Increased epithelial apoptosis and decreased oxidant injury in silymarin-treated rats with sepsis-induced acute lung injury
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KeywordsPulmonary Edema Acute Lung Injury Malondialdehyde Silymarin Glutathione Level
Studies have demonstrated that silymarin (milk thistle) has cytoprotective effects and induces apoptosis. We hypothesized that silymarin decreases sepsis-induced acute lung injury (ALI) in a cecal ligation and puncture (CLP) rat model through its anti-inflammatory and antioxidant effects.
Forty-eight rats were randomized to sham (n = 16), control (n = 16), and silymarin (n = 16) groups. ALI was induced with CLP in the control and silymarin groups. Animals in the silymarin group received silymarin 50 mg/kg/day for 3 days before the experiment and 2 days afterward. Serum and bronchoalveolar lavage fluid TNFα, IL-1β, and IL-6; lung tissue malondialdehyde and glutathione 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. Apoptosis was quantitated using paraffin sections of lung by fluorescent terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling. Survival analyses were also performed.
Mortality rates for the silymarin and control groups were 37.5% and 87.5%, respectively (log-rank P = 0.0503). Compared with the silymarin group, the control group exhibited significantly more severe lung injury, as indicated by higher mean values for serum and bronchoalveolar lavage fluid TNFα (P = 0.01 for both), IL-1β (P ≤ 0.028 for both), and IL-6 (P ≤ 0.01 for both); neutrophil infiltration of the lungs (P = 0.003); pulmonary edema (P = 0.001); total lung histopathologic injury score (P < 0.001); w/d (P = 0.019); and lung-tissue malondialdehyde (P = 0.011) levels. Lung tissue glutathione levels were significantly higher in the silymarin group than the control group (P = 0.001). Compared with the control group, induction of apoptosis was increased in the silymarin group (P = 0.003).
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 the inflammatory process and oxidative injury and its proapoptotic effect.
This article is published under license to BioMed Central Ltd.