{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:32:42Z","timestamp":1774945962721,"version":"3.50.1"},"reference-count":61,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"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":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nephrotoxicity is a prominent complication of methotrexate (MTX) therapy that limits clinicians in its extensive use. MTX triggers oxidative burden and inflammation, so the nephroprotective potential of the synthetic derivative of 1,3,4\u2010oxadiazole (5b) was explored in this research. Male Wistar rats were divided into four groups i.e., control group, MTX group, 5b (5\u2009mg\/kg)\u2009+\u2009MTX group and 5b (10\u2009mg\/kg)\u2009+\u2009MTX group, respectively. All treatments were given, intraperitoneally (\n                    <jats:italic>i.p<\/jats:italic>\n                    .) during 12 days of the animal model. The MTX\u2010induced nephrotoxicity was evaluated by renal function markers i.e., serum creatinine (Cret), blood urea nitrogen (BUN), and albumin (Alb). Furthermore, antioxidant markers, catalase (CAT), glutathione\u2010S\u2010transferase (GST), and reduced glutathione (GSH), and oxidative stress, markers lipid peroxidase (LPO) and nitric oxide (NO), were analyzed. Pro\u2010inflammatory cytokines, interleukin\u20101\u03b2 (IL\u20101\u03b2) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), were also calculated. DNA damage was assessed by the comet assay. Histopathological staining (Hematoxylin and eosin, Masson's trichrome) was done and immunohistochemistry was performed against Caspase\u20103, Nrf2, HO\u20101, TLR\u20104, TNF\u2010\u03b1, and NF\u2010\u03baB. A significant improvement in the serum Cret, BUN, and Alb was observed in (5b) treated groups. Antioxidant markers were elevated, oxidative stress markers and pro\u2010inflammatory cytokines were reduced, moreover, histopathological analysis revealed less tissue damage in (5b) administered groups. Immunohistochemistry showed increased immune expression of Nrf2 and HO\u20101 and decreased expression of TLR\u20104, TNF\u2010\u03b1, Caspase\u20103, and NF\u2010\u03baB in 5b (5\u2009mg\/kg)\u2009+\u2009MTX group and 5b (10\u2009mg\/kg)\u2009+\u2009MTX group as compared to the MTX group. Hence, the results of this study favor the use of (5b) against MTX\u2010induced nephrotoxicity.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70084","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T13:22:55Z","timestamp":1733923375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nephroprotective Potential of 1,3,4\u2010Oxadiazole Derivative Against Methotrexate\u2010Induced Nephrotoxicity in Rats by Upregulating Nrf2 and Downregulating NF\u2010\u03baB and TNF\u2010\u03b1 Signaling Pathways"],"prefix":"10.1002","volume":"38","author":[{"given":"Zubaria","family":"Rafique","sequence":"first","affiliation":[{"name":"Department of Pharmacy,Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Aabid","sequence":"additional","affiliation":[{"name":"Department of Pharmacy,Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Humaira","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences Riphah International University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayema","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy,Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jehan zeb","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy,Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Waqas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy,Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0638-2271","authenticated-orcid":false,"given":"Nadeem","family":"Irshad","sequence":"additional","affiliation":[{"name":"Department of Pharmacy,Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxres\/tfae119"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11290821"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016080867"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.21608\/besps.2023.226616.1150"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxics11050398"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2020.1811307"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.10.088"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-020-04547-y"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.24482"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.03.041"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e03683"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/572013"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm2013248"},{"issue":"3","key":"e_1_2_9_15_1","first-page":"9","article-title":"1, 3, 4\u2010Oxadiazole: a Potent Drug Candidate With Various Pharmacological Activities","volume":"3","author":"Nagaraj C. 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