The Effect of Febuxostat in Murine Model of LPS-Induced Lung Injury

Abstract

Rationale: In severe COVID-19 patients, decrease of ATP production caused by mitochondrial dysfunction thought to induce the lung injury. Febuxostat, which is a therapeutic medicine for hyperuricemia, is thought to have the effect of improving mitochondrial dysfunction and enhances the production of ATP. The purpose of this study is to investigate the effect of febuxostat in LPS induced lung injury mouse model. Methods: C57BL/6 WT mice (8-12 wk-old males) were exposed to lipopolysaccharide (LPS) intratracheally to develop the murine model of LPS-induced lung injury. For the treatment, 100 μg of febuxostat was administered twice a day from 2 days before the exposure of LPS. Bronchial lavage fluid (BALF) and lung tissue were collected 24 hours and 7 days after the LPS exposure. The BALF were analyzed for total and differential cell counts. The lung tissues were stained with Masson's trichrome staining and analyzed for lung fibrosis. Results: Twenty-four hours after the LPS exposure, the number of total cells and neutrophils in the BALF was increased. In the group receiving febuxostat, the number of total cells and neutrophils were significantly decreased at 24 hours after the LPS exposure. At 7 days after the LPS exposure, the number of total cells and neutrophils in both LPS and LPS + Febuxostat group returned to almost the same level as control group. Additionally, the percentage of collagen deposition area representing lung fibrosis in the entire lung field was enhanced in LPS group compared to control group at 7 days after the LPS exposure. Moreover, the treatment of febuxostat inhibited the fibrosis in LPS group. Conclusions: Administration of febuxostat inhibited the lung inflammation in the acute phase and improved the lung fibrosis in LPS-induced lung injury model. This study suggests that the treatment of febuxostat may inhibit the lung injury caused in severe COVID-19 patients.