{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T11:00:54Z","timestamp":1774868454214,"version":"3.50.1"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU\/kg), Vitamin D (60,000 IU\/kg), Doxorubicin, DOX + Vitamin D (5000 IU\/kg), and DOX + Vitamin D (60,000 IU\/kg). Vitamin D3 (cholecalciferol) was administered orally either as a daily dose (5000 IU\/kg for 12 days) or as a single bolus dose (60,000 IU\/kg). Doxorubicin (6 mg\/kg\/day, cumulative dose 18 mg\/kg) was administered intraperitoneally on days 10\u201312. Hepatic injury was evaluated using 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-\u03b1, IL-6, IL-1\u03b2, IL-10). Results: Doxorubicin markedly increased hepatic 99mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-\u03b1, IL-6, and IL-1\u03b2 levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p &lt; 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 \u00b1 2.7 vs. 74.1 \u00b1 3.8 and 69.3 \u00b1 3.2 ng\/mL for the 5000 and 60,000 IU\/kg groups, respectively; p &lt; 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, 99mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses.<\/jats:p>","DOI":"10.3390\/nu18071097","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T09:57:24Z","timestamp":1774864644000},"page":"1097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effects of Vitamin D Against Doxorubicin Chemotherapy\u2013Induced Hepatotoxicity in Wistar Albino Rats: Evidence from 99mTc-Pyrophosphate Scintigraphy and Oxidative\u2013Inflammatory Pathways"],"prefix":"10.3390","volume":"18","author":[{"given":"Murat","family":"Kal\u0131n","sequence":"first","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haluk Kerim","family":"Karakullukcu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mina","family":"Karakullukcu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aylin","family":"Arslan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Istanbul Prof. Dr. Cemil Ta\u015f\u00e7\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34668, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serdar Sava\u015f","family":"G\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Medicine, Lokman Hekim University, Ankara 06530, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reyhan","family":"Toyran","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Istanbul Sultan 2. Abdulhamid Han Training and Research Hospital, \u0130stanbul 34668, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6mer Faruk","family":"\u00d6zkan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcl\u00e7in","family":"Ercan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4272-0562","authenticated-orcid":false,"given":"Hatice","family":"Aygun","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory, BAMER, Biruni University, Istanbul 34010, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/FPC.0b013e32833ffb56","article-title":"Doxorubicin pathways: Pharmacodynamics and adverse effects","volume":"21","author":"Thorn","year":"2011","journal-title":"Pharmacogenetics Genom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.biopha.2018.02.055","article-title":"Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it","volume":"100","author":"Li","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"117455","DOI":"10.1016\/j.taap.2025.117455","article-title":"NLRP3 inflammasome regulates doxorubicin-induced cardiotoxicity by modulating the abundance of gut microbiota","volume":"502","author":"Yin","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.lfs.2018.03.023","article-title":"Toxicity of Doxorubicin (Dox) to different experimental organ systems","volume":"200","author":"Pugazhendhi","year":"2018","journal-title":"Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.pathophys.2015.04.002","article-title":"Effect of olive leaf extract treatment on doxorubicin-induced cardiac, hepatic and renal toxicity in rats","volume":"22","author":"Kumral","year":"2015","journal-title":"Pathophysiology"},{"key":"ref_7","first-page":"273","article-title":"Protective effect of pravastatin on doxorubicin-induced hepatotoxicity","volume":"118","author":"Mansouri","year":"2017","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.tox.2004.12.003","article-title":"Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats: The effects of vitamin E and catechin","volume":"209","author":"Kalender","year":"2005","journal-title":"Toxicology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/19390211.2017.1335822","article-title":"Ameliorative effect of gallic acid in doxorubicin-induced hepatotoxicity in Wistar rats through antioxidant defense system","volume":"15","author":"Omobowale","year":"2018","journal-title":"J. Diet. Suppl."