{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T15:57:48Z","timestamp":1776700668856,"version":"3.51.2"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,8,21]],"date-time":"2006-08-21T00:00:00Z","timestamp":1156118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adriamycin (ADR), a potent anti\u2010tumor agent, produces reactive oxygen species (ROS) in cardiac tissue. Treatment with ADR is dose\u2010limited by cardiotoxicity. However, the effect of ADR in the other tissues, including the brain, is unclear because ADR does not pass the blood\u2013brain barrier. Some cancer patients receiving ADR treatment develop a transient memory loss, inability to handle complex tasks etc., often referred to by patients as chemobrain. We previously demonstrated that ADR causes CNS toxicity, in part, via systemic release of cytokines and subsequent generation of reactive oxygen and nitrogen species (RONS) in the brain. Here, we demonstrate that treatment with ADR led to an increased circulating level of tumor necrosis factor\u2010alpha in wild\u2010type mice and in mice deficient in the inducible form of nitric oxide (iNOSKO). However, the decline in mitochondrial respiration and mitochondrial protein nitration after ADR treatment was observed only in wild\u2010type mice, not in the iNOSKO mice. Importantly, the activity of a major mitochondrial antioxidant enzyme, manganese superoxide dismutase (MnSOD), was reduced and the protein was nitrated. Together, these results suggest that NO is an important mediator, coupling the effect of ADR with cytokine production and subsequent activation of iNOS expression. We also identified the mitochondrion as an important target of ADR\u2010induced NO\u2010mediated CNS injury.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.04179.x","type":"journal-article","created":{"date-parts":[[2006,11,20]],"date-time":"2006-11-20T17:17:40Z","timestamp":1164043060000},"page":"191-201","source":"Crossref","is-referenced-by-count":155,"title":["Adriamycin\u2010mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain"],"prefix":"10.1111","volume":"100","author":[{"given":"Jitbanjong","family":"Tangpong","sequence":"first","affiliation":[]},{"given":"Marsha P.","family":"Cole","sequence":"additional","affiliation":[]},{"given":"Rukhsana","family":"Sultana","sequence":"additional","affiliation":[]},{"given":"Steven","family":"Estus","sequence":"additional","affiliation":[]},{"given":"Mary","family":"Vore","sequence":"additional","affiliation":[]},{"given":"William","family":"St. Clair","sequence":"additional","affiliation":[]},{"given":"Suvina","family":"Ratanachaiyavong","sequence":"additional","affiliation":[]},{"given":"Daret K.","family":"St. Clair","sequence":"additional","affiliation":[]},{"given":"D. Allan","family":"Butterfield","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2006,8,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3816\/CBC.2002.s.018"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.2.485"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.11.7918"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00794-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-3124(08)60057-7"},{"key":"e_1_2_7_8_1","first-page":"245","article-title":"Nitric oxide and cellular stress response in brain aging and neurodegenerative disorders: the role of vitagenes","volume":"18","author":"Calabrese V.","year":"2004","journal-title":"In Vivo"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000081313"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01786.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230490502601"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.828"},{"key":"e_1_2_7_13_1","first-page":"295","article-title":"The interactions between nitric oxide and brain nerve terminals as studied by electron paramagnetic resonance","volume":"356","author":"Cooper C. E.","year":"1994","journal-title":"FEBS Lett."},{"key":"e_1_2_7_14_1","first-page":"27","article-title":"Nitric oxide and peroxynitrite cause irreversible increases in the K(m) for oxygen of mitochondrial cytochrome oxidase: in vitro and in vivo studies","volume":"17","author":"Cooper C. E.","year":"2003","journal-title":"Biochem. Biophys. Acta"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.15.11341"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1523\/JNEUROSCI.18-06-02040.1998","article-title":"Manganese superoxide dismutase protects nNOS neurons from NMDA and nitric oxide\u2010mediated neurotoxicity","volume":"18","author":"Gonzalez\u2010Zulueta M.","year":"1998","journal-title":"J. Neurosci."},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(93)90027-V"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208908"},{"key":"e_1_2_7_19_1","unstructured":"HalliwellB.andGutteridgeJ. M. C.(1999)Free Radicals In Biology and Medicine. Third Edition Oxford University Press UK."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb07820.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715760500143478"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106829200"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015976430790"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000141294.25130.54"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-02-00687.1998"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(99)00229-6"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi002312k"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9782"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(94)33040-9"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-376"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)01082-8"},{"key":"e_1_2_7_32_1","first-page":"169","article-title":"Central nervous system cytokines and their relevance for neurotoxicity and apoptosis","volume":"49","author":"Licinio J.","year":"1997","journal-title":"J. Neural Transm."},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119846"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11853"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(01)00292-5"},{"key":"e_1_2_7_36_1","first-page":"3049","article-title":"Nitric oxide production and MDR expression by human brain endothelial cells","volume":"18","author":"Mandi Y.","year":"1998","journal-title":"Anticancer Res."},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10168"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203065200"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(83)90451-3"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199312303292706"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00436.2001"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/16.1.32"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/13550280290101021"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307446101"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.055"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.9.3056"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg267"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19990201)85:3<640::AID-CNCR14>3.0.CO;2-G"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715769209079515"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007094214460"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-08-02653.1997"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20092"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(89)90192-9"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02903-1"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119807"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-004-7028-0"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.10.004"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(01)00428-2"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.02.013"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-003-0391-x"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-004-1538-5"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715769900301181"},{"key":"e_1_2_7_63_1","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/S0022-3565(24)39082-2","article-title":"Cardiac peroxynitrite formation and left ventricular dysfunction following doxorubicin treatment in mice","volume":"294","author":"Weinstein D. M.","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00925.2004"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.23.14085"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118909"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1998.1011"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03217.x"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1471-4159.2006.04179.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1471-4159.2006.04179.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T00:35:37Z","timestamp":1736642137000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1471-4159.2006.04179.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,8,21]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,1]]}},"alternative-id":["10.1111\/j.1471-4159.2006.04179.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1471-4159.2006.04179.x","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,8,21]]}}}