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Metformin enhanced the effect of pirfenidone on pulmonary fibrosis in mice
Nana Liu1, Yanqiu Song2, Ting Liu2
1Department of Critical Care Medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China.
Background:
The aim of the study is to observe the anti-inflammatory and antioxidative stress effects of metformin on bleomycin (BLM)-induced pulmonary fibrosis in mice.
Methods:
Mice with BLM-induced pulmonary fibrosis were treated with pirfenidone, metformin, pirfenidone plus metformin and the NADPH oxidase 4 (NOX4) inhibitor diphenyleneiodonium chloride (DPI). Pathological changes and hydroxyproline (HPO) levels were examined in the lung tissue of mice with pulmonary fibrosis. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) levels in lung tissue were determined.
Results:
Compared with pirfenidone, pirfenidone plus metformin could reduce alveolar damage and collagen fibre deposition and alleviate BLM-induced pulmonary fibrosis. Lung HPO levels were significantly lower in the PFD + MET group than in the BLM group (p < 0.05). SOD levels in the lungs of mice were increased in the PFD + MET group than in the BLM group (p < 0.05). Metformin and pirfenidone plus metformin can reduce MDA levels (p < 0.05). Pirfenidone plus metformin could reduce HPO levels, increase SOD levels, and reduce MDA levels in the lungs of mice. There was a significant correlation between the HPO level and the Ashcroft score (r = 0.520, p < 0.001).
Conclusion:
Metformin enhanced the antifibrotic effects of pirfenidone on BLM-treated mice. Moreover, these findings provide an experimental basis for examining whether metformin can improve the antifibrotic effects of pirfenidone on patients with idiopathic pulmonary fibrosis (IPF). It has broad therapeutic prospects for patients with IPF.
Insights
Metformin enhances pirfenidone's antifibrotic effects in bleomycin-induced pulmonary fibrosis in mice. This combination therapy shows promise for treating idiopathic pulmonary fibrosis (IPF).
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Fibrosis Research
Background:
- Pulmonary fibrosis is a debilitating lung disease.
- Bleomycin (BLM)-induced pulmonary fibrosis in mice serves as a model for studying antifibrotic therapies.
- Metformin's anti-inflammatory and antioxidative stress effects are being investigated for their potential in treating pulmonary fibrosis.
Purpose of the Study:
- To evaluate the anti-inflammatory and antioxidative effects of metformin in BLM-induced pulmonary fibrosis.
- To determine if metformin enhances the antifibrotic efficacy of pirfenidone.
Main Methods:
- Mice were induced with BLM to develop pulmonary fibrosis.
- Treatment groups included pirfenidone, metformin, pirfenidone plus metformin, and a NADPH oxidase 4 (NOX4) inhibitor (DPI).
- Lung tissue was analyzed for pathological changes, hydroxyproline (HPO) levels, superoxide dismutase (SOD) activity, and malonaldehyde (MDA) levels.
Main Results:
- Pirfenidone plus metformin significantly reduced alveolar damage and collagen deposition compared to pirfenidone alone.
- Lung HPO and MDA levels were decreased, while SOD levels were increased in the combined treatment group.
- A significant correlation was observed between HPO levels and the Ashcroft score for fibrosis.
Conclusions:
- Metformin potentiates the antifibrotic effects of pirfenidone in a mouse model of pulmonary fibrosis.
- These findings suggest that metformin could be a valuable adjunct therapy for patients with idiopathic pulmonary fibrosis (IPF).
- Further clinical investigation is warranted to explore metformin's therapeutic potential in IPF patients.
