{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:47:03Z","timestamp":1790880423466,"version":"4.1.0"},"reference-count":48,"publisher":"SAGE Publications","issue":"12_suppl","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100005001","name":"Ahvaz Jundishapur University of Medical Sciences","doi-asserted-by":"publisher","award":["TRC-9802"],"award-info":[{"award-number":["TRC-9802"]}],"id":[{"id":"10.13039\/501100005001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Due to the fact that methotrexate is widely used both as an immunosuppressive drug and as a chemotherapy agent, many studies are needed to reduce the side effects of this drug on non-target organs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study was designed to investigate the effects of epicatechin (Epi) on MTX (methotrexate)-induced hepatotoxicity in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research Design<\/jats:title>\n                    <jats:p>After 1 week for adaptation, we randomly divided 42 male Naval Medical Research Institute mice into six groups: (I) control; (II) Epi (100 mg\/kg, po); (III) MTX (20 mg\/kg, i.p.) on the fifth day; and (IV, V, and VI) Epi (25, 50, and 100 mg\/kg, po) + MTX (20 mg\/kg, i.p.) on the fifth day. At day 10, the mice were sacrificed and serum factors, oxidative stress markers, and inflammatory cytokines were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MTX increased activity level of serum enzymes (alanine aminotransferase and aspartate aminotransferase), lipid peroxidation marker (malondialdehyde), and inflammatory factors including interleukin-1 beta, tumor necrosis factor-alpha, and nitric oxide. Furthermore, MTX decreased glutathione level and activity level of catalase, superoxide dismutase, and glutathione peroxidase. Epi was able to reduce the destructive effects of oxidative\/antioxidant system imbalance and inflammatory reactions and also histopathological damage in MTX intoxicated mice. Epi pretreatment reduced liver dysfunction by improving the antioxidant defense system, anti-inflammatory effects, and alleviation of histopathological damage in MTX hepatotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Accordingly, Epi can be used as a therapeutic agent in hepatotoxicity associated with MTX chemotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271211047924","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T03:51:16Z","timestamp":1637553076000},"page":"S603-S610","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":30,"title":["Epicatechin ameliorative effects on methotrexate-induced hepatotoxicity in 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