Carnosol attenuates bleomycin-induced lung damage via suppressing fibrosis, oxidative stress and inflammation in rats

Life Sci. 2021 Dec 15:287:120059. doi: 10.1016/j.lfs.2021.120059. Epub 2021 Oct 30.

Abstract

Aims: Bleomycin, an important toxic anti-cancer agent, induces pulmonary fibrosis. The significance of oxidative stress and inflammation in promoting of bleomycin-induced idiopathic pulmonary fibrosis (IPF) has been reported. Thus, we evaluated the protective effects of carnosol as a robust natural antioxidant and anti-inflammatory agent for bleomycin-related IPF in rats.

Main methods: Male Wistar rats (n = 40) were randomly assigned to five groups. Group 1 was administrated with saline (intratracheally) on day 7 and oral gavage of dimethyl sulfoxide (DMSO, 0.05%) from day 1 to day 28. Group 2 received a single dose of bleomycin (intratracheally, 7.5 UI/kg) on day 7 and oral gavage of saline for 28 days. Groups 3, 4 and 5 were administrated with bleomycin (single dose) on day 7, along with oral administration of carnosol (at doses 10, 20 and 40 mg/kg, respectively) from day 1 to day 28. The lungs were isolated to measure the histopathological and biochemical and inflammatory markers.

Key findings: Carnosol treatment significantly reduced malondialdehyde, nitric oxide, protein carbonyl, tumor necrosis factor- α, interleukin-6 levels and myeloperoxidase activity in the lungs of rats exposed to bleomycin. Also, lung glutathione content, catalase, glutathione peroxidase and superoxide dismutase activities significantly increased in the carnosol/bleomycin-treated group than the bleomycin group. Lung index, hydroxyproline content, fibrosis and histopathological changes, also significantly decreased by carnosol therapy.

Significance: Treatment with carnosol can modulate biochemical and histological alterations caused by bleomycin. Thus, it can be regarded as an appropriate therapeutic approach for IPF.

Keywords: Anti-inflammation; Anti-oxidant; Bleomycin; Carnosol; Idiopathic pulmonary fibrosis.

MeSH terms

  • Abietanes / pharmacology
  • Abietanes / therapeutic use*
  • Animals
  • Antibiotics, Antineoplastic / toxicity
  • Bleomycin / toxicity*
  • Dose-Response Relationship, Drug
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy*
  • Pneumonia / metabolism
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / metabolism
  • Rats
  • Rats, Wistar
  • Rosmarinus

Substances

  • Abietanes
  • Antibiotics, Antineoplastic
  • Bleomycin
  • carnosol