The Protective Effect of Sodium Ferulate and Oxymatrine Combination on Paraquat-induced Lung Injury

Abstract

Experimental evidence suggested that sodium ferulate (SF) and oxymatrine (OMT) combination had synergistic anti-inflammatory and antioxidant effects. We hypothesized that SF and OMT combination treatment might have protective effects on paraquat-induced acute lung injury. In our study, the Swiss mice were randomly divided into seven groups, including control, paraquat (PQ), SF (6.2 mg/Kg/day); OMT (13.8 mg/Kg/day) and three SF+OMT groups (3.1 + 6.9; 6.2 + 13.8 and 12.3 + 27.7 mg/Kg/day). The mortality and death time were monitored. Sprague-Dawley rats were randomly divided into seven groups including control, PQ, SF (3.1 mg/Kg/day); OMT (6.9 mg/Kg/day) and three SF+OMT groups (1.6 + 3.4; 3.1 + 6.9 and 6.2 + 13.8 mg/Kg/day). The lung wet/dry weight (W/D) ratio, lung histopathologic changes, C-reactive protein (CRP), interleukin-6 (IL-6), nuclear factor κB (NF-κB), malondialdehyde (MDA) and superoxidase dismutase (SOD) were analysed. Compared with PQ group, the mortality significantly decreased and the death time prolonged in SF and OMT combination treatment groups of mice. Also in SF and OMT combination treatment groups of rats, the increased lung W/D ratio and histopathological score induced by PQ injection were significantly decreased; the levels of CRP, IL-6, NF-κB and MDA in serum and lung homogenate were significantly decreased; the SOD activities in serum and lung homogenate were improved. These results suggested that SF and OMT combination had an obvious protective effect on PQ-induced lung injury. The anti-inflammatory and antioxidant effect might be involved in the mechanism.

Keywords: Inflammation; Lung; Oxymatrine; Paraquat; Sodium ferulate.

Figure 1

Effects of SF and OMT combination on the death time of PQ-intoxication mice. CON, PQ, SF and OMT represent the control group, paraquat group, sodium ferulate group (6.2 mg/Kg/day) and oxymatrine group (13.8 mg/Kg/day), respectively. SF+OMT represents sodium ferulate and oxymatrine combination treatment groups, and the 3.1 + 6.9, 6.2 + 13.8 and 12.3 + 27.7 respectively represent drug administration doses of SF+OMT in the low dose group, middle dose group and high dose group. Data are expressed as means ± SEM. n = 10 in each group. ^##P < 0.01 compared with the control group. ^*P < 0.05, **P < 0.01 compared with the PQ group

Figure 2

Effects of SF and OMT combination on the lung Wet/Dry (W/D) ratio of PQ intoxication rats. CON, PQ, SF and OMT represent the control group, paraquat group, sodium ferulate group (3.1 mg/Kg/day) and oxymatrine group (6.9 mg/Kg/day), respectively. SF+OMT represents sodium ferulate and oxymatrine combination treatment groups, and the 1.6 + 3.4, 3.1 + 6.9 and 6.2 + 13.8 respectively represent drug administration doses of SF+OMT in the low dose group, middle dose group and high dose group. The lung W/D ratio was determined at 56 h after the PQ injection. Data are expressed as means ± SEM. n = 10 in each group. ^##P < 0.01 compared with the control group. ^*P < 0.05, **P < 0.01 compared with the PQ group

Figure 3

Effects of SF and OMT combination on the lung histopathological changes of PQ-intoxication rats. CON, PQ, SF and OMT represent the control group, paraquat group, sodium ferulate group (3.1 mg/Kg/day) and oxymatrine group (6.9 mg/Kg day), respectively. SF+OMT represents sodium ferulate and oxymatrine combination treatment groups, and the 1.6 + 3.4, 3.1 + 6.9 and 6.2 + 13.8 respectively represent drug administration doses of SF+OMT in the low dose group, middle dose group and high dose group. The degree of lung injury was scored under light microscopy from 0–4 as follow: 0 (no damage), 1 (slight diffuse damage of neutrophilic in alveolar walls, no thickening of alveolar walls, no hemorrhage, < 25 % congestion of alveolar space); 2 (diffuse damage of mononuclear and neutrophilic in alveolar walls and slight thickening of the alveolar walls, at least five erythrocytes per alveolus in one to five alveoli, < 25-30 % congestion of alveolar space,); 3 (two or three times thickening of the alveolar walls, at least five erythrocytes in five to ten alveoli, 30-50% congestion of alveolar space); 4 (alveolar wall thickening with up to 50% of lung consolidated, at least five erythrocytes in more than ten alveoli, > 60 % congestion of alveolar space). Data are expressed as means ± SEM. n = 10 in each group. ^##P < 0.01 compared with the control group. *P < 0.05, **P < 0.01 compared with the PQ group.

Figure 4

Effects of SF and OMT combination on the levels of CRP (a), IL-6 (b), NF-κB (c) in the serum of the PQ-intoxication rats. CON, PQ, SF and OMT represent the control group, paraquat group, sodium ferulate group (3.1 mg/Kg/day) and oxymatrine group (6.9 mg/Kg/day), respectively. SF+OMT represents sodium ferulate and oxymatrine combination treatment groups, and the 1.6 + 3.4, 3.1 + 6.9 and 6.2 + 13.8 respectively represent drug administration doses of SF+OMT in the low dose group, middle dose group and high dose group. Data are expressed as means ± SEM, n = 10 in each group. ^##P < 0.01 compared with the control group. ^*P < 0.05, **P < 0.01 compared with the PQ group.

Figure 5

Effects of SF and OMT combination on the levels of CRP (a), IL-6 (b), NF-κB (c) in the lung homogenate of the PQ-intoxication rats. CON, PQ, SF and OMT represent the control group, paraquat group, sodium ferulate group (3.1 mg/Kg/day) and oxymatrine group (6.9 mg/Kg/day), respectively. SF+OMT represents sodium ferulate and oxymatrine combination treatment groups, and the 1.6 + 3.4, 3.1 + 6.9 and 6.2 + 13.8 respectively represent drug administration doses of SF + OMT in the low dose group, middle dose group and high dose group. Data are expressed as means ± SEM, n = 10 in each group. ^##P < 0.01 compared with the control group. ^*P < 0.05, **P < 0.01 compared with the PQ group.

Figure 6

Effects of SF and OMT combination on MDA levels and SOD activities of the PQ-intoxication rats. a: MDA levels in the serum; b: MDA levels in the lung homogenate; c: SOD activities in the serum; d: SOD activities in the lung homogenate. CON, PQ, SF and OMT represent the control group, paraquat group, sodium ferulate group (3.1 mg/Kg/day) and oxymatrine group (6.9 mg/Kg/day), respectively. SF+OMT represents sodium ferulate and oxymatrine combination treatment groups, and the 1.6 + 3.4, 3.1 + 6.9 and 6.2 + 13.8 respectively represent drug administration doses of SF+OMT in the low dose group, middle dose group and high dose group. Data are expressed as means ± SEM. n = 10 in each group. ^##P < 0.01 compared with the control group. ^*P < 0.05, **P < 0.01 compared with the PQ group.