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Increased epithelial apoptosis and decreased oxidant injury in silymarin-treated rats with sepsis-induced acute lung injury

Introduction

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.

Methods

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.

Results

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).

Conclusion

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.

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Canikli, S., Bayraktar, N., Turkoglu, S. et al. Increased epithelial apoptosis and decreased oxidant injury in silymarin-treated rats with sepsis-induced acute lung injury. Crit Care 13, P336 (2009). https://doi.org/10.1186/cc7500

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Keywords

  • Pulmonary Edema
  • Acute Lung Injury
  • Malondialdehyde
  • Silymarin
  • Glutathione Level