Anti-oxidant effect of pirfenidone on acute lung injury induced by paraquat poisoning in mice
10.3760/cma.j.issn.2095-4352.2016.10.008
- VernacularTitle:吡啡尼酮对百草枯中毒致急性肺损伤 小鼠的抗氧化作用
- Author:
Wei LI
;
Wenjie TANG
;
Zongfeng HU
;
Changsheng XU
;
Wen'ge LIU
;
Yingzi HUANG
;
- Publication Type:Journal Article
- Keywords:
Paraquat;
Acute poisoning;
Pirfenidone;
Acute lung injury;
Anti-oxidant
- From:
Chinese Critical Care Medicine
2016;28(10):901-905
- CountryChina
- Language:Chinese
-
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), and lasted to 72 hours (pg/mg: 110.47±5.91 vs. 82.70±2.79, P < 0.05); the activity of SOD was significantly enhanced in early stage (2-6 hours; U/mg: 39.34±1.17 vs. 34.72±1.54 at 2 hours, 37.37±0.90 vs. 33.75±0.93 at 6 hours, both P < 0.05) followed by a gradual decrease; the content of MDA within 24 hours was significantly increased (nmol/mg: 1.67±0.22 vs. 1.03±0.09 at 2 hours, 1.56±0.17 vs. 1.14±0.16 at 24 hours, both P < 0.05) followed by a gradual decrease. Compared with the PQ poisoned group, both high and low dose PD treatment could significantly inhibit NF-κB from 24 hours to 72 hours, and significantly inhibit MDA within 24 hours; high dose PD treatment could increase SOD activity at 6 hours, which showed a tendency of decreasing followed by increasing in low dose PD treatment group. Compared with high dose PD treatment group, the inhibition of MDA in low dose PD treatment group was more significant (nmol/mg: 0.90±0.08 vs. 1.29±0.18 at 2 hours, 1.03±0.32 vs. 1.84±0.43 at 6 hours, 1.08±0.09 vs. 1.33±0.16 at 24 hours, all P < 0.05), and SOD activity was significantly decreased at 6 hours (U/mg: 35.24±2.08 vs. 38.46±0.87, P < 0.05), and it was increased at 72 hours (U/mg: 39.81±1.30 vs. 34.58±3.15, but 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.
