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

Environ Sci Pollut Res Int. 2021 Sep;28(34):47046-47055. doi: 10.1007/s11356-021-13969-5. Epub 2021 Apr 22.

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.

Keywords: Apoptosis; Curcumin; Hesperidin; Histopathology; Immunohistochemistry; Mice; Nephrotoxicity.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Curcumin* / metabolism
  • Curcumin* / pharmacology
  • Fluorouracil / toxicity
  • Glutathione / metabolism
  • Hesperidin* / pharmacology
  • Humans
  • Kidney / metabolism
  • Malondialdehyde / metabolism
  • Mice
  • Oxidative Stress
  • Renal Insufficiency*
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Malondialdehyde
  • Hesperidin
  • Superoxide Dismutase
  • Glutathione
  • Curcumin
  • Fluorouracil