{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:00:04Z","timestamp":1785474004012,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"crossref","award":["MC003-65"],"award-info":[{"award-number":["MC003-65"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"crossref"}]},{"award":["MC003-65"],"award-info":[{"award-number":["MC003-65"]}],"id":[{"id":"https:\/\/ror.org\/05m2fqn25","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The clinical use of doxorubicin (DOX), an effective chemotherapeutic drug for breast cancer, is limited by off-target nephrotoxicity, which is exacerbated in elderly patients. While excessive mitochondrial fission is known to contribute to DOX-induced cardiotoxicity, its role in DOX-induced nephrotoxicity, particularly in the context of renal aging, remains unclear. To explore this and investigate the therapeutic potential of the mitochondrial fission inhibitor Mdivi-1, female Wistar rats with D-galactose-induced accelerated renal aging were allocated into four groups: vehicle, DOX, DOX+Mdivi-1 co-treatment, and DOX+Mdivi-1 post-treatment. DOX administration resulted in significant renal dysfunction, oxidative stress, inflammation, and histopathological damage. Mitochondrial dysfunction along with the increased expression of fission protein, decreased fusion proteins, and activation of apoptotic markers and PINK1 expression were also evident. Remarkably, both co-treatment and post-treatment with Mdivi-1 comparably and significantly attenuated DOX-induced renal damage. This study suggests that Mdivi-1 mitigates DOX-induced nephrotoxicity in the aged kidney by modulating mitochondrial dynamics, suppressing oxidative stress and inflammation, and inhibiting apoptosis. These findings highlight mitochondrial fission as a promising therapeutic target for the treatment of doxorubicin toxicity and provide further support for the possible use of Mdivi-1 as a therapeutic strategy to protect the kidneys of elderly breast cancer patients undergoing chemotherapy.<\/jats:p>","DOI":"10.3390\/biom16081112","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T17:01:46Z","timestamp":1785344506000},"page":"1112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Mitochondrial Fission by Mdivi-1 Alleviates Doxorubicin-Induced Nephrotoxicity in a Rat Model of D-Galactose-Induced Accelerated Renal Aging"],"prefix":"10.3390","volume":"16","author":[{"given":"Anongporn","family":"Kobroob","sequence":"first","affiliation":[{"name":"Division of Physiology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4379-8054","authenticated-orcid":false,"given":"Chayodom","family":"Maneechote","sequence":"additional","affiliation":[{"name":"Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-7193","authenticated-orcid":false,"given":"Sivaporn","family":"Sivasinprasasn","sequence":"additional","affiliation":[{"name":"School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nipon","family":"Chattipakorn","sequence":"additional","affiliation":[{"name":"Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8535-3870","authenticated-orcid":false,"given":"Orawan","family":"Wongmekiat","sequence":"additional","affiliation":[{"name":"Integrative Renal Research Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.54457\/DR.202402015","article-title":"Multifaced Anticancer Potential of Doxorubicin: Spotlight on Breast Cancer","volume":"5","author":"Swain","year":"2025","journal-title":"Dis. 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