MELATONIN ALLEVIATES BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN MICE

J Biol Regul Homeost Agents. Apr-Jun 2015;29(2):327-34.

Abstract

Pulmonary fibrosis occurs as a common end-stage sequela of a number of acute and chronic lung diseases. Eicosanoids exert crucial roles in inflammatory processes pertinent to fibrogenesis induction, however, the role of cyclooxygenase 2 (COX-2) is not fully elucidated in most pulmonary fibrosis related-disorders. Recently, melatonin (MLN) has been introduced as an effective immuno-modulator and anti-oxidant agent. The present study aimed to investigate the effect of MLN on COX-2 expression in idiopathic pulmonary fibrosis (IPF). Animals were divided into five groups, including: 1) saline control, 2) 1% ethanol control, 3) MLN control, 4) bleomycin (BLM), in which mice were injected with BLM (15 mg/kg, i.p.) two times per week for four weeks, and 5) BLM+MLN, in which MLN was given to mice (10 mg/kg, i.p.) 30 minutes prior to BLM injections for four weeks. MLN administration significantly reduced body weight loss (P<0.05), the rate of mortality, edema formation, lung injury, COX-2 expression (P>0.05), interstitial tissue percentage volume (P<0.05), and also increased the alveolar space percentage volume. MLN attenuated the BLM-induced lung injury responses such as collagen accumulation and airway dysfunction in mice. Finally, histological evidence supported the ability of MLN to inhibit COX-2 expression. Thus, it may serve as a novel potential therapeutic agent for IPF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Bleomycin / toxicity*
  • Body Weight / drug effects
  • Cyclooxygenase 2 / analysis
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Drug Evaluation, Preclinical
  • Enzyme Induction / drug effects
  • Lung / enzymology
  • Male
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology
  • Pulmonary Edema / prevention & control
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / enzymology
  • Pulmonary Fibrosis / pathology

Substances

  • Antioxidants
  • Cyclooxygenase 2 Inhibitors
  • Bleomycin
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Melatonin