Anti-oxidant effect of pirfenidone on acute lung injury induced by paraquat poisoning in mice / 中华危重病急救医学

ABSTRACT

Objective To investigate the anti-oxidant effect of pirfenidone (PD) at different dosage on acute lung injury (ALI) induced by paraquat (PQ) poisoning in mice. Methods 144 ICR mice were randomly divided into four groups control group (n = 24), PQ poisoned group (n = 24), high and low doses PD treatment groups (n = 48). ALI induced by PQ poisoning model was reproduced by intraperitoneal injection of 25 mg/kg 20% PQ solution in mice, and the mice in control group was given equal volume of normal saline. Intragastric administration with 30 mg/kg and 70 mg/kg PD suspension [PD was dissolved in 0.4% sodium carboxymethyl cellulose sodium (CMC) solution] after PQ poisoning immediately for 3 days in high and low doses PD treatment groups respectively, while the same volume of 0.4% CMC solution was administrated in control group and PQ poisoned group. Then mice in each group were respectively sacrificed at 2, 6, 12, 24, 48 and 72 hours after PD exposure to harvest the lung tissue, nuclear factor-κB (NF-κB) was determined by enzyme linked immunosorbent assay (ELISA), superoxide dismutase (SOD) and malonaldehyde (MDA) were determined by colorimetry, and pulmonary pathological changes were observed with microscope after hematoxylin-ensin (HE) staining. Results Compared with the control group, NF-κB from 2 hours in PQ poisoned group was significantly increased (pg/mg 106.65±5.96 vs. 79.04±2.40, P 0.05), but no significant difference in NF-κB activity at all time points was found. Under light microscope, a wide range of red blood cells and serous effusion, alveolar septum fracture and pulmonary interstitial inflammatory cell infiltration were shown by pathologic examination in PQ poisoned group. The pathologic changes in high and low doses PD treatment groups were obviously less than those of PQ poisoned group, and no significant difference was found between the two doses groups. Conclusions The early therapeutic effect of PD may relate to the inhibition of NF-κB and reactive oxygen species, then reduce the inflammation of PQ poisoning. The treatment effectiveness of low dose PD seems better than high dose PD.