoxide anion, hydrogen peroxide, and hydroxyl radical","volume":"261","author":"J. H. Doroshow","year":"1986","journal-title":"Journal of Biological Chemistry"},{"issue":"2","key":"10","first-page":"460","article-title":"Effect of anthracycline antibiotics on oxygen radical formation in rat heart","volume":"43","author":"J. H. Doroshow","year":"1983","journal-title":"Cancer Research"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.05.027"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2008-0151"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1996.271.5.H2079"},{"key":"14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3109\/10715768809066915","article-title":"Effect of daunorubicin on subcellular pools of glutathione in cultured heart cells from neonatal rats","volume":"5","author":"D. Galaris","year":"2009","journal-title":"Free Radical Research Communications"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2019.100709"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(75)80188-4"},{"issue":"22","key":"17","first-page":"6049","article-title":"Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein)","volume":"244","author":"J. M. McCord","year":"1969","journal-title":"Journal of Biological Chemistry"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(74)90329-7"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1007\/BF00233618"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9474823"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1042\/bj0900225"},{"issue":"10","key":"22","first-page":"4543","article-title":"Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase","volume":"43","author":"J. H. Doroshow","year":"1983","journal-title":"Cancer Research"},{"key":"23","volume-title":"Statistical Methods in Medical Research","author":"P. Armitage","year":"1971","edition":"1"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2019.1641602"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(83)90399-4"},{"key":"26","first-page":"206","article-title":"Mitomycin C-enhanced superoxide and hydrogen peroxide formation in rat heart","volume":"218","author":"J. H. Doroshow","year":"1981","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"27","doi-asserted-by":"crossref","first-page":"12419","DOI":"10.1016\/S0021-9258(18)33730-X","article-title":"The metabolism of menadione (2-methyl-1, 4-naphthoquinone) by isolated hepatocytes: a study of the implications of oxidative stress in intact cells","volume":"257","author":"H. Thor","year":"1982","journal-title":"Journal of Biological Chemistry"},{"issue":"5","key":"28","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1016\/S0021-9258(18)89421-2","article-title":"Cytosolic Ca2+ homeostasis in Ehrlich and Yoshida carcinomas. A new, membrane-permeant chelator of heavy metals reveals that these ascites tumor cell lines have normal cytosolic free Ca2+","volume":"260","author":"P. Arslan","year":"1985","journal-title":"Journal of Biological Chemistry"},{"key":"29","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1021\/bi00300a021","article-title":"Oxidative destruction of DNA by the adriamycin-iron complex","volume":"23","author":"H. Eliot","year":"2002","journal-title":"Biochemistry"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(83)91157-9"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1007\/BF02934854"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.2459\/JCM.0000000000000376"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.2174\/138920112802273245"},{"issue":"1","key":"34","first-page":"218","article-title":"Comparison of adriamycin uptake in chick embryo heart and liver cells an murine L5178Y lymphoblasts in vitro: role of drug uptake in cardiotoxicity","volume":"46","author":"B. A. Johnson","year":"1986","journal-title":"Cancer Research"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2020\/8877100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2020\/8877100.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2020\/8877100.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,10]],"date-time":"2021-04-10T00:45:31Z","timestamp":1618015531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/omcl\/2020\/8877100\/"}},"subtitle":[],"editor":[{"given":"Eleonora","family":"Cianflone","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,10,21]]},"references-count":34,"alternative-id":["8877100","8877100"],"URL":"https:\/\/doi.org\/10.1155\/2020\/8877100","relation":{},"ISSN":["1942-0994","1942-0900"],"issn-type":[{"value":"1942-0994","type":"electronic"},{"value":"1942-0900","type":"print"}],"subject":[],"published":{"date-parts":[[2020,10,21]]}}}