Thymol protects against bleomycin-induced pulmonary fibrosis via abrogation of oxidative stress, inflammation, and modulation of miR-29a/TGF-β and PI3K/Akt signaling in mice

Life Sci. 2023 Feb 1:314:121256. doi: 10.1016/j.lfs.2022.121256. Epub 2022 Dec 20.

Abstract

Idiopathic pulmonary fibrosis is a terminal lung ailment that shares several pathological and genetic mechanisms with severe COVID-19. Thymol (THY) is a dietary compound found in thyme species that showed therapeutic effects against various diseases. However, the effect of THY against bleomycin (BLM)-induced lung fibrosis was not previously investigated. The current study investigated the ability of THY to modulate oxidative stress, inflammation, miR-29a/TGF-β expression, and PI3K/phospho-Akt signaling in lung fibrosis. Mice were divided into Normal, THY (100 mg/kg, p.o.), BLM (15 mg/kg, i.p.), BLM + THY (50 mg/kg, p.o.), and BLM + THY (100 mg/kg, p.o.) groups and treated for four weeks. The obtained results showed that BLM + THY (50 mg/kg) and BLM + THY (100 mg/kg) reduced fibrotic markers; α-SMA and fibronectin, inflammatory mediators; TNF-α, IL-1β, IL-6, and NF-kB and oxidative stress biomarkers; MDA, GSH, and SOD, relative to BLM group. Lung histopathological examination by H&E and Masson's trichrome stains confirmed the obtained results. Remarkably, expression levels of TGF-β, PI3K, and phospho-Akt were decreased while miR-29a expression was elevated. In conclusion, THY effectively prevented BLM-induced pulmonary fibrosis by exerting significant anti-oxidant and anti-inflammatory effects. Our novel findings that THY upregulated lung miR-29a expression while decreased TGF-β and PI3K/Akt signaling are worthy of further investigation as a possible molecular mechanism for THY's anti-fibrotic actions.

Keywords: Antioxidant; Fibrosis; Inflammation; Lung; MicroRNA; Thymol.

MeSH terms

  • Animals
  • Bleomycin / toxicity
  • COVID-19* / pathology
  • Fibrosis
  • Inflammation / metabolism
  • Lung / metabolism
  • Mice
  • MicroRNAs* / metabolism
  • Oxidative Stress
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / drug therapy
  • Pulmonary Fibrosis* / genetics
  • Thymol / therapeutic use
  • Transforming Growth Factor beta / metabolism

Substances

  • Bleomycin
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Thymol
  • Transforming Growth Factor beta
  • MicroRNAs