Efeitos antioxidantes e anti-inflamatórios dos ésteres fumáricos no enfisema pulmonar

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is characterized by chronic lung inflammation and destruction of lung parenchyma (emphysema), with only symptomatic treatment available. Molecules with antioxidant and anti-inflammatory properties, such as dimethyl fumarate (DMF), have shown therapeutic potential. Currently, DMF has already been used clinically for the treatment of multiple sclerosis (MS) and psoriasis. This study evaluated the effects of DMF and its metabolite, monomethyl fumarate (MMF), on the activation of lung epithelial cells (PC9) induced by cigarette smoke (in vitro) and lung inflammation induced by porcine pancreatic elastase (EPP) in mice (in vivo). In vitro, PC-9 cells were treated with MMF at concentrations of 10, 30, and 100 μM and exposed to cigarette smoke extract (CFE 5%) to evaluate cell viability, oxidative stress (ROS), lipid peroxidation, and nitrite production. In vivo, C57BL/6 mice were treated with DMF (30 and 100 mg/kg) during (concomitant treatment) and after emphysema induction by EPP (recovery). ROS levels, total cell count in bronchoalveolar lavage (BAL), lung histology, and expression of oxidative stress proteins (SOD1, HO-1) were analyzed. MMF reduced oxidative stress and lipid peroxidation under in vitro conditions. In vivo, DMF reduced ROS levels (EPP 152.9 ± 18.64 vs CTRL 91.94 ± 8.998 / DMF30 85.45 ± 9.497 / DMF100 101.7 ± 27.49), inflammation, and prevented lung damage, such as an increase in mean alveolar diameter (Lm), which was reduced in the treated groups (PPE 51.40 ± 2.191 vs CTRL 30.50 / EPP30 42.80 ± 3.564 / EPP100 36.83 ± 2.714). SOD1 and HO-1 expression was modulated by DMF treatment. The results suggest that DMF may be an effective therapeutic alternative for COPD, reducing oxidative stress and inflammation.