{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:55:38Z","timestamp":1753869338875,"version":"3.41.2"},"reference-count":78,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"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":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cisplatin is a chemotherapeutic agent whose therapeutic use is greatly limited by the associated organs' toxicity and particularly, testicular toxicity. Cisplatin\u2010induced testicular damage reported being mediated through mitochondria\u2010mediated apoptosis, inflammation, and oxidative stress. Evidence showed that tranilast (TRN) has the ability to restore the oxidative status and modulate TRAIL\/caspase\u20108 signaling. This led us to hypothesize that TRN could abrogate cisplatin\u2010induced testicular and epididymal injuries via inhibiting oxidative stress and modulating proliferation and TRAIL\/caspase\u20108\/cJNK signaling. Cisplatin injection induced oligospermia and abnormalities in testicular and epididymal structure along with impaired oxidative status. TRN administration (100 or 300\u2009mg\/kg) for 7 days post\u2010cisplatin injection preserved spermatogenesis and restored testicular and epididymal architecture, but restoration was more so in TRN300 than TRN100. This was in line with the restoration of balanced oxidative status as indicated by the increased total antioxidant capacity, glutathione and superoxide dismutase activity, and the decreased malondialdehyde content in testes (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 vs. cisplatin). TRN increased the cell proliferation revealed by the increased expression of proliferating cell nuclear antigen in a dose\u2010dependent manner (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 vs. cisplatin) whereas only TRN300 decreased testicular cJNK, TRAIL, and caspase\u20108 expression (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 vs. cisplatin). Moreover, TRN dose\u2010dependently inhibited the pro\u2010inflammatory transcription factor NF\u2010<jats:sc>k<\/jats:sc>B and the cytokine TNF\u2010\u03b1 expressions in testes. In conclusion, TRN300 was more effective than TRN100 in alleviating cisplatin\u2010induced testicular and epididymal injuries and in enhancing spermatogenesis. This curative effect of TRN might be mediated through its antioxidant and anti\u2010inflammatory impacts along with its modulatory impact on cJNK\/TRAIL\/caspase\u20108 signaling favoring proliferation rather than apoptosis.<\/jats:p>","DOI":"10.1002\/jbt.22817","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T11:34:58Z","timestamp":1622201698000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tranilast abrogates cisplatin\u2010induced testicular and epididymal injuries: An insight into its modulatory impact on apoptosis\/proliferation"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-6324","authenticated-orcid":false,"given":"Mirhan N.","family":"Makled","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":[[2021,5,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.5487\/TR.2017.33.3.255"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8487248"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-015-0274-1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-016-0833-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2016.02.002"},{"key":"e_1_2_7_7_1","first-page":"64","volume":"2","author":"Tousson E.","year":"2014","journal-title":"J. Cancer Res. Treat."},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.074134"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/19396368.2018.1541114"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.992302"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5453.664"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.301"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4161"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2015-0070"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22466"},{"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","first-page":"7356","volume":"17","author":"Yin D. D.","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2015.06.019"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1254\/fpj.99.241"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20975"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2020.12.008"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deg199"},{"key":"e_1_2_7_23_1","first-page":"2","volume":"1","author":"Johnsen S. G.","year":"1970","journal-title":"Hormones"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1986.tb00862.x"},{"issue":"8","key":"e_1_2_7_25_1","first-page":"1","volume":"9","author":"Wang T. E.","year":"2020","journal-title":"Antioxidants"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1974.tb03714.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8100465"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.13227"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.43.4.244"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-500X.119726"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2011.26"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.20693"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.04.059"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mefs.2010.07.001"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jomh.2011.08.083"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/362049"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12894-018-0421-9"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dep058"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21593"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.07.025"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2012.08.012"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2016.02.017"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S120014"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.4161\/oxim.1.1.6843"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1179\/135100008X259169"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bionut.2012.08.005"},{"key":"e_1_2_7_49_1","first-page":"184","volume":"4","author":"Cayir K.","year":"2009","journal-title":"Cent. Eur. J. Med."},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.5301\/RU.2012.9032"},{"key":"e_1_2_7_51_1","doi-asserted-by":"crossref","first-page":"e02247","DOI":"10.1016\/j.heliyon.2019.e02247","volume":"5","author":"Yadav Y. C.","year":"2019","journal-title":"Heliyon"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.12197"},{"key":"e_1_2_7_53_1","first-page":"9","volume":"2","author":"Ramadan R.","year":"2017","journal-title":"J. Appl. Vet. Sci."},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq355"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118984"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.12247"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.12332"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.12593"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2020.103334"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01215-8"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.49.33091"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008656"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.01.022"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e15-04-0209"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.178"},{"key":"e_1_2_7_66_1","first-page":"4227","volume":"9","author":"Dang Y.","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.13786"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2017.1322618"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12606"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.4.856"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2005.05.003"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2008.12.001"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.06.019"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1080\/10520295.2017.1401661"},{"key":"e_1_2_7_75_1","first-page":"176","volume":"42","author":"Nakashima T.","year":"2019","journal-title":"Oncol. Rep."},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030608"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124612"},{"key":"e_1_2_7_78_1","first-page":"162","volume":"29","author":"Lee W. J.","year":"2002","journal-title":"J. Korean Soc. Plast. Reconstr. Surg."},{"key":"e_1_2_7_79_1","first-page":"2471","volume":"32","author":"Rogosnitzky M.","year":"2012","journal-title":"Anticancer Res."}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22817","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.22817","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T21:02:12Z","timestamp":1693342932000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.22817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,28]]},"references-count":78,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/jbt.22817"],"URL":"https:\/\/doi.org\/10.1002\/jbt.22817","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"type":"print","value":"1095-6670"},{"type":"electronic","value":"1099-0461"}],"subject":[],"published":{"date-parts":[[2021,5,28]]},"assertion":[{"value":"2020-12-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22817"}}