Dimethyl fumarate attenuates paraquat-induced pulmonary oxidative stress, inflammation and fibrosis in mice

Abstract

Paraquat (PQ) is the most important cationic bipyridyl herbicide in the agricultural industry, which is very toxic to humans and animals and causes disruption in many organs, mainly in the lungs. Dimethyl fumarate (DMF) is an immune-modulating drug used in the treatment of multiple sclerosis and psoriasis shows antioxidant, anti-inflammatory, and antifibrotic effects. In this study, the ameliorative effects of DMF (10, 30 and 100 mg/kg, orally) on PQ (30 mg/kg) model of lung damage were evaluated in male mice. DMF was given daily for 7 days and PQ was administrated in the fourth day in a single dose. On the eighth day, the animals were sacrificed, and their lung tissue were removed. The results indicated that DMF can ameliorate PQ-induced the significant increase in lung index, hydroxyproline, as well as TBARS, TGF-β, NF-κB and decrease in the amount of total thiol, catalase, glutathione peroxidase, superoxide dismutase, Nrf-2, and INF-γ. The histopathological results confirmed indicated findings. The results showed that the protective effect of DMF on PQ-induced toxicity is mediated through antioxidant, anti-inflammatory and antifibrotic activities.