{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:28:04Z","timestamp":1787761684106,"version":"build-2784847793"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"\n Background:<\/jats:title>\n Application of doxorubicin (DOX) in cancer patients is limited due to its dose-dependent toxicity to nontarget tissues such as testis and subsequent infertility. Due to limitation of our knowledge about the mechanisms of DOX toxicity in the reproductive system, reduction of DOX-induced testicular toxicity remains an actual and primary clinical challenge. Considering the potentials of troxerutin (TXR) in generating a protective phenotype in many tissues, we aimed to examine the effect of TXR on DOX-induced testicular toxicity by evaluating the histological changes and the expression of mitochondrial biogenesis genes and microRNA-140 (miR-140).<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n Twenty-four adult male Wistar rats (250\u2013300 g) were divided in groups with\/without DOX and\/or TXR. DOX was injected intraperitoneally at 6 consecutive doses over 12 days (cumulative dose: 12 mg\/kg). TXR (150 mg\/kg\/day; orally) was administered for 4 weeks before DOX challenge. One week after the last injection of DOX, testicular histopathological changes, spermatogenesis activity, and expression of mitochondrial biogenesis genes and miR-140 were determined.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n DOX challenge significantly increased testicular histopathological changes, decreased testicular expression profiles of sirtuin 1 (SIRT-1) and nuclear respiratory factor-2 (NRF-2), and increased expression of miR-140 (\n P<\/jats:italic>\n < 0.05 to\n P<\/jats:italic>\n < 0.01). Pretreatment of DOX-received rats with TXR significantly reversed testicular histopathological changes, spermatogenesis activity index, and the expression levels of SIRT-1, peroxisome proliferator-activated receptor-\u03b3 coactivator 1-alpha (PGC-1\u03b1), NRF-2, and miR-140 (\n P<\/jats:italic>\n < 0.05 to\n P<\/jats:italic>\n < 0.01).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Reduction of DOX-induced testicular toxicity following TXR pretreatment was associated with upregulation of SIRT-1\/PGC-1\u03b1\/NRF-2 profiles and better regulation of miR-140 expression. It seems that improving microRNA-mitochondrial biogenesis network can play a role in the beneficial effect of TXR on DOX-induced testicular toxicity.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/jrms.jrms_120_22","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T07:31:27Z","timestamp":1681803087000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Effect of troxerutin on the expression of genes regulating mitochondrial biogenesis and microRNA-140 in doxorubicin-induced testicular toxicity"],"prefix":"10.4103","volume":"28","author":[{"given":"Behnaz","family":"Mokhtari","sequence":"first","affiliation":[{"name":"Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran"},{"name":"Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, 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