ArticleJournal of research in medical sciences : the official journal of Isfahan University of Medical Sciences2023
Effect of troxerutin on the expression of genes regulating mitochondrial biogenesis and microRNA-140 in doxorubicin-induced testicular toxicity.
Article in Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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6 authors at 1 institution in 1 country.
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Abstract
Background: 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). Materials and Methods: Twenty-four adult male Wistar rats (250-300 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. Results: 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 ( Conclusion: Reduction of DOX-induced testicular toxicity following TXR pretreatment was associated with upregulation of SIRT-1/PGC-1α/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.
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