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Asensio-L\u00f3pez, M.C., Soler, F., Pascual-Figal, D., Fern\u00e1ndez-Belda, F., and Lax, A. (2017). Doxorubicin-induced oxidative stress: The protective effect of nicorandil on HL-1 cardiomyocytes. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172803"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/ame2.12230","article-title":"A review: Systematic research approach on toxicity model of liver and kidney in laboratory animals","volume":"5","author":"Abbasnezhad","year":"2022","journal-title":"Anim. Models Exp. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1053\/jhep.2003.50176","article-title":"The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells","volume":"37","author":"Demers","year":"2003","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1210\/er.2008-0004","article-title":"Vitamin D and human health: Lessons from vitamin D receptor null mice","volume":"29","author":"Bouillon","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1210\/er.2012-1000","article-title":"The nonskeletal effects of vitamin D: An Endocrine Society scientific statement","volume":"33","author":"Rosen","year":"2012","journal-title":"Endocr. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1038\/s41598-018-23258-w","article-title":"Vitamin D Alleviates Lead Induced Renal and Testicular Injuries by Immunomodulatory and Antioxidant Mechanisms in Rats","volume":"8","author":"BaSalamah","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1586\/17512433.2013.841078","article-title":"Hepatic actions of vitamin D receptor ligands: A sunshine option for chronic liver disease?","volume":"6","author":"Ding","year":"2013","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e20296","DOI":"10.1097\/MD.0000000000020296","article-title":"The effect of vitamin D supplementation on the progression of fibrosis in patients with chronic liver disease: A protocol for a systematic review and meta-analysis","volume":"99","author":"Chen","year":"2020","journal-title":"Medicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1111\/ahe.12735","article-title":"Therapeutic effects of thymoquinone in doxorubicin-induced hepatotoxicity via oxidative stress, inflammation and apoptosis","volume":"50","author":"Akin","year":"2021","journal-title":"Anat. Histol. Embryol."},{"key":"ref_19","first-page":"550","article-title":"Localization of Tc-99m-pyrophosphate in the liver due to massive liver necrosis: Case report","volume":"18","author":"Lyons","year":"1977","journal-title":"J. Nucl. Med. Off. Publ. Soc. Nucl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s41110-018-0065-2","article-title":"Vitamin d3 suppresses the early stages of chemically induced hepatocarcinogenesis in rats: A dose-response analysis","volume":"43","author":"Tablas","year":"2018","journal-title":"Nutrire"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1139\/cjpp-2014-0323","article-title":"Vitamin D improves corticosteroid efficacy and attenuates its side-effects in an animal model of asthma","volume":"93","author":"Mehta","year":"2015","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1177\/0960327120950010","article-title":"Evaluation of the protective effect of paricalcitol and vitamin D3 at doxorubicin nephrotoxicity in rats with 99mTechnetium-dimercaptosuccinic acid renal scintigraphy and biochemical methods","volume":"40","author":"Demir","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103308","DOI":"10.1016\/j.sjbs.2022.103308","article-title":"Doxorubicin-induced hepatic toxicity in rats: Mechanistic protective role of Omega-3 fatty acids through Nrf2\/HO-1 activation and PI3K\/Akt\/GSK-3\u03b2 axis modulation","volume":"29","author":"Saleh","year":"2022","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10125","DOI":"10.1007\/s00210-025-03808-6","article-title":"Febuxostat protects from Doxorubicin induced hepatotoxicity in rats via regulation of NF-\u03baB p65\/NLRP3 inflammasome and SIRT-1\/AMPK pathways","volume":"398","author":"Yousef","year":"2025","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6604","DOI":"10.1038\/s41598-025-91133-6","article-title":"Mitigating doxorubicin-induced hepatotoxicity in male rats: The role of aerobic interval training and curcumin supplementation in reducing oxidative stress, endoplasmic reticulum stress and apoptosis","volume":"15","author":"Zobeydi","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1097\/00003072-199107000-00006","article-title":"Diffuse 99mTc-PYP uptake in liver due to cocaine-induced hepatotoxic necrosis (first reported case)","volume":"16","author":"Whitten","year":"1991","journal-title":"Clin. Nucl. Med."