retinol-palmitate and Escherichia-coli-Infections

Retinols seem to be of clinical importance in ameliorating the clinical consequences of septic shock. These beneficial effects of retinols are suggested to be due to an antioxidant property. The present study was undertaken in order to confirm or rule out such an effect of retinol palmitate (RP) in experimental septic shock by measuring F2-isoprostanes and a major prostaglandin F2 alpha metabolite as indicators of oxidative injury and inflammatory response, respectively.. Fourteen anaesthetised pigs were randomly given an injection of RP (2.300 IU x kg-1) or the corresponding volume of vehicle. All pigs received a continuous infusion of E. coli endotoxin (10 micrograms x kg-1 x h-1). Blood samples were analysed for lipid peroxidation products (8-iso-PGF2 alpha), indicating free radical induced oxidative injury and 15-keto-dihydro-PGF2 alpha indicating cyclooxygenase-mediated inflammatory response).. Significantly elevated levels of 8-iso-PGF2 alpha were seen at 3, 5 and 6 hours of endotoxaemia in the vehicle + endotoxin group as compared to RP + endotoxin group. Endotoxin induced cyclooxygenase-mediated inflammatory response was not affected by RP.. This study is the first one to show that RP counteracts oxidative injury rather than inflammatory response in experimental septic shock. These results may be of importance for the understanding of some beneficial effects of RP during endotoxaemia (i.e. improved systemic haemodynamics and reduced serum levels of endotoxin). Our results may explain the therapeutic effects of nutrients rich in caroten/retinols used in some clinical studies.

Topics: Analysis of Variance; Animals; Antioxidants; Dinoprost; Disease Models, Animal; Diterpenes; Endotoxins; Escherichia coli Infections; F2-Isoprostanes; Female; Inflammation; Lipid Peroxidation; Male; Oxidative Stress; Radioimmunoassay; Random Allocation; Retinyl Esters; Shock, Septic; Swine; Vitamin A

Vitamin A reduces the pathophysiological effects of endotoxin in animals, but the mechanism and the lowest effective dose are not clear.. An intravenous bolus of endotoxin 20 microg. kg(-1) was given to 30 rabbits. In 10 of them, 1000 IE. kg(-1) retinyl palmitate was injected intravenously 1 h before the endotoxin and in another 10 rabbits 1 h after the endotoxin. A one-compartment open model was fitted to the time-concentration profile of endotoxin in plasma.. The half-life of endotoxin was half as long when vitamin A was given for prophylaxis (median 35 min) and for treatment (33 min) than in the controls (67 min; p < 0.004). The plasma concentrations of immunoglobulin G and M endotoxin-core antibodies, the leucocyte count and the acid-base balance did not differ between the groups during the experiment, but the pyrogenic reaction was more pronounced in the controls.. A fairly low dose of vitamin A reduced the half-life of endotoxin.

Topics: Analysis of Variance; Animals; Antibodies, Bacterial; Bacteremia; Disease Models, Animal; Diterpenes; Drug Evaluation, Preclinical; Endotoxins; Escherichia coli; Escherichia coli Infections; Immunoglobulin G; Immunoglobulin M; Injections, Intravenous; Leukocyte Count; Metabolic Clearance Rate; Nonlinear Dynamics; Rabbits; Random Allocation; Regression Analysis; Retinyl Esters; Time Factors; Vitamin A