A rat model of acute respiratory distress silymarin's antiinflamatory and antioxidant effect

Silymarin recently has been investigated for use as a cytoprotectant, an anticarcinogen, and a supportive treatment for liver damage from Amanita phalloides poisoning. Silymarin, a polyphenolic flavonoid antioxidant, is known to have anti-inflammatory, hepatoprotective, and anticarcinogenic effects. Hypothesis: Silymarin decreases sepsis induced acute lung injury (ALI) in a cecal ligation and puncture (CLP) rat model through its antiinflammatory and antioxidant effects. Methods: Forty-eight rats were randomized to sham (n=16), control (n=16), silymarin (n=14) groups. ALI was induced with CLP in control and silymarin groups. Animals in silymarin group received silymarin 50 mg/kg/day for 3 days before the experiment and 2 days afterward. Serum and bronchoalveolar lavage fluid (BALF) tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6; lung tissue malondialdehyde (MDA) and glutathione (GSH) levels; lung histopathologic examination; and lung wet-to-dry (w/d) weight ratio measurements were used to compare and evaluate the severity of lung injury between the groups. Survival analyses were also done. Results: Mortality rates for silymarin and control groups were 37.5% and 87.5%, respectively (log-rank P=0.0506). Compared with the silymarin group, the control group exhibited significantly more severe lung injury, as indicated by higher mean values for serum and BALF TNF-alpha, IL-1beta and IL-6 (P<0.05 for all measurments); neutrophil infiltration of the lungs (P=0.003); pulmonary edema (P=.001); total lung histopathologic injury score (P=0.001); w/d (P=0.019); and lung-tissue MDA (P=0.011) levels. Lung tissue GSH levels were significantly higher in silymarin group than control group (P=0.001). Conclusions : Silymarin reduces the severity of sepsis induced-ALI and may also improve survival in a CLP rat model. These beneficial effects of this agent are probably due to its inhibitory effects on inflammatory process and oxidative injury.