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The protective effects of hesperidin and curcumin on 5-fluorouracil–induced nephrotoxicity in mice

Abstract

Nephrotoxicity is a very important complication of 5-fluorouracil (5-FU)–treated cancer patients. Increased oxidative stress, kidney damage, and apoptosis play an important role in the pathogenesis of nephrotoxicity caused by 5-FU. In this study, protective effects of two natural compounds, hesperidin and curcumin, on experimentally induced kidney damage in mice with 5-FU were determined. Application of 5-FU resulted in severe histopathological changes and severe renal failure with increased serum urea and creatinine levels. Also, 5-FU–induced kidney damage, increased levels of malondialdehyde (MDA), decreased superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) activity, and glutathione (GSH) level have been demonstrated. Also, where 5-FU is in the concentration of caspase-3 and 8-OHdG immune-positive cells and therefore causes apoptosis and DNA damage in kidney tissue cells. However, especially high doses of hesperidin and curcumin treatment significantly improved 5-FU–induced oxidative stress/lipid peroxidation, apoptosis/DNA damage, and renal dysfunction. Based on these data, our results suggest that hesperidin and curcumin may be used as new and promising agents against 5-FU–induced nephrotoxicity.

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VG, EŞ, ST, AK: experiment design, experiment application, samples collection. VG, EŞ, ES: serum markers and tissue antioxidant estimation, data curation and analysis, final reviewing. SY: histopathological and immunohistochemical investigation. All the authors contributed to the writing and editing, and they read and approved the final manuscript.

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Correspondence to Volkan Gelen.

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The study was designed and conducted according to ethical norms approved by the Atatürk University Rectorate Animal Experiments Local Ethics Committee (Erzurum, Turkey) (Protocol No. 2019/16).

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Gelen, V., Şengül, E., Yıldırım, S. et al. The protective effects of hesperidin and curcumin on 5-fluorouracil–induced nephrotoxicity in mice. Environ Sci Pollut Res 28, 47046–47055 (2021). https://doi.org/10.1007/s11356-021-13969-5

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  • DOI: https://doi.org/10.1007/s11356-021-13969-5

Keywords

  • Nephrotoxicity
  • Apoptosis
  • Curcumin
  • Hesperidin
  • Histopathology
  • Immunohistochemistry
  • Mice