Effect of Anticancer Quinones on Reactive Oxygen Production by Adult Rat Heart Myocytes.
Effect of Anticancer Quinones on Reactive Oxygen Production by Adult Rat Heart Myocytes.
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DOI：
10.1155/2020/8877100
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发表时间：
2020
影响因子：
--
通讯作者：
Doroshow JH
中科院分区：
文献类型：
--
作者：
Doroshow JH
本研究探讨蒽环类抗生素，丝裂霉素C，甲萘醌对氧消耗和过氧化氢的生产完整，跳动，大鼠心肌细胞的影响。多柔比星通过跳动的肌细胞产生抗氰化物呼吸速率的剂量依赖性增加。蒽环类抗生素类似物4-去甲氧基柔红霉素、4′-表阿霉素、4′-脱氧阿霉素和menogaril，以及抗癌醌丝裂霉素C和甲萘醌，也显著增加心肌细胞的耗氧量。然而，5-亚氨基柔红霉素（具有取代的醌基）和米托蒽醌（不易被黄素还原酶还原）对心脏呼吸没有影响。过氧化氢酶（43%）和乙酰化细胞色素c（19%）均显著降低阿霉素刺激的耗氧量;此外，在400 μM阿霉素存在下，细胞外过氧化氢产生从不可检测的对照水平增加至1.30 ± 0.02 nmol/min/107个心肌细胞（n = 4，P < 0.01）。这些实验表明，蒽环类抗生素和其他抗癌醌类刺激完整心肌细胞中的心脏氧自由基产生;这种自由基级联反应可能导致这些药物的心脏毒性。
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′-epidoxorubicin, 4′-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 1.30 ± 0.02 nmol/min/107 myocytes (n = 4, P < 0.01) in the presence of 400 μM 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.
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影响因子：
45.3
作者：
Hershman, Dawn L.;McBride, Russell B.;Jacobson, Judith S.
通讯作者：
Jacobson, Judith S.
影响因子：
4.1
作者：
CHAPPELL, JB
通讯作者：
CHAPPELL, JB
影响因子：
3
作者：
Madeddu, Clelia;Deidda, Martino;Mercuro, Giuseppe
通讯作者：
Mercuro, Giuseppe
影响因子：
51.1
作者：
Lipshultz, Steven E.;Scully, Rebecca E.;Lipsitz, Stuart R.;Sallan, Stephen E.;Silverman, Lewis B.;Miller, Tracie L.;Borry, Elly V.;Asselin, Barbara L.;Athale, Uma;Clavell, Luis A.;Larsen, Eric;Moghrabi, Albert;Samson, Yvan;Michon, Bruno;Schorin, Marshall A.;Cohen, Harvey J.;Neuberg, Donna S.;Orav, E. John;Colan, Steven D.
通讯作者：
Colan, Steven D.
影响因子：
5.8
作者：
Mantovani, Giovanni;Madeddu, Clelia;Mercuro, Giuseppe
通讯作者：
Mercuro, Giuseppe