{"title":"Naringenin mitigates 5-fluorouracil-induced nephrotoxicity by decreasing oxidative stress, inflammation and apoptosis","authors":"Fatih Mehmet Gür , Sedat Bilgiç , İbrahim Aktaş","doi":"10.1016/j.tice.2025.103170","DOIUrl":null,"url":null,"abstract":"<div><div>The toxic effects of 5-fluorouracil (5-FU), a drug widely used in the treatment of neoplasms and primarily excreted through the urine, prompted us to investigate the protective potential of naringenin (NAR) against nephrotoxicity induced by 5-FU. In this study, 28 rats were randomly allocated to four groups: Control, NAR (100 mg/kg/day), 5-FU (150 mg/kg), and NAR + 5-FU (n = 7). After completion of the experimental procedures, blood and kidney tissues were subjected to analysis through biochemical, immunohistochemical, TUNEL, and histopathological methods. The analyses demonstrated significantly higher levels of MDA, BUN, TNF-α, caspase-3, and apoptosis in the 5-FU group compared to the control. Pathological alterations, including inflammatory cell infiltration, interstitial hemorrhage, brush border damage, epithelial desquamation, vacuolar degeneration, and basement membrane thickening, observed in the 5-FU group were largely absent in the NAR +5-FU group. In conclusion, NAR can significantly prevent the nephrotoxic effects of 5-FU due to its antioxidant, anti-inflammatory, and anti-apoptotic properties. The findings support the view that the therapeutic effects of NAR are mediated through the upregulation of Nrf2 and the downregulation of NF-κB.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103170"},"PeriodicalIF":2.5000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040816625004525","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The toxic effects of 5-fluorouracil (5-FU), a drug widely used in the treatment of neoplasms and primarily excreted through the urine, prompted us to investigate the protective potential of naringenin (NAR) against nephrotoxicity induced by 5-FU. In this study, 28 rats were randomly allocated to four groups: Control, NAR (100 mg/kg/day), 5-FU (150 mg/kg), and NAR + 5-FU (n = 7). After completion of the experimental procedures, blood and kidney tissues were subjected to analysis through biochemical, immunohistochemical, TUNEL, and histopathological methods. The analyses demonstrated significantly higher levels of MDA, BUN, TNF-α, caspase-3, and apoptosis in the 5-FU group compared to the control. Pathological alterations, including inflammatory cell infiltration, interstitial hemorrhage, brush border damage, epithelial desquamation, vacuolar degeneration, and basement membrane thickening, observed in the 5-FU group were largely absent in the NAR +5-FU group. In conclusion, NAR can significantly prevent the nephrotoxic effects of 5-FU due to its antioxidant, anti-inflammatory, and anti-apoptotic properties. The findings support the view that the therapeutic effects of NAR are mediated through the upregulation of Nrf2 and the downregulation of NF-κB.
期刊介绍:
Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed.
Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.