{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:49:33Z","timestamp":1787017773718,"version":"build-2736575974"},"reference-count":77,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":109,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006261","name":"Taif University","doi-asserted-by":"publisher","award":["TURSP-2020\/38"],"award-info":[{"award-number":["TURSP-2020\/38"]}],"id":[{"id":"10.13039\/501100006261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>\n                    Drug\u2010induced liver injury (DILI) is the main cause of liver damage mediated by the excretion of toxic active drug metabolites. Omega\u20103 fatty acids and vitamin C have potent antioxidant, anti\u2010inflammatory, and antiapoptotic effects that could offer protection against oxidative stress and liver damage. This study evaluated the hepatoprotective effect of omega\u20103 and vitamin C alone as well as in a combined form in methotrexate\u2010 (MTX\u2010) induced acute liver injury in mice. Male ICR mice of seven groups (7 mice per group) were used. Groups 1 (control group) and 2 (MTX) received 0.9% saline\/day (po) for 9 days. Groups 3 and 4 received 100 and 200\u2009mg\/kg bw\/day omega\u20103 (po), respectively, for 9 days. Groups 5 and 6 received 100 and 200\u2009mg\/kg bw\/day vitamin C (po), respectively, for 9 days, while group 7 received omega\u20103 (100\u2009mg\/kg bw\/day) and vitamin C (100\u2009mg\/kg bw\/day) (po) for 9 days. All animals in groups 2 to 7 received 20\u2009mg\/kg\/day MTX (I.P.) once on the 10\n                    <jats:sup>th<\/jats:sup>\n                    day. Our results revealed that MTX significantly induced the elevation of transaminases, alkaline phosphates (ALP), lactate dehydrogenase (LDH), and malonaldehyde (MDA) while depleting the levels of superoxide dismutase (SOD) and glutathione (GSH) when compared to the control group. Treatment with omega\u20103 fatty acids or vitamin C significantly attenuated the antioxidants and biochemical alterations in a dose\u2010independent manner. Our molecular docking study of ligand\u2010receptor interaction revealed that both ascorbic acid and omega\u20103 docked well to the binding cavity of LDH with high binding affinities of \u20135.20 and \u20134.50\u2009kcal\/mol, respectively. The histopathological features were also improved by treatment with omega\u20103 and vitamin C. The combined form of omega\u20103 and vitamin C showed a remarkable improvement in the liver enzymes, oxidative stress biomarkers, and the histopathological architecture of the mice. Conclusively, the combination of omega\u20103 and vitamin C demonstrated a synergistic therapeutic effect against MTX\u2010intoxicated mice, hence representing a potential novel strategy for the management of drug\u2010induced liver disorders.\n                  <\/jats:p>","DOI":"10.1155\/2022\/4122166","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T18:05:09Z","timestamp":1650477909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Combination Treatment of Omega\u20103 Fatty Acids and Vitamin C Exhibited Promising Therapeutic Effect against Oxidative Impairment of the Liver in Methotrexate\u2010Intoxicated Mice"],"prefix":"10.1155","volume":"2022","author":[{"given":"Mohammed","family":"Alorabi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doha 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