Therapeutic Role of Surfactant during Mitochondrial Membrane Mediated Apoptosis in Endotoxin Induced Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) induced by lipopolysaccharide (LPS) is known to be associated with pulmonary cytokine production resulting in infiltration of neutrophils and pulmonary injury. The study presented here is focused on the changes in cell death regulating proteins during lung injury and studied the relationship between the LPS challenged ARDS and the subsequent role of surfactant therapy against ARDS. Apoptotic features, such as induction of DNA fragmentation ladders in lung tissue, expression of cytoplasmic proteins (Bcl-2, Bax), mitochondrial proteins (cytochrome c, Apaf-1) and activation of caspases were detected following LPS exposure. Instillation of the surfactant derived from the natural source as well as synthetic surfactant prevents LPS induced apoptosis. These results suggest that the mechanism of induction of apoptosis by LPS depends on mitochondrial dysfunction and the anti-apoptotic effects of surfactant treatment conferred protection in the rat model during lung injury mediated via suppression of mitochondrial intrinsic pathway.