Impaired phosphatidylcholine biosynthesis and ascorbic acid depletion in lung during lipopolysaccharide-induced endotoxaemia in guinea pigs.
Injection of guinea pigs with a single dose of Escherichia coli lipopolysaccharide (3.2 mg/100 g) induces a reversible endotoxic shock that was evaluated by measuring plasma glucose levels and aspartate aminotransferase activity at 24 h after lipopolysaccharide injection. The hypoglycaemia and the increase in plasma aminotransferase activity observed, correlated with the alterations found during the recovery phase of endotoxic shock. When lipid peroxidation and some antioxidant systems were measured in lungs from treated animals, we only found differences in ascorbic acid content, that was decreased by 50%. Lipopolysaccharide treatment results in a depression of pulmonary phosphatidylcholine synthesis, that correlates with the surfactant deficiencies associated with respiratory illnesses in septic shock. Guinea pigs fed on a diet with a low content in ascorbic acid were more sensitive to endotoxin. In these animals we found no detectable levels of ascorbic acid in lung, whereas both vitamin E lung levels and pulmonary phosphatidylcholine synthesis were significantly decreased. Our results point out the significance of ascorbic acid in the protection against oxidative lung injury associated to endotoxaemia, and validate our shock model for further studies on the mechanisms of this pathological condition.
Benito
E
E
Department of Biochemistry and Molecular Biology, Faculty of Chemistry, Universidad Complutense, Madrid, Spain.
Bosch
M A
MA
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism* / Q000494:pharmacology; D019446:Endotoxemia / Q000378:metabolism / Q000503:physiopathology*; D004926:Escherichia coli; D006168:Guinea Pigs; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D008070:Lipopolysaccharides; D010713:Phosphatidylcholines; D014810:Vitamin E; D013482:Superoxide Dismutase; D001205:Ascorbic Acid