Preventive effect of melatonin on bleomycin-induced lung fibrosis in rats

J Pineal Res. 2006 Jan;40(1):27-33. doi: 10.1111/j.1600-079X.2005.00272.x.


Oxidative stress has an important role in the pathogenesis of idiopathic pulmonary fibrosis. Melatonin has direct and indirect free radical-detoxifying activity. The present study investigated whether melatonin treatment attenuates bleomycin-induced lung fibrosis in rats. A group of rats was given one dose of bleomycin while the control animals were given saline. The first dose of melatonin (4 mg/kg/day) was given 2 days before the bleomycin injection. At day 14, fibrotic changes were evaluated using Aschoft's criteria and lung hydroxyproline content. Bleomycin produced a 2.7-fold rise in the fibrosis score that was decreased 65% by melatonin (P < 0.05) and a 1.4-fold increase in hydroxyproline content which was completely prevented by melatonin. Protein carbonyl and thiobarbituric acid reactive substances levels, which were significantly elevated in the bleomycin treated rats, were significantly attenuated by melatonin. Bleomycin administration significantly reduced the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissue. The reduction in CAT activity was prevented by melatonin but SOD and GSH-Px were not influenced. These results revealed that melatonin may prevent the development of bleomycin-induced lung fibrosis via the repression of protein and lipid peroxidation.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Bleomycin
  • Bronchoalveolar Lavage Fluid / cytology
  • Disease Models, Animal
  • Hydroxyproline / analysis
  • Lung / pathology
  • Male
  • Malondialdehyde / analysis
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Peroxidase / analysis
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control*
  • Rats
  • Rats, Wistar


  • Antioxidants
  • Bleomycin
  • Malondialdehyde
  • Peroxidase
  • Melatonin
  • Hydroxyproline