},{"key":"ref_27","first-page":"1390","article-title":"Technetium-99m-medronate uptake in hepatic necrosis associated with Budd-Chiari syndrome","volume":"33","author":"Parker","year":"1992","journal-title":"J. Nucl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature00858","article-title":"Release of chromatin protein HMGB1 by necrotic cells triggers inflammation","volume":"418","author":"Scaffidi","year":"2002","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s10020-021-00325-z","article-title":"CD36 deficiency ameliorates drug-induced acute liver injury in mice","volume":"27","author":"Zhang","year":"2021","journal-title":"Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Arab, H.H., Eid, A.H., Alsufyani, S.E., Ashour, A.M., Alnefaie, A.M., Alsharif, N.M., Alshehri, A.M., Almalawi, A.A., Alsowat, A.A., and Abd El Aal, H.A. (2024). Activation of AMPK\/mTOR-Driven Autophagy and Suppression of the HMGB1\/TLR4 Pathway with Pentoxifylline Attenuates Doxorubicin-Induced Hepatic Injury in Rats. Pharmaceuticals, 17.","DOI":"10.3390\/ph17060681"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1084\/jem.20042614","article-title":"The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion","volume":"201","author":"Tsung","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"748524","DOI":"10.1155\/2014\/748524","article-title":"Nrf2 deficiency exaggerates doxorubicin-induced cardiotoxicity and cardiac dysfunction","volume":"2014","author":"Li","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mirzaei, S., Zarrabi, A., Hashemi, F., Zabolian, A., Saleki, H., Azami, N., Hamzehlou, S., Farahani, M.V., Hushmandi, K., and Ashrafizadeh, M. (2021). Nrf2 signaling pathway in chemoprotection and doxorubicin resistance: Potential application in drug discovery. Antioxidants, 10.","DOI":"10.3390\/antiox10030349"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Soltani Hekmat, A., Hekmat, M., Ramezanipour, S., and Javanmardi, K. (2025). Protective effects of Alamandine against doxorubicin-induced liver injury in rats. BMC Pharmacol. Toxicol., 26.","DOI":"10.1186\/s40360-025-00932-0"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Radeva, L., and Yoncheva, K. (2025). Doxorubicin toxicity and recent approaches to alleviating its adverse effects with focus on oxidative stress. Molecules, 30.","DOI":"10.3390\/molecules30153311"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8296451","DOI":"10.1155\/2018\/8296451","article-title":"Protective effect of boswellic acids against doxorubicin-induced hepatotoxicity: Impact on Nrf2\/HO-1 defense pathway","volume":"2018","author":"Barakat","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2710607","DOI":"10.1155\/2022\/2710607","article-title":"Rutin and quercetin counter doxorubicin-induced liver toxicity in wistar rats via their modulatory effects on inflammation, oxidative stress, apoptosis, and Nrf2","volume":"2022","author":"Ahmed","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"102182","DOI":"10.1016\/j.tice.2023.102182","article-title":"Antioxidant and anti-inflammatory potential of crocin on the doxorubicin mediated hepatotoxicity in Wistar rats","volume":"84","author":"Demir","year":"2023","journal-title":"Tissue Cell"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Saha, S., Buttari, B., Panieri, E., Profumo, E., and Saso, L. (2020). An overview of Nrf2 signaling pathway and its role in inflammation. Molecules, 25.","DOI":"10.3390\/molecules25225474"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.taap.2016.01.006","article-title":"Inflammatory mediators in a short-time mouse model of doxorubicin-induced cardiotoxicity","volume":"293","author":"Pecoraro","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1042\/BST20140279","article-title":"Vitamin D: A custodian of cell signalling stability in health and disease","volume":"43","author":"Berridge","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wimalawansa, S.J. (2019). Vitamin D deficiency: Effects on oxidative stress, epigenetics, gene regulation, and aging. Biology, 8.","DOI":"10.3390\/biology8020030"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1007\/s12011-023-03957-w","article-title":"Calcitriol Inhibits NaAsO2 Triggered Hepatic Stellate Cells Activation and Extracellular Matrix Oversecretion by Activating Nrf2 Signaling Pathway Through Vitamin D Receptor","volume":"202","author":"Wang","year":"2024","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1210\/endrev\/bnae009","article-title":"Consensus statement on vitamin D status assessment and supplementation: Whys, whens, and hows","volume":"45","author":"Giustina","year":"2024","journal-title":"Endocr. