Coenzyme Q10 Alleviates Silicosis Fibrosis via Inhibiting Ferroptosis in Mice

In Vivo. 2025 Jan-Feb;39(1):180-189. doi: 10.21873/invivo.13816.

Abstract

Background/aim: Silicosis, the most severe type of occupational pneumoconiosis, leads to diffuse pulmonary fibrosis without specific therapy. Ferroptosis is triggered by reactive oxygen species (ROS) and Fe2+ overload-induced lipid peroxidation, which is involved in the progression of pulmonary fibrosis. As an important coenzyme in the process of aerobic respiration, Coenzyme Q10 (CoQ10) can enhance mitochondrial function and energy supply and reduce malondialdehyde (MDA) to limit the risk of fibrosis. We aimed to clarify whether ferroptosis is involved in the process of coenzyme CoQ10-treated silicosis fibrosis.

Materials and methods: C57BL/6J mice were divided in 3 groups (n=6 in each group). In the normal group, mice underwent sham operation; in the silicosis group, mice were tracheally instilled with SiO2 suspension; in CoQ10 group, mice with silicosis were treated with CoQ10 solution. Histological analyses were performed to assess the lung injury level. Iron content was measured by colorimetry in lung tissue. The levels of MDA in lung tissue were characterized by immunofluorescence staining. The level of alpha smooth muscle actin (α-SMA), Collagen I, GPX4, p53 expression was analyzed by qRT-PCR and western blotting.

Results: CoQ10 significantly reduced the mRNA and protein expression levels of α-SMA and collagen I in silicosis lung tissues. It is worth noting that CoQ10 significantly inhibited the accumulation of lipid peroxidation and Fe2+ level by increasing the expression of ferroptosis regulatory core enzyme GPX4 and reducing its upstream regulator p53 in silicosis lung tissues.

Conclusion: CoQ10 alleviated silicosis fibrosis via inhibiting ferroptosis in mice. This finding is a new perspective for exploring the pathogenesis and treatment for silicosis.

Keywords: Silicosis fibrosis; coenzyme Q10; ferroptosis; pneumoconiosis; pulmonary fibrosis.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Disease Models, Animal*
  • Ferroptosis* / drug effects
  • Iron / metabolism
  • Lipid Peroxidation / drug effects
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Phospholipid Hydroperoxide Glutathione Peroxidase / genetics
  • Phospholipid Hydroperoxide Glutathione Peroxidase / metabolism
  • Pulmonary Fibrosis* / drug therapy
  • Pulmonary Fibrosis* / etiology
  • Pulmonary Fibrosis* / metabolism
  • Pulmonary Fibrosis* / pathology
  • Reactive Oxygen Species / metabolism
  • Silicosis* / drug therapy
  • Silicosis* / metabolism
  • Silicosis* / pathology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquinone* / analogs & derivatives
  • Ubiquinone* / pharmacology

Substances

  • Ubiquinone
  • coenzyme Q10
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Actins
  • glutathione peroxidase 4, mouse
  • Tumor Suppressor Protein p53
  • Malondialdehyde
  • Reactive Oxygen Species
  • Collagen Type I
  • alpha-smooth muscle actin, mouse
  • Iron