Tektemur, AhmetKaya Tektemur, NalanErdem Güzel, Elif2022-02-172022-02-172022Tektemur A, Tektemur N. K, Erdem Güzel, E. (2022). The therapeutic effect of hesperetin on doxorubicin-induced testicular toxicity: Potential roles of the mechanistic target of rapamycin kinase (mTOR) and dynamin-related protein 1 (DRP1). Toxicol Appl Pharmacol. 2022 Jan 15;435:115833. doi: 10.1016/j.taap.2021.115833. Epub 2021 Dec 18. PMID: 34933056.https://doi.org/10.1016/j.taap.2021.115833https://pubmed.ncbi.nlm.nih.gov/34933056/https://www.scopus.com/record/display.uri?eid=2-s2.0-85121462293&origin=resultslist&sort=plf-f&src=s&st1=10.1016%2fj.taap.2021.115833&sid=68ed00a61399911207549882758f1206&sot=b&sdt=b&sl=31&s=DOI%2810.1016%2fj.taap.2021.115833%29&relpos=0&citeCnt=0&searchTerm=&featureToggles=FEATURE_NEW_DOC_DETAILS_EXPORT:1https://hdl.handle.net/20.500.12514/3055https://www.webofscience.com/wos/woscc/full-record/WOS:000789897500005?AlertId=d383397b-4355-449e-9419-70f9e0e77c15&SID=EUW1ED0F6Fvvo5bcqnHH9fm5GBBQKClinical utilization of doxorubicin (DOX), which is a commonly used chemotherapeutic, is restricted due to toxic effects on various tissues. Using hesperetin (HST), an antioxidant used in Chinese traditional medicine protects testis against DOX-induced toxicity although the molecular mechanisms are not well-known. The study was aimed to examine the possible role of the mechanistic target of rapamycin kinase (mTOR) and dynamin 1-like dynamin-related protein 1 (DRP1) in the therapeutic effects of HST on the DOX-induced testicular toxicity. Rats were divided into Control, DOX, DOX + HST, and HST groups (n = 7). Single-dose DOX (15 mg/kg) was administered intraperitoneally and HST (50 mg/kg) was administered by oral gavage every other day for 28 days. Total antioxidant status (TAS), histopathological evaluations, immunohistochemistry, and gene expression level detection analyses were performed. Histopathologically, DOX-induced testicular damage was ameliorated by HST treatment. DOX reduced testicular TAS levels and increased oxidative stress markers, 8-Hydroxy-deoxyguanosine (8-OHdG), and 4-Hydroxynonenal (4-HNE). Also, upregulated mTOR and DRP1 expressions with DOX exposure were decreased after HST treatment in the testis (p < 0.05). On the other hand, DOX-administration downregulated miR-150-5p and miR-181b-2-3p miRNAs, targeting mTOR and mRNA levels of beclin 1 (BECN1) and autophagy-related 5 (ATG5), autophagic markers. Furthermore, these levels were nearly similar to control testis samples in the DOX + HST group (p < 0.05). The study demonstrated that HST may have a therapeutic effect on DOX-induced testicular toxicity by removing reactive oxygen species (ROS) and by modulating the mTOR and DRP1 expressions, which have a critical role in regulating the balance of generation/elimination of ROS.en10.1016/j.taap.2021.115833info:eu-repo/semantics/closedAccessDRP1; Doxorubicin; Hesperetin; Testis; mTOR.Article435Q2N/AWOS:0007898975000052-s2.0-8512146229334933056