Silymarin mitigates lung impairments in a rat model of acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a deadly disease and lacks effective treatments. Inflammation and oxidative stress play key roles in ARDS development. We aimed to evaluate the efficacy of pretreatment of silymarin, which has capacities of anti-inflammatory and anti-oxidative stress, in ARDS. We used lipopolysaccharide (LPS) to generate an ARDS rat model, which was pretreated with silymarin. Lung wet/dry ratio and broncho-alveolar lavage fluid (BALF) analyses were performed. Histological changes of the lungs were evaluated using hematoxylin and eosin staining. Cells and proteins in BALF were determined. Protein levels in the lungs were assessed using immunoblotting. LPS administration significantly caused an increased lung wet/dry ratio, an elevated protein level in BALF, and an impaired pulmonary function in the rats. Silymarin mitigated these changes in a dose-dependent manner. Silymarin ameliorated LPS-induced histological changes of the lungs, and reduced infiltration of lymphocytes, macrophages, and neutrophils. Consistently, concentrations of pro-inflammatory cytokines such as interferon-γ, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were increased, while that of anti-inflammatory cytokine IL-10 was decreased in BALF. Additionally, silymarin pretreatment partially inactivated multiple mitogen-activated protein kinase signaling pathways in the lungs. Silymarin mitigated LPS-induced lung impairments by down-regulating inflammation in a rat model.