{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:15:07Z","timestamp":1790036107940,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"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":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As a serotonin antagonist, tropisetron positively affects blood glucose lowering, insulin synthesis, pancreas inflammation, and apoptosis in diabetes. Reproductive disorders are one of the diabetes\u2010induced chronic complications. The present study aimed to evaluate the effect of tropisetron on diabetes\u2010induced testicular inflammation, its signaling pathway, and mir146a. To this end, animals were assigned to the control, tropisetron, diabetes (DM), DM\u2010tropisetron, and DM\u2010glibenclamide groups. Streptozotocin (50\u2009mg\/kg) was intraperitoneally injected to provide diabetes. Tropisetron and glibenclamide were then administrated intraperitoneally for 2 weeks after diabetes induction. Testes histology, real\u2010time polymerase chain reaction, western blot analysis, ELISA, and immunohistochemistry assays were also performed. The finding revealed that tropisetron significantly improved diabetes\u2010induced testis damages, lowered TLR4, TRAF6, IRAK1, NF\u2010\u03baB, and caspase3 protein expressions, and decreased TNF\u2010\u03b1 and IL\u20101 levels. Moreover, the mir146a expression declined following the tropisetron treatment. This study demonstrated that the significant role of tropisetron in lowering testicular inflammation and apoptosis might have been due to the inhibition of the TLR4\/IRAK1\/TRAF6 signaling pathway and thereby the attenuation of NF\u2010\u03baB and caspase3 expression and inflammatory cytokines. Furthermore, the downregulation of mir146a, as an inflammatory microRNA interacting with TLR4, showed another pathway, through which tropisetron improved diabetes\u2010induced testicular injuries.<\/jats:p>","DOI":"10.1002\/jbt.23272","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T10:30:42Z","timestamp":1670841042000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Tropisetron improved testicular inflammation in the streptozotocin\u2010induced diabetic rats: The role of toll\u2010like receptor 4 (TLR4) and mir146a"],"prefix":"10.1002","volume":"37","author":[{"given":"Roya","family":"Naderi","sequence":"first","affiliation":[{"name":"Nephrology and Kidney Transplant Research Center, Clinical Research Institute Urmia University of Medical Sciences  Urmia Iran"},{"name":"Department of Physiology, School of Medicine Urmia University of Medical Sciences  Urmia Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bagher","family":"Pourheydar","sequence":"additional","affiliation":[{"name":"Neurophysiology Research Center Urmia University of Medical Sciences  Urmia Iran"},{"name":"Department of Anatomical Sciences, Faculty of Medicine Urmia University of Medical Sciences  Urmia Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1153-1475","authenticated-orcid":false,"given":"Azam","family":"Moslehi","sequence":"additional","affiliation":[{"name":"Cellular &amp; Molecular Research Center Qom University of Medical Sciences  Qom Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-1962"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00268"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-17-0390"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2017.40"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2015.04.004"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/157339912803529887"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2185"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.03.023"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-020-01957-4"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106967"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.10.036"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117365"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2019.04.010"},{"key":"e_1_2_8_16_1","author":"Bahreini F.","year":"2021","journal-title":"Curr. Diabetes Rev."},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209414109"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0212063"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2222"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2020.61.8.660"},{"issue":"1","key":"e_1_2_8_21_1","first-page":"29","volume":"21","author":"Song G.","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0398-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aev352"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12522"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.21037\/cco.2019.11.02"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-017-9976-5"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.05.001"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12141"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13565"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-020-00146-7"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.13278"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.109332"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12373"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053203"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40200-020-00711-0"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.18502\/ijrm.v19i8.9619"},{"issue":"12","key":"e_1_2_8_37_1","first-page":"1091","volume":"19","author":"Pourheydar B.","year":"2021","journal-title":"Int. J. Reprod. Biomed."},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.658432"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-022-00198-7"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2021.651286"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-021-00919-3"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2016.1231202"},{"key":"e_1_2_8_43_1","author":"Oliveira J. S.","year":"2016","journal-title":"Brazilian J. Biol."},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c01823"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.14185"},{"issue":"7","key":"e_1_2_8_46_1","first-page":"589","volume":"19","author":"Solgi T.","year":"2021","journal-title":"Int. J. Reprod. Biomed."},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-021-00851-9"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-022-03016-9"},{"key":"e_1_2_8_49_1","author":"Hou F.","year":"2022","journal-title":"Genes. Genomics."},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-021-00370-8"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105941"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-21223"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1166\/jnn.2021.18645"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-021-02591-8"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13631"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573399815666191115154421"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.23272","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.23272","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.23272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T22:53:46Z","timestamp":1692658426000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.23272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,12]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/jbt.23272"],"URL":"https:\/\/doi.org\/10.1002\/jbt.23272","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,12]]},"assertion":[{"value":"2022-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23272"}}