Naringenin mitigates 5-fluorouracil-induced nephrotoxicity by decreasing oxidative stress, inflammation and apoptosis

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.