Effect of blueberry pretreatment on diethylnitrosamine-induced oxidative stress and liver injury in rats

Environ Toxicol Pharmacol. 2013 Sep;36(2):529-538. doi: 10.1016/j.etap.2013.05.014. Epub 2013 Jun 10.


Diethylnitrosamine (DEN) treatment increases the generation of reactive oxygen species (ROS), apoptosis, necrosis and proliferation in the liver. Blueberries (BB; Vaccinium corymbosum L.) contain polyphenols and other active components and have high antioxidant capacities. We investigated the effect of BB pretreatment on DEN-induced liver injury and oxidative and nitrosative stress in male rats. Rats were fed with 5% and 10% BB containing diet for six weeks and DEN (200mg/kg; i.p.) was applied two days before the end of this period. Liver function tests were determined in serum and histopathological evaluation was performed in the liver tissue. Apoptosis-related proteins, Bax and B cell lymphoma-2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) expressions were also examined. Oxidative and nitrosative stress were evaluated in the liver by measuring thiobarbituric acid reactive substances, diene conjugate, protein carbonyl and nitrotyrosine levels, and glutathione levels and glutathione peroxidase, superoxide dismutase and glutathione transferase (GST) activities. Pretreatment with high dose of BB reduced apoptotic, necrotic and proliferative changes in the liver induced by DEN. Dietary BB also decreased hepatic lipid peroxidation, protein oxidation and nitrotyrosine levels together with increased GST activity. In conclusion, BB may have an inhibiting effect on acute liver injury by reducing apoptosis, necrosis, proliferation, oxidative and nitrosative stress in DEN-treated rats.

Keywords: Blueberry; Diethylnitrosamine; Hepatic injury; Oxidative stress; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Blueberry Plants*
  • Cell Proliferation / drug effects
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Diethylnitrosamine*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Fruit
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Necrosis
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Plant Extracts / administration & dosage*
  • Plants, Medicinal
  • Protein Carbonylation / drug effects
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Time Factors
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • Antioxidants
  • Biomarkers
  • Plant Extracts
  • Thiobarbituric Acid Reactive Substances
  • 3-nitrotyrosine
  • Diethylnitrosamine
  • Tyrosine
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Transferase
  • Glutathione