Ellagic acid attenuates bleomycin and cyclophosphamide-induced pulmonary toxicity in Wistar rats

Food Chem Toxicol. 2013 Aug:58:210-9. doi: 10.1016/j.fct.2013.03.046. Epub 2013 Apr 17.


Use of bleomycin (BLM) and cyclophosphamide (CP) as chemotherapeutic drugs is associated with side effects including toxicity to respiratory system. Their co-administration may enhance lung toxicity which may subsequently progress to the lung fibrosis. Natural compounds have shown mitigating effects against toxicity of anticancer drugs. Ellagic acid (EA), a polyphenolic compound present in many fruits and nuts in addition to walnut has shown promising protective effect against toxicity of drugs and chemicals. We studied the ameliorative effect of EA on lung toxicity in rats exposed to CP (150 mg/kg b.w., i.p.) and BLM (10 U/kg b.w., i.t.). EA (15 mg/kg b.w., p.o.×14 days) treatment modulated enhanced hydroxyproline level, lipid peroxidation, myeloperoxidase activity, nitric oxide production and protein carbonyl formation in lungs of rats exposed to toxic anticancer drugs. There was a marked decrease in GSH content and activities of antioxidant enzymes as a result of BLM and CP treatment. Bronchoalveolar lavage fluid showed increased level of cytotoxicity markers in drug treated animals. Treatment with EA attenuated these changes. Histopathological findings also showed protective effects of EA. In conclusion, EA emerged as a natural protectant with an ability to protect lungs from onslaught of pulmonary toxicity of anticancer drugs.

Keywords: BALF; BLM; Bleomycin; Bronchoalveolar lavage fluid; CP; Cyclophosphamide; EA; Ellagic acid; GPx; GR; GSH; GST; LPO; Oxidative stress; Pulmonary toxicity; ROS; bleomycin; bronchoalveolar lavage fluid; cyclophosphamide; ellagic acid; glutathione S-transferase; glutathione peroxidase; glutathione reductase; lipid peroxidation; reactive oxygen species; reduced glutathione.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Biomarkers / metabolism
  • Bleomycin / toxicity*
  • Bronchoalveolar Lavage Fluid
  • Cyclophosphamide / toxicity*
  • Ellagic Acid / pharmacology*
  • Lung / drug effects*
  • Male
  • Rats
  • Rats, Wistar


  • Antineoplastic Agents
  • Biomarkers
  • Bleomycin
  • Ellagic Acid
  • Cyclophosphamide