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However, the pathogenic mechanisms underlying doxorubicin\u2010induced atrophy of the spleen remain unclear. This study investigates that doxorubicin treatment leads to splenic atrophy through several interconnected pathways involving histological changes, an inflammatory response, and apoptosis. Immunohistochemical and western blot analyses revealed reduced size of white and red pulp, decreased cellularity, amyloidosis, and fibrotic remodeling in the spleen following doxorubicin treatment. Additionally, increased secretion of pro\u2010inflammatory cytokines was detected using an antibody array and enzyme\u2010linked immunosorbent assay (ELISA), which triggers inflammation through the regulation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor\u2010kappa B (NF\u2010\u03baB) signaling pathways. Further analysis revealed that the loss of regulators and effectors of the oxidative defense system, including sirtuin (Sirt)3, Sirt5, superoxide dismutase (SOD)1, and SOD2, was implicated in the upstream regulation of caspase\u2010dependent cellular apoptosis. These findings provide insights on the pathogenic mechanisms underlying doxorubicin\u2010induced splenic atrophy and suggest that further investigation may be warranted to explore strategies for managing potential side effects in breast cancer patients treated with doxorubicin.<\/jats:p>","DOI":"10.1002\/jat.4666","type":"journal-article","created":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T03:11:01Z","timestamp":1719630661000},"page":"1606-1615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Possible pathogenic mechanisms for doxorubicin\u2010induced splenic atrophy in a human breast cancer xenograft mouse model"],"prefix":"10.1002","volume":"44","author":[{"given":"Jianjie","family":"Xue","sequence":"first","affiliation":[{"name":"Qingdao Municipal Center for Disease Control and Prevention  Qingdao China"},{"name":"Qingdao Institute of Preventive Medicine  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Ye","sequence":"additional","affiliation":[{"name":"Qingdao Municipal Center for Disease Control and Prevention  Qingdao China"},{"name":"Qingdao Institute of Preventive Medicine  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2218-1828","authenticated-orcid":false,"given":"Mengqi","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Life Science, Changchun Sci\u2010Tech University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13010041"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986709788803312"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1016167228059"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12040823"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S150968"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7991"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.3549"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115469"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601383"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/1120009X.2019.1708153"},{"issue":"1","key":"e_1_2_8_12_1","first-page":"265","article-title":"Splenic fibrosis and sarcomas in F344 rats fed diets containing aniline hydrochloride, p\u2010chloroaniline, azobenzene, o\u2010toluidine hydrochloride, 4,4\u2032\u2010sulfonyldianiline, or D & C red no. 9","volume":"73","author":"Goodman D. 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