{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T23:54:14Z","timestamp":1792367654796,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Methotrexate (MTX) is a medication that is frequently prescribed for the treatment of both malignant disorders and inflammatory pathologies. However, its use is limited by dose\u2010dependent pulmonary toxicity. The present study investigated the protective effects of silymarin (SLM) against MTX\u2010induced lung injury by evaluating apoptosis, oxidative stress, autophagy, inflammation and histopathological changes in rats. Twenty\u2010eight Wistar albino rats were assigned to the Control, SLM (50\u2009mg\/kg, p. o.), MTX (20\u2009mg\/kg, i. p.), and MTX\u2009+\u2009SLM groups. MTX treatment led to a significant elevation in malondialdehyde levels along with marked reductions in glutathione content and antioxidant enzyme activities, concomitant with decreased Nrf2 and HO\u20101 expression, indicating pronounced oxidative stress (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Additionally, MTX has been shown to raise Bax and Caspase\u20103 and diminish Bcl\u20102 while simultaneously inducing NF\u2010\u03baB, TNF\u2010\u03b1, TLR\u20104, and HMGB1. This confirms the presence of increased inflammation and mitochondrial\u2010dependent apoptosis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Furthermore, MTX elevated the expression of LC3A, LC3B, and Beclin\u20101, suggesting an increase in autophagy (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). SLM supplementation greatly improved antioxidant status, increased Nrf2\/HO\u20101, decreased inflammatory signaling, modulated Caspase\u20103\/Bax\/Bcl\u20102 expression, and suppressed MTX\u2010induced autophagy (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). These biochemical findings were subsequently corroborated by histopathological analysis. In summary, the present study demonstrates that SLM offers a promising protective effect against MTX\u2010induced pulmonary damage, operating through mechanisms involving antioxidant, anti\u2010autophagic, anti\u2010inflammatory and anti\u2010apoptotic actions. These results underscore the potential of SLM as a complementary therapeutic agent in mitigating lung toxicity induced by chemotherapy agents.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70829","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T03:27:47Z","timestamp":1775532467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ameliorative Role of Silymarin in Methotrexate\u2010Induced Pulmonary Damage: A Multi\u2010Pathway Molecular Approach"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5367-0743","authenticated-orcid":false,"given":"Aydin","family":"Genc","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Veterinary Medicine Bingol University Bingol T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emre","family":"Sahin","sequence":"additional","affiliation":[{"name":"Animal Nutrition and Nutritional Disease Department, Faculty of Veterinary Medicine Bingol University Bingol T\u00fcrkiye"},{"name":"Department of Veterinary Biostatistics, Health Sciences Institute Ankara University Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eren","family":"Cankaya","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine Firat University Elazig Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.17758"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11110582"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-020-04773-4"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2020.1736209"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox4010204"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16040520"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2017.2935"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(66)90167-9"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/34.3.497"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0076-6879(84)05016-3"},{"key":"e_1_2_11_12_1","first-page":"248","article-title":"Determination of Enzyme Activity in Lipid Peroxidation and Glutathione Pathways","volume":"15","author":"Matkovics B.","year":"1988","journal-title":"Laboratoriumi Diagnosztika"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(68)90092-4"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_11_16_1","first-page":"12","volume-title":"Manual of Histologic Staining Methods of the Armed Forces Institute of Pathology","author":"Luna L. 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