{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:58:20Z","timestamp":1790377100826,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Methotrexate (MTX) is a chemotherapeutic agent used for treating several types of cancer as well as psoriasis and rheumatoid arthritis, but its use is limited due to its nephrotoxicity. The purpose of this research work was to observe ameliorative effects of L\u2010carnitine (LC) toward renal toxicity caused by MTX and mechanisms responsible for these effects. Thirty\u2010two male Sprague\u2010Dawley rats were divided into four groups (eight rats\/group), control group (received saline), MTX group (20\u2009mg\/kg\/i.p. once), LC group (500\u2009mg\/kg\/i.p. for 5\u00a0days), and MTX\u2009+\u2009LC group (received a single MTX dose 20\u2009mg\/kg\/i.p. followed by LC 500\u2009mg\/kg\/i.p. for 5\u00a0days). Histopathological examinations, lipid oxidation marker, malondialdehyde (MDA), and the antioxidant superoxide dismutase (SOD) as well as inflammatory (tumor necrosis factor\u2010\u03b1 [TNF\u2010\u03b1] and interleukin\u20106 [IL\u20106]) and apoptotic markers (Bax, Bcl2, and caspase\u20103) were used to assess renal toxicity. Moreover, the protein levels of silent information regulator 1 (SIRT1) and its downstream signaling targets, peroxisome proliferator\u2010activated receptor\u2010\u03b3 coactivator\u20101\u03b1 (PGC\u20101\u03b1), and nuclear factor erythroid 2\u2010related factor 2 (Nrf2) in addition to heme oxygenase\u20101 (HO\u20101) were measured. LC significantly protected against MTX\u2010induced nephrotoxicity. It ameliorated MTX\u2010induced renal histopathological changes and diminished MTX\u2010induced renal oxidative stress, renal inflammation, and apoptosis. LC also upregulated the expression of SIRT1 and PGC\u20101 as well as Nrf2 and HO\u20101. By controlling the expression of renal SIRT1\/PGC\u20101\/Nrf2\/HO\u20101, LC displayed antioxidant, anti\u2010inflammatory, and anti\u2010apoptotic activities. Hence, using LC supplements may help prevent negative MTX side effects.<\/jats:p>","DOI":"10.1002\/jat.4503","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T03:08:03Z","timestamp":1686712083000},"page":"1667-1675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["L\u2010carnitine reverses methotrexate\u2010induced nephrotoxicity in experimental rat model: Insight on SIRT1\/PGC\u20101\u03b1\/Nrf2\/HO\u20101 axis"],"prefix":"10.1002","volume":"43","author":[{"given":"Sara M.","family":"Radwan","sequence":"first","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Alqulaly","sequence":"additional","affiliation":[{"name":"Physiology Department, Damietta Faculty of Medicine Al\u2010Azhar University  Damietta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdy Y.","family":"Elsaeed","sequence":"additional","affiliation":[{"name":"Physiology Department, Damietta Faculty of Medicine Al\u2010Azhar University  Damietta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimaa Z.","family":"Elshora","sequence":"additional","affiliation":[{"name":"Histology Department, Faculty of Medicine for Girls Al\u2010Azhar University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa H.","family":"Atwa","sequence":"additional","affiliation":[{"name":"Forensic medicine and clinical toxicology Department, Faculty of Medicine Al\u2010Azhar University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7711-0473","authenticated-orcid":false,"given":"Eman F.","family":"Wasfey","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/0886022X.2016.1216722"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8100430"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14081620"},{"issue":"6","key":"e_1_2_7_5_1","first-page":"2191","article-title":"Capsaicin ameliorate the nephrotoxicity induced by methotrexate","volume":"34","author":"Aldossary S. 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