Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage

Phytomedicine. 2013 Mar 15;20(5):453-60. doi: 10.1016/j.phymed.2012.12.001. Epub 2013 Jan 23.


Nephrotoxicity is an important complication in cancer patients undergoing cisplatin therapy. Oxidative stress, inflammation and apoptosis/necrosis are the major patho-mechanisms of cisplatin induced nephrotoxicity. In the present study, hesperidin, a naturally-occurring bioflavonoid has been demonstrated to have protective effect on cisplatin-induced renal injury in rats. Cisplatin intoxication resulted in structural and functional renal impairment which was revealed by massive histopathological changes and elevated blood urea nitrogen and serum creatinine levels, respectively. Renal injury was associated with oxidative stress/lipid peroxidation as evident by increased reactive oxygen species (ROS) and malondialdehyde (MDA) formation with decreased levels of antioxidants such as reduced glutathione, vitamin C, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase. Cisplatin administration also triggered inflammatory response in rat kidneys by inducing pro-inflammatory cytokine, TNF-α, with the increased expression of myeloperoxidase (MPO). Furthermore, cisplatin increased the activity of caspase-3 and DNA damage with decreased tissue nitric oxide levels. Hesperidin treatment significantly attenuated the cisplatin-induced oxidative stress/lipid peroxidation, inflammation (infiltration of leukocytes and pro-inflammatory cytokine), apoptosis/necrosis (caspase-3 activity with DNA damage) as well as increased expression of nitric oxide in the kidney and improved renal function. Thus, our results suggest that hesperidin co-administration may serve as a novel and promising preventive strategy against cisplatin-induced nephrotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Animals
  • Apoptosis / drug effects
  • Blood Urea Nitrogen
  • Caspase 3 / chemistry
  • Cisplatin / adverse effects*
  • Creatinine / blood
  • Cytoprotection
  • DNA Damage*
  • Glutathione / chemistry
  • Glutathione Peroxidase / chemistry
  • Glutathione Reductase / chemistry
  • Hesperidin / chemistry
  • Hesperidin / therapeutic use*
  • Inflammation / drug therapy*
  • Kidney / chemistry
  • Kidney / drug effects
  • Kidney / enzymology
  • Kidney / pathology
  • Lipid Peroxidation
  • Male
  • Malondialdehyde / chemistry
  • Nitric Oxide / chemistry
  • Oxidative Stress / drug effects*
  • Peroxidase / chemistry
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / chemistry
  • Superoxide Dismutase / chemistry
  • Tumor Necrosis Factor-alpha / chemistry


  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Malondialdehyde
  • Creatinine
  • Hesperidin
  • Peroxidase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Casp3 protein, rat
  • Caspase 3
  • Glutathione
  • Cisplatin