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Protective Effect of Fluorofenidone Against Acute Lung Injury Through Suppressing the MAPK/NF-κB Pathway
Xin Lv1, Tingting Yao2, Rongling He2
1Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Acute lung injury (ALI) is a severe disease that presents serious damage and excessive inflammation in lungs with high mortality without effective pharmacological therapy. Fluorofenidone (AKFPD) is a novel pyridone agent that has anti-fibrosis, anti-inflammation, and other pharmacological activities, while the effect of fluorofenidone on ALI is unclarified. Here, we elucidated the protective effects and underlying mechanism of fluorofenidone on lipopolysaccharide (LPS)-induced ALI. In this study, fluorofenidone alleviated lung tissue structure injury and reduced mortality, decreased the pulmonary inflammatory cell accumulation and level of inflammatory cytokines IL-1β, IL-6, and TNF-α in the bronchoalveolar lavage fluid, and attenuated pulmonary apoptosis in LPS-induced ALI mice. Moreover, fluorofenidone could block LPS-activated phosphorylation of ERK, JNK, and P38 and further inhibited the phosphorylation of IκB and P65. These results suggested that fluorofenidone can significantly contrast LPS-induced ALI through suppressing the activation of the MAPK/NF-κB signaling pathway, which indicates that fluorofenidone could be considered as a novel therapeutic candidate for ALI.
Insights
Fluorofenidone effectively treats acute lung injury (ALI) by reducing inflammation and lung damage. This novel agent protects against lipopolysaccharide-induced ALI by inhibiting key inflammatory signaling pathways.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Inflammation Research
Background:
- Acute lung injury (ALI) is a critical condition with high mortality and limited therapeutic options.
- Fluorofenidone (AKFPD) is a pyridone derivative with known anti-fibrosis and anti-inflammatory properties.
- The therapeutic potential of fluorofenidone in ALI remains largely unexplored.
Purpose of the Study:
- To investigate the protective effects of fluorofenidone against lipopolysaccharide (LPS)-induced ALI.
- To elucidate the underlying molecular mechanisms of fluorofenidone's action in ALI.
Main Methods:
- LPS was administered to induce ALI in a mouse model.
- Fluorofenidone treatment was evaluated for its effects on lung injury, mortality, and inflammation.
- Key signaling pathways, including MAPK and NF-κB, were analyzed via protein phosphorylation.
Main Results:
- Fluorofenidone significantly reduced lung tissue damage and mortality in LPS-induced ALI mice.
- It decreased inflammatory cell infiltration and levels of IL-1β, IL-6, and TNF-α in bronchoalveolar lavage fluid.
- Fluorofenidone inhibited the phosphorylation of ERK, JNK, P38, IκB, and P65, indicating suppression of MAPK/NF-κB signaling.
Conclusions:
- Fluorofenidone demonstrates significant protective effects against LPS-induced ALI.
- Its mechanism involves the suppression of the MAPK/NF-κB signaling pathway.
- Fluorofenidone represents a promising therapeutic candidate for treating ALI.