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.1210\/jc.2017-01187","article-title":"Vitamin D stored in fat tissue during a 5-year intervention affects serum 25-hydroxyvitamin D levels the following year","volume":"102","author":"Martinaityte","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"341","DOI":"10.4158\/EP13265.RA","article-title":"Large, single-dose, oral vitamin D supplementation in adult populations: A systematic review","volume":"20","author":"Kearns","year":"2014","journal-title":"Endocr. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.toxrep.2023.11.005","article-title":"Nephroprotective effects of diminazene on doxorubicin-induced acute kidney injury in rats","volume":"11","author":"Suleimani","year":"2023","journal-title":"Toxicol. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1359\/jbmr.080903","article-title":"Analysis of CYP27B1, encoding 25-hydroxyvitamin D-1alpha-hydroxylase, as a candidate tumor suppressor gene in primary and severe secondary\/tertiary hyperparathyroidism","volume":"24","author":"Lauter","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1053\/j.ajkd.2024.03.025","article-title":"Vitamin D Metabolites Before and After Kidney Transplantation in Patients Who Are Anephric","volume":"84","author":"Billen","year":"2024","journal-title":"Am. J. Kidney Dis. Off. J. Natl. Kidney Found."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e181763","DOI":"10.1172\/jci.insight.181763","article-title":"Spatial detection and consequences of nonrenal calcitriol production as assessed by targeted mass spectrometry imaging","volume":"9","author":"Meyer","year":"2024","journal-title":"JCI Insight"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"83421","DOI":"10.1007\/s11356-023-28146-z","article-title":"Ceratonia siliqua pods (Carob) methanol extract alleviates doxorubicin-induced nephrotoxicity via antioxidant, anti-inflammatory and anti-apoptotic pathways in rats","volume":"30","author":"Atta","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_52","first-page":"e00636","article-title":"Prevention of doxorubicin-induced dyslipidaemia, plasma oxidative stress and electrolytes imbalance in Wistar rats by aqueous leaf-extracts of Chromolaena odorata and Tridax procumbens","volume":"11","author":"Ifeanacho","year":"2021","journal-title":"Sci. Afr."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Arozal, W., Eziefule, O.M., Wanandi, S.I., Louisa, M., Dewi, S., Siregar, N.C., and Makambwa, E. (2025). Doxorubicin-induced nephrotoxicity: The protective role of a standardized ethanolic extract of Andrographis paniculata leaves. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1585965"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ibiod.2015.04.021","article-title":"Toxicity of cholecalciferol to lesser bandicoot rat, Bandicota bengalensis: Biochemical and histopathological changes","volume":"103","author":"Singla","year":"2015","journal-title":"Int. Biodeterior. Biodegrad."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1620\/tjem.2024.J122","article-title":"Vitamin D Supplementation Reduces Functional Impairment of Hippocampus Caused by Dexamethasone","volume":"266","author":"Su","year":"2025","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"106262","DOI":"10.1016\/j.eplepsyres.2019.106262","article-title":"The effect of vitamin D3 and paricalcitol on penicillin-induced epileptiform activity in rats","volume":"159","author":"Sumbul","year":"2020","journal-title":"Epilepsy Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1210\/jc.2010-0502","article-title":"Effect of a single oral dose of 600,000 IU of cholecalciferol on serum calciotropic hormones in young subjects with vitamin D deficiency: A prospective intervention study","volume":"95","author":"Cipriani","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pepe, J., Colangelo, L., Pilotto, R., De Martino, V., Ferrara, C., Scillitani, A., Cilli, M., Minisola, S., Singh, R., and Cipriani, C. (2024). Short-Term Effects of Escalating Doses of Cholecalciferol on FGF23 and 24,25(OH)2 Vitamin D Levels: A Preliminary Investigation. Nutrients, 16.","DOI":"10.3390\/nu16213600"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/s42003-020-01440-z","article-title":"Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI","volume":"3","author":"Timm","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Xu, Y., Liu, Z., Sun, J., Pan, Q., Sun, F., Yan, Z., and Hu, X. (2011). Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028335"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14633","DOI":"10.1039\/C8RA00975A","article-title":"Thymoquinone protects against cardiac damage from doxorubicin-induced heart failure in Sprague-Dawley rats","volume":"8","author":"Pei","year":"2018","journal-title":"RSC Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e13400","DOI":"10.1111\/apha.13400","article-title":"Doxorubicin-induced skeletal muscle atrophy: Elucidating the underlying molecular pathways","volume":"229","author":"Hiensch","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_63","first-page":"101","article-title":"Delayed doxorubicin cardiomyopathy in the rat: Possible role of reduced food intake","volume":"5","author":"Canepari","year":"1994","journal-title":"Cardioscience"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Law, M.L. (2022). Cancer cachexia: Pathophysiology and association with cancer-related pain. Front. Pain Res., 3.","DOI":"10.3389\/fpain.2022.971295"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Cella, P.S., Matos, R.L.N., Marinello, P.C., Costa, J.C.D., Moura, F.A., Bracarense, A.P.F.R.L., Chimin, P., and Deminice, R. (2024). Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0301379"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00421-019-04104-x","article-title":"Mechanisms of vitamin D on skeletal muscle function: Oxidative stress, energy metabolism and anabolic state","volume":"119","author":"Dzik","year":"2019","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/s42003-022-04246-3","article-title":"Vitamin D status modulates mitochondrial oxidative capacities in skeletal muscle: Role in sarcopenia","volume":"5","author":"Salles","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/jcsm.12059","article-title":"Pathophysiology of anorexia in the cancer cachexia syndrome","volume":"6","author":"Ezeoke","year":"2015","journal-title":"J. Cachexia Sarcopenia Muscle."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Romeu Montenegro, K., Amarante Pufal, M., and Newsholme, P. (2021). Vitamin D Supplementation and Impact on Skeletal Muscle Function in Cell and Animal Models and an Aging Population: What Do We Know So Far?. Nutrients, 13.","DOI":"10.3390\/nu13041110"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.cell.2013.03.028","article-title":"A vitamin D receptor\/SMAD genomic circuit gates hepatic fibrotic response","volume":"153","author":"Ding","year":"2013","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ajpath.2023.11.016","article-title":"Vitamin D Receptor Activation Reduces Hepatic Inflammation via Enhancing Macrophage Autophagy in Cholestatic Mice","volume":"194","author":"Wen","year":"2024","journal-title":"Am. J. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"117599","DOI":"10.1016\/j.lfs.2020.117599","article-title":"New molecular and biochemical insights of doxorubicin-induced hepatotoxicity","volume":"250","author":"Prasanna","year":"2020","journal-title":"Life Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3892\/etm.2011.205","article-title":"Prevalence of serum vitamin D deficiency and insufficiency in cancer: Review of the epidemiological literature","volume":"2","author":"Gupta","year":"2011","journal-title":"Exp. Ther. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00384-008-0593-y","article-title":"Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer","volume":"24","author":"Fakih","year":"2009","journal-title":"Int. J. Color. Dis."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/7\/1097\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T10:08:54Z","timestamp":1774865334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/7\/1097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,29]]},"references-count":74,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["nu18071097"],"URL":"https:\/\/doi.org\/10.3390\/nu18071097","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,29]]}}}