Caffeic acid phenethyl ester as a protective agent against doxorubicin nephrotoxicity in rats

Clin Chim Acta. 2004 Oct;348(1-2):27-34. doi: 10.1016/j.cccn.2004.03.035.


Background: Nephrotoxicity is one of the important side effects of antracycline antibiotics. The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, against nephrotoxicity induced by doxorubicin (DXR).

Methods: The rats were divided into control, CAPE alone, doxorubicin (20 mg/kg, i.p.) and doxorubicin plus CAPE (10 micromol/kg/day, i.p.) groups. At the end of the 10th day, kidney tissues were removed for light microscopy and analysis. The levels of tissues protein carbonyl content (PC), malondialdehyde (MDA) and nitric oxide (NO) as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) were determined. Plasma oxidants and antioxidants were also measured.

Results: The activities of CAT and GSH-Px were decreased as well as myeloperoxidase, NO, MDA and PC were increased in renal tissue of doxorubicin group compared with the other groups. Plasma GSH-Px activity was higher in doxorubicin plus CAPE group than the others and plasma MDA level was higher in doxorubicin group than the other groups. There were glomerular vacuolization, tubular desquamation, loss of brush border, and adhesion to Bowman's in the light microscopy in the kidneys of doxorubicin group. The tubules and brush border were almost normal and some of the glomerulus was filled with fine vacuoles in CAPE treated rats.

Conclusion: Doxorubicin caused renal injury and CAPE treatment prevented lipid peroxidation and protein oxidation in renal tissue and partially preserved glomerulus and tubules.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Caffeic Acids / pharmacology
  • Caffeic Acids / therapeutic use*
  • Doxorubicin / toxicity*
  • Drug Interactions
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / prevention & control*
  • Lipid Peroxidation
  • Male
  • Nitric Oxide / metabolism
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology
  • Phenylethyl Alcohol / therapeutic use*
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley


  • Antioxidants
  • Caffeic Acids
  • Protective Agents
  • Nitric Oxide
  • Doxorubicin
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol