Effects of edaravone, a free radical scavenger, on bleomycin-induced lung injury in mice

¹ Division of Pulmonary Medicine, Dept of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan; and Division of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
² Division of Pulmonary Medicine, Dept of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
³ Division of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan

^* To whom correspondence should be addressed. E-mail: tajimash{at}med.niigata-u.ac.jp.

	Abstract

Reactive oxygen species (ROS) play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. We hypothesized that edaravone, a free radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress.

Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg·kg^-1 of BLM. Edaravone (300 mg·kg^-1) was given by intraperitoneal administration at 1 h before BLM challenge.

Edaravone significantly improved the survival rate of mice treated with BLM from 25% to 90% (p=0.002), reduced the number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) on Day 7 (p<0.05), and attenuated the concentrations of lipid hydroperoxide (LPO) in BALF and serum on Day 2 (p<0.05). The fibrotic change in the lung on Day 28 was ameliorated by edaravone, as evaluated by histologic examination and measurement of hydroxyproline contents (p<0.05). In addition, edaravone significantly increased the prostaglandin E₂ (PGE₂) concentration in BALF on Day 2 (p=0.043).

In summary, edaravone was shown to inhibit lung injury and fibrosis via the repression of LPO production and the elevation of PGE₂ production in this experimental murine system.