{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T11:00:04Z","timestamp":1768647604793,"version":"3.49.0"},"reference-count":44,"publisher":"Georg Thieme Verlag KG","issue":"01","funder":[{"DOI":"10.13039\/501100003970","name":"Isfahan University of Medical\n                        Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003970","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cyclophosphamide is known to cause liver dysfunction. This study investigated the\n                    protective role of vitamin D supplementation against cyclophosphamide -induced\n                    liver dysfunction in adult male rats. The rats receiving cyclophosphamide were\n                    treated with vitamin D at doses of 1,000 and 3,000 IU\/kg. At the end of the\n                    study period, biochemical and histopathological evaluations were conducted after\n                    the animals were sacrificed. The levels of aspartate aminotransferase, alanine\n                    aminotransferase, alkaline phosphatase, lactate dehydrogenase, nitric oxide, and\n                    bilirubin were significantly elevated in the cyclophosphamide group compared to\n                    the control group (p&lt;0.001). Conversely, these levels were\n                    significantly decreased in the vitamin D treatment groups (p&lt;0.01).\n                    Additionally, the activities of the catalase and glutathione peroxidase were\n                    significantly lower in the cyclophosphamide group than in controls\n                    (p&lt;0.01), while they increased significantly in the vitamin D groups\n                        (p&lt;0.001). According to a semi-quantitative scoring system, the\n                    highest scores for pathological lesions were observed in the cyclophosphamide\n                    group, with lower scores in the vitamin D groups. The differences between the\n                    cyclophosphamide group and both treated groups were statistically significant\n                        (p&lt;0.05). These results indicate that vitamin D, through its\n                    antioxidant properties, positively influenced liver enzyme levels altered by\n                    cyclophosphamide.<\/jats:p>","DOI":"10.1055\/a-2734-1920","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:16:21Z","timestamp":1764116181000},"page":"20-27","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Protective Role of Vitamin D Supplementation on\n                    Cyclophosphamide-Induced Liver Enzyme Alterations in Adult Male\n                    Rats"],"prefix":"10.1055","volume":"76","author":[{"given":"Tania","family":"Nazem","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Isfahan\n                    Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences,\n                    Isfahan, Iran (the Islamic Republic of)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Hosseini-Sharifabad","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of\n                    Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences,\n                    Isfahan, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Reza","family":"Mofid","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Isfahan\n                    Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences,\n                    Isfahan, Iran (the Islamic Republic of)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Hashemnia","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Faculty of Veterinary\n                    Medicine, Razi University, Kermanshah, Iran (the Islamic Republic\n                    of)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Habib-Allah","family":"Nazem","sequence":"additional","affiliation":[{"name":"Payame Noor University, Isfahan, Iran (the Islamic\n                    Republic of)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-9439","authenticated-orcid":false,"given":"Adel","family":"Mohammadalipour","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Isfahan\n                    Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences,\n                    Isfahan, Iran (the Islamic Republic of)"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.3389\/fphar.2018.01300","article-title":"Evolution of cancer pharmacological treatments at the turn of the third\n             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hepatotoxicity,\n                    molecular mechanisms, and histopathological characteristics","volume":"11","author":"A M Jali","year":"2023","journal-title":"Biomedicines"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.freeradbiomed.2017.05.006","article-title":"Cyclophosphamide and acrolein induced oxidative stress leading to deterioration\n                    of metaphase II mouse oocyte quality","volume":"110","author":"R Jeelani","year":"2017","journal-title":"Free Radic Biol Med"},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1080\/01480545.2020.1810262","article-title":"Escin attenuates oxidative damage, apoptosis and lipid peroxidation in a model\n                    of cyclophosphamide-induced liver damage","volume":"45","author":"M Cengiz","year":"2022","journal-title":"Drug Chem Toxicol"},{"issue":"07","key":"ref7","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1055\/a-1842-7596","article-title":"Dipeptidyl peptidase-4 inhibitor sitagliptin exhibits antioxidant mechanism for\n                    abrogation of cyclophosphamide-induced cardiac damage and oxidative hepatorenal\n                    toxicity in rats","volume":"72","author":"A C Famurewa","year":"2022","journal-title":"Drug Res (Stuttg)"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s13568-020-01064-w","article-title":"Synthesis of cyclophosphamide metabolites by a peroxygenase from Marasmius\n                    rotula for toxicological studies on human cancer cells","volume":"10","author":"S Steinbrecht","year":"2020","journal-title":"AMB Express"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"17536","DOI":"10.1038\/srep17536","article-title":"Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing\n                    disordered homeostasis of glutathione and bile acid","volume":"5","author":"H Zhu","year":"2015","journal-title":"Sci Rep"},{"issue":"05","key":"ref10","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1016\/j.sjbs.2021.03.039","article-title":"Lucrative