Impaired phosphoglyceride metabolism in lung, spleen and thymus during lipopolysaccaride - induced acute respiratory distress syndrome in male wistar rats

Abstract

Acute lung injury (ALI) or its most severe form, acute respiratory distress syndrome (ARDS) is a clinically devastating and life threatening syndrome, which is caused mainly by dysfunctioning of pulmonary surfactants. Despite advances made in understanding the intricate molecular pathogenesis of ARDS for the past 3 decades, the mortality associated with ARDS still remains at ~ 40-50%. Lipopolysaccharide (LPS), is an endotoxin, a well known inducer compound for ALI/ARDS. In order to understand its pathogenic mechanism, alteration of phospholipid metabolism in pulmonary system in the current work is well studied. Previous reports have focussed mainly on phosphatidylcholine (PC), especially dipalmitoyl-PC (DPPC) and phosphatidylglycerol (PG) but the regulation of phospholipids in lungs during endotoxemia have not been elucidated. The immunological effect of LPS is also well documented in spleen and thymus; however impact on lipids particularly phospholipid metabolism is yet to be studied. Hence the present study was undertaken to investigate the role of phospholipids in lung, spleen and thymus during ARDS. Our objective was first initiated by in vitro metabolic labelling studies with [32P]orthophosphate followed by in vivo experiments. Labelling studies revealed significant impairments in PC and PG of lung, spleen and PC in thymus. The fatty acid (FA) analysis also showed marked alterations. To further understand the PL metabolism we have developed an animal model for ALI/ARDS [Sabarirajan et al., 2010]. Rats were divided into four groups. Group I, Control animals (24 h saline treated); Group II, III and IV were given LPS (10 mg/kg body wt.) intraperitoneally and sacrificed after 6, 12 and 24 h respectively. We observed reduced phospholipid content especially PC, PG in lung and major PL in spleen and thymus. FA distribution of individual PL shows an overall increase in unsaturated/saturated FA in lung, spleen and thymus. This might be due to the sensitive/adaptive response of the organ.