Surfactant and Varespladib Co-Administration in Stimulated Rat Alveolar Macrophages Culture.

Surfactant and Varespladib Co-Administration in Stimulated Rat Alveolar Macrophages Culture.
Curr Pharm Biotechnol. 2013 Apr 12;
Authors: De Luca D, Vendittelli F, Trias J, Fraser H, Minucci A, Gentile L, Perez-Gil J, Conti G, Antonelli M, Capoluongo ED
Abstract
Acute lung injury is a life-threating condition characterized by surfactant dysfunction and raised secretory phospholipase A2 (sPLA2) activity. Varespladib is a sPLA2 inhibitor shown to be effective in animal models of acute lung injury. We aimed at investigating the effect of co-administration of surfactant and varespladib on sPLA2 activity. Alveolar macrophages were cultured and stimulated with lipopolysaccharide and then treated with either varespladib, surfactant, varespladib followed by surfactant or nothing. sPLA2 activity, free fatty acids, tumour necrosis factor-(TNF- ) and protein concentrations were measured in culture supernatants. Treatment with varespladib (p=0.019) and varespladib + surfactant (p=0.013), reduced the enzyme activity by approximately 15% from the basal level measured in the untreated cultures. Surfactant, varespladib and varespladib + surfactant, respectively decreased free fatty acids by -45% (p=0.045), -62% (p=0.009) and -48% (p=0.015), from the baseline concentration of the untreated cultures. Varespladib and poractant- co-administration reduces sPLA2 activity and free fatty acids release in cultured rat alveolar macrophages, although a clear drug synerg...

Source: Current Pharmaceutical Biotechnology - April 12, 2013 Category: Biotechnology Authors: De Luca D, Vendittelli F, Trias J, Fraser H, Minucci A, Gentile L, Perez-Gil J, Conti G, Antonelli M, Capoluongo ED Tags: Curr Pharm Biotechnol Source Type: research