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.
Highlights
Acute lung injury (ALI) is a life-threatening pulmonary syndrome with high incidence and mortality worldwide and is the most serious form of lung injury caused by the current pandemic coronavirus disease 2019 (COVID-19) (Peck and Hibbert, 2019; Peritore et al, 2021)
To determine whether fluorofenidone has a protective effect on ALI, we evaluated the histopathologic feature of the lungs in the LPSinduced ALI mouse model
We found that fluorofenidone treatment significantly diminished the elevated levels of IL-1β, tumor necrosis factor-α (TNF-α), and MCP-1 in BALF of LPSinduced ALI mice (Figures 2A–C)
Summary
Acute lung injury (ALI) is a life-threatening pulmonary syndrome with high incidence and mortality worldwide and is the most serious form of lung injury caused by the current pandemic coronavirus disease 2019 (COVID-19) (Peck and Hibbert, 2019; Peritore et al, 2021). The leading causes of ALI include bacterial infection, acid inhalation, fatty embolism, or virus infection. The main characteristics of ALI are excessive pulmonary inflammatory cell infiltration, diffuse alveolar damage, pulmonary epithelial cell apoptosis, and pulmonary edema, which led to reduction in tissue oxygenation and respiratory failure (Zhang et al, 2016; Silva et al, 2020). No satisfactory pharmacological therapies have been approved to lower ALI patients’ mortality. Developing an effective, preventive, and therapeutic drug to improve clinical prognosis is necessary.
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