{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T17:35:18Z","timestamp":1775756118483,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug\u2010induced organ toxicity is a frequently encountered obstacle in the field of medical practice that limits the use of numerous pharmacologically valuable drugs. Methotrexate (MTX)\u2010induced organ toxicity is unfortunately the rate\u2010limiting factor for its clinical application. In the current study, MTX injection induced significant renal and hepatic toxicities manifested on functional, biochemical, and histopathological scales. This was associated with a significant elevation in both renal and hepatic contents of TNF\u2010related apoptosis\u2013inducing ligand (TRAIL) and caspase\u20108, biomarkers of tissue apoptosis. Inline, immunohistochemical analysis confirmed that tissue increased expression of Ki67 as a biomarker of tissue regeneration in both organs. Tranilast (TRAN) is a small molecular weight anti\u2010inflammatory and antiallergic agent. TRAN's coadministration with MTX in the current study induced a significant tissue recovery via modulation of TRAIL\/caspase\u20108 signaling and modulation of apoptosis\u2010induced tissue proliferation confirmed by quantification of Ki67 expression. In conclusion, TRAN can be proposed as an effective drug to attenuate MTX\u2010induced organ toxicity via modulation of apoptosis\u2010induced tissue proliferation pathway.<\/jats:p>","DOI":"10.1002\/jbt.22466","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T14:25:53Z","timestamp":1581431153000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tranilast attenuates methotrexate\u2010induced renal and hepatic toxicities: Role of apoptosis\u2010induced tissue proliferation"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5974-2899","authenticated-orcid":false,"given":"Manar Gamal","family":"Helal","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Mansoura University  Mansoura Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5529-6994","authenticated-orcid":false,"given":"Eman","family":"Said","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Mansoura University  Mansoura Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.10.113"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.11-6-694"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200124010-00003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-0844(199712)15:4<259::AID-CBF749>3.0.CO;2-D"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.5414\/CNP64315"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1676"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199804093381507"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8FO00131F"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.120"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-013-0949-x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.01.022"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.47"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2014.10.009"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4161"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-011-0117-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2015.06.019"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2015-0070"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2013.07.005"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3281670"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2307\/3575520"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5691"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.82"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.12.064"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.216"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2017.04.009"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174295"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.03.041"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327116637414"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08119"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.01.058"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260307"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215540305101212"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087273"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1413-8"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124612"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1117634"},{"key":"e_1_2_7_38_1","first-page":"1061","volume":"295","author":"Capper E. 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