{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:59:12Z","timestamp":1788742752998,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. Objectives: This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-organ toxicity, to characterize their mechanisms of action and organ targets, and to identify evidence gaps and agents with translational potential. Methods: The review was designed and reported in accordance with the PRISMA-ScR checklist. A structured electronic search was conducted across PubMed\/MEDLINE, Scopus, Cochrane Library and Embase, and Web of Science from database inception to 15 July 2025. Eligible studies were restricted to full-text, peer-reviewed, English-language research involving in vivo mammalian models administered cytarabine as the principal toxin, with at least one pharmacological co-intervention and at least one quantitative or histopathological organ-injury outcome. Results: From 5701 retrieved records, 36 eligible in vivo mammalian studies (spanning 1964\u20132024) were identified. Included studies addressed neurotoxicity (n = 6), gastrointestinal mucositis (n = 9), ocular toxicity (n = 3), hepatotoxicity (n = 3), bone marrow suppression (n = 4), chemotherapy-induced alopecia (n = 5), and reproductive and developmental toxicity (n = 4). Five recurring mechanistic strategies were identified across the heterogeneous agents tested: redox buffering (N-acetylcysteine, \u03b1-lipoic acid, rutin, swertiamarin, \u03b1-tocopherol), mitochondrial preservation (betanin, thymoquinone, vitamin D, sodium zinc dihydrolipoylhistidinate [DHLHZn]), tissue-microenvironment reprogramming (apraglutide, BADGE, plerixafor, short-chain fatty acids, \u03b2-glucan), molecular antagonism (deoxycytidine, dCMP), and immunomodulation (lienal peptide, IL-1\u03b2, AHCC). Conclusions: This scoping review provides the first systematic cartography of pharmacological mitigation strategies for cytarabine-induced multi-organ toxicity. Five mechanistic pathways converge across eight organ systems, with apraglutide and N-acetylcysteine representing the most clinically translatable candidates. Plerixafor and PPAR\u03b3 blockade by BADGE constitute high-priority candidates for bone marrow niche protection, while the deoxycytidine antagonism principle warrants formal pharmacokinetic evaluation. The complete absence of cardiotoxicity mitigation data defines the most critical gap for future research.<\/jats:p>","DOI":"10.3390\/cancers18132060","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T08:14:12Z","timestamp":1782375252000},"page":"2060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological Strategies for Mitigating Cytarabine-Induced Multi-Organ Toxicity: A Scoping Review on Mechanisms, Efficacy and Clinical Implications"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1632-821X","authenticated-orcid":false,"given":"Ioannis","family":"Konstantinidis","sequence":"first","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1703-6980","authenticated-orcid":false,"given":"Sophia","family":"Tsokkou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-7480","authenticated-orcid":false,"given":"Kali","family":"Makedou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, School of Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-8208","authenticated-orcid":false,"given":"Eleni","family":"Gavriilaki","sequence":"additional","affiliation":[{"name":"Haematology Unit, Haemophilia Centre of Northern Greece, 2nd Propedeutic Department of Internal Medicine, Hippokration General Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4900-8911","authenticated-orcid":false,"given":"Georgios","family":"Delis","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-5407","authenticated-orcid":false,"given":"Theodora","family":"Papamitsou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Di Francia, R., Crisci, S., De Monaco, A., Cafiero, C., Re, A., Iaccarino, G., De Filippi, R., Frigeri, F., Corazzelli, G., and Micera, A. 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