Febuxostat inhibits inflammation and fibrosis in a murine model of LPS-induced lung injury

Abstract

Introduction: It is thought that one of the factors to induce lung injury in ARDS patients is decrease of ATP production caused by mitochondrial dysfunction. Febuxostat, a treatment for hyperuricemia, has been shown to improve mitochondrial dysfunction and enhances the production of ATP.

Aim and objectives: We aimed to investigate the effect of febuxostat in a murine model of LPS-induced lung injury.

Methods: To develop the LPS-induced lung injury model, C57BL/6 mice were exposed to 100 mg of lipopolysaccharide (LPS) intratracheally. From 2 days prior to LPS exposure, 100 mg of febuxostat was administered twice daily for 4 or 10 days. Twenty-four hours or 7 days after LPS exposure, bronchial lavage fluid (BALF) and lung tissue were collected.

Results: Twenty-four hours after LPS exposure, the number of total cells and neutrophils in BALF were significantly increased compared to the saline exposed control group. There was a significant decrease of total cells and neutronphils at 24 hours after LPS exposure in the febuxostat treated group compared to the non-treated group. For histological analysis, we examined the percentage of collagen deposition area, which represent lung fibrosis, in the entire lung field by using Masson’s trichrome staining. The lung fibrosis was significantly induced at 7days after LPS exposure compared to the control group. Whereas, the administration of febuxostat inhibited the lung fibrosis caused by LPS exposure.

Conclusions: The administration of febuxostat inhibited the lung inflammation in acute phase and the lung fibrosis in late phase in LPS-induced lung injury model. This study suggests that treatment with febuxostat may improve the lung injury caused by ARDS.