Febuxostat, an inhibitor of xanthine oxidase, ameliorates ionizing radiation-induced lung injury by suppressing caspase-3, oxidative stress and NF-κB

Abstract

Febuxostat (FBX), a selective inhibitor of xanthine oxidase, has several biological properties such as antioxidant, anti-inflammatory and anti-apoptosis activities. The purpose of this study was to evaluate the protective effect of FBX against ionizing radiation (IR)-induced lung injury through mitigation of oxidative stress, inflammation and apoptosis. Sixty-four mice were randomized into eight groups as control, FBX (5, 10, and 15 mg/kg), IR (6 Gy), and IR + FBX (IR + FBX in three doses). Mice were received FBX for 8 consecutive days and then were exposed to IR at a single dose (6 Gy) of X-ray. At 1 and 7 days after irradiation, the biochemical parameters were analyzed in lung tissue, while histological and immunohistochemical examinations were evaluated 1 week after irradiation. Irradiation led to elevate of oxidative stress parameters (an increase of MDA, PC, NO, and decrease of GSH), inflammation and apoptosis in lung of mice. Furthermore, IR resulted in histopathological changes in the lung tissues. These changes were significantly mitigated by FBX treatment. FBX also inhibited immunoreactivity of caspase-3, NF-κB, and reduced oxidative stress. This study showed that FBX is able to protect lung injury induced by IR through inhibiting apoptosis (caspase-3), oxidative stress and inflammation (NF-κB).

Keywords:

• Febuxostat
• radioprotective
• ionizing radiation
• oxidative stress
• caspase-3
• NF-κB

Author contributions

S. J. H. designed this study. M. R., F. T. A, S. F., A. G., and S. J. H. contributed to experiments. S. J. H. designed and wrote the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by a grant from Mazandaran University of Medical Sciences, Sari, Iran [ID # 3353]. Seyed Jalal Hosseinimehr was received this grant. This study was the subject of a Pharm D. thesis of Marziyeh Raeispour as a student of Mazandaran University of Medical Sciences, Sari, Iran.