antioxidant effect of metformin against cyclophosphamide induced\n                    nephrotoxicity","volume":"28","author":"A F Tohamy","year":"2021","journal-title":"Saudi J Biol Sci"},{"issue":"11","key":"ref11","doi-asserted-by":"crossref","first-page":"e0165667","DOI":"10.1371\/journal.pone.0165667","article-title":"Protective effects of essential oils as natural antioxidants against\n                    hepatotoxicity induced by cyclophosphamide in mice","volume":"11","author":"S A Sheweita","year":"2016","journal-title":"PLoS One"},{"issue":"03","key":"ref12","doi-asserted-by":"crossref","first-page":"e0174295","DOI":"10.1371\/journal.pone.0174295","article-title":"Hepatoprotective effect of sitagliptin against 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Sherif","year":"2018","journal-title":"Int Immunopharmacol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.semcancer.2020.05.018","article-title":"An update on vitamin D signaling and cancer","volume":"79","author":"C Carlberg","year":"2022","journal-title":"Semin Cancer Biol"},{"issue":"04","key":"ref17","doi-asserted-by":"crossref","first-page":"948","DOI":"10.3390\/antiox12040948","article-title":"Vitamin D determinants, status, and antioxidant\/anti-inflammatory-related\n                    effects in cardiovascular risk and disease: not the last word in the\n                    controversy","volume":"12","author":"G Della Nera","year":"2023","journal-title":"Antioxidants (Basel)"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/oby.21757","article-title":"1,25(OH)2D3 attenuates hepatic steatosis by inducing\n                    autophagy in mice","volume":"25","author":"R 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cyclophosphamide-induced cardiotoxicity","volume":"42","author":"M M Mahmoud Refaie","year":"2023","journal-title":"Hum Exp Toxicol"},{"issue":"06","key":"ref28","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1002\/ptr.6951","article-title":"Protection by ginseng saponins against cyclophosphamide-induced liver injuries\n                    in rats by induction of cytochrome P450 expression and mediation of the\n                    l-arginine\/nitric oxide pathway based on metabolomics","volume":"35","author":"J Chen","year":"2021","journal-title":"Phytother Res"},{"issue":"02","key":"ref29","doi-asserted-by":"crossref","first-page":"424","DOI":"10.3390\/biomedicines11020424","article-title":"Vitamin D ameliorates the hepatic oxidative damage and fibrotic effect caused by\n                    thioacetamide in rats","volume":"11","author":"A Megahed","year":"2023","journal-title":"Biomedicines"},{"key":"ref30","first-page":"319","article-title":"Antioxidative effect of vitamin D3 on zinc-induced oxidative stress in CNS","volume":"1053","author":"A M Lin","year":"2005","journal-title":"Ann N Y Acad Sci"},{"issue":"03","key":"ref31","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3390\/nu15030769","article-title":"Effects of vitamin D on cardiovascular risk and oxidative stress","volume":"15","author":"G Renke","year":"2023","journal-title":"Nutrients"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.phrs.2018.11.011","article-title":"The effect of vitamin D supplementation on oxidative stress parameters: A\n                    systematic review and meta-analysis of clinical trials","volume":"139","author":"M Sepidarkish","year":"2019","journal-title":"Pharmacol Res"},{"issue":"01","key":"ref33","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3892\/etm.2024.12565","article-title":"Therapeutic potential of vitamin D3 in mitigating high glucose\u2011induced renal\n                    damage: Mechanistic insights into oxidative stress inhibition and TXNIP\/NLRP3\n                    signaling pathway blockade","volume":"28","author":"G Li","year":"2024","journal-title":"Exp Ther Med"},{"issue":"02","key":"ref34","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000346808","article-title":"Anti-oxidative effect of vitamin D analog on incipient vascular lesion in\n                    non-obese type 2 diabetic rats","volume":"37","author":"K Kono","year":"2013","journal-title":"Am J Nephrol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jsbmb.2014.12.012","article-title":"NO-dependent proliferation and migration induced by Vitamin D in HUVEC","volume":"149","author":"P Pittarella","year":"2015","journal-title":"J Steroid Biochem Mol Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"117263","DOI":"10.1016\/j.ejmech.2025.117263","article-title":"A comparative study on the antioxidant and antiglycation properties of different\n                    vitamin D forms","volume":"285","author":"C Pawlukianiec","year":"2025","journal-title":"Eur J Med Chem"},{"issue":"02","key":"ref37","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1017\/S0954422419000064","article-title":"Mechanisms of vitamin D action in skeletal muscle","volume":"32","author":"K R Montenegro","year":"2019","journal-title":"Nutr Res Rev"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"75","DOI":"10.15407\/ubj87.03.075","article-title":"Vitamin D(3) contribution to the regulation of oxidative metabolism in the liver\n                    of diabetic mice","volume":"87","author":"D Labudzynskyi","year":"2015","journal-title":"Ukr Biochem J"},{"issue":"19","key":"ref39","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\n                    patients with chronic liver disease: A protocol for a systematic review and\n                    meta-analysis","volume":"99","author":"T Chen","year":"2020","journal-title":"Medicine (Baltimore)"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jss.2019.05.020","article-title":"Potential effect of 1,25 dihydroxyvitamin D(3) on thioacetamide-induced\n                    hepatotoxicity in rats","volume":"243","author":"Z N \u00d6zdemir-Kumral","year":"2019","journal-title":"J Surg Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4103\/2008-7802.177898","article-title":"Cyclophosphamide-induced hepatotoxicity in wistar rats: the modulatory role of\n                    gallic acid as a hepatoprotective and chemopreventive phytochemical","volume":"7","author":"A A Oyagbemi","year":"2016","journal-title":"Int J Prev Med"},{"issue":"09","key":"ref42","doi-asserted-by":"crossref","first-page":"e04842","DOI":"10.1016\/j.heliyon.2020.e04842","article-title":"Dietary vitamin D 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