Carvacrol protects rats against bleomycin-induced lung oxidative stress, inflammation, and fibrosis

Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):10075-10089. doi: 10.1007/s00210-024-03273-7. Epub 2024 Jul 8.

Abstract

The main objective of this study was to investigate the potential efficacy of carvacrol (CAR) in mitigating bleomycin (BLM)-induced pulmonary fibrosis (PF). Sixty-six male Wistar rats were assigned into two main groups of 7 and 21 days. They were divided into the subgroups of control, BLM, CAR 80 (only for the 21-day group), and CAR treatment groups. The CAR treatment groups received CAR (20, 40, and 80 mg/kg, orally) for 7 or 21 days after an instillation of BLM (5 mg/kg, intratracheally). Results indicated that BLM significantly increased total cell count in bronchoalveolar lavage fluid and the percentages of neutrophils and lymphocytes, and reduced the percentage of macrophages. CAR dose-dependently decreased total cell count and the percentage of neutrophils and lymphocytes. CAR significantly reduced thiobarbituric acid reactive substances and hydroxyproline levels and elevated the total thiol level and catalase, superoxide dismutase, and glutathione peroxidase activities in BLM-exposed rats. Furthermore, CAR decreased the transforming growth factor-β1, connective transforming growth factor, and tumor necrosis factor-α on days 7 and 21. BLM increased interferon-γ on day 7 but decreased its level on day 21. However, CAR reversed interferon-γ levels on days 7 and 21. Based on histopathological findings, BLM induced inflammation on days 7 and 21, but for induction of fibrosis, 21-day study showed more fibrotic injuries than the 7-day group. CAR showed the improvement of fibrotic injuries. The effect of CAR against BLM-induced pulmonary fibrosis is possibly due to its antioxidant, anti-inflammatory, and antifibrotic activity.

Keywords: Anti-inflammatory; Antifibrotic; Antioxidant; Bleomycin; Carvacrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Bleomycin* / toxicity
  • Bronchoalveolar Lavage Fluid* / chemistry
  • Bronchoalveolar Lavage Fluid* / cytology
  • Cymenes* / pharmacology
  • Cymenes* / therapeutic use
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Monoterpenes / pharmacology
  • Monoterpenes / therapeutic use
  • Oxidative Stress* / drug effects
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / drug therapy
  • Pulmonary Fibrosis* / metabolism
  • Pulmonary Fibrosis* / pathology
  • Pulmonary Fibrosis* / prevention & control
  • Rats
  • Rats, Wistar*

Substances

  • carvacrol
  • Cymenes
  • Bleomycin
  • Antioxidants
  • Monoterpenes
  • Anti-Inflammatory Agents