Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats
Journal of Lipid Research
hyporetinoelmia, kinetic analysis, retinol, Windows version of Simulation, Analysis, Modeling Software
Food Science | Nutrition
Vitamin A (VA) kinetics was studied in rats with marginal VA stores before, during, and after inflammation. Rats received orally [11,12-3H(N)]retinol ([3H]VA; day 0), and inflammation was induced on day 21 with lipopolysacchride (LPS) for 3 days (n = 5) or recombinant human interleukin-6 (rhIL-6) for 7 days (n = 5). Both the fraction of [3H]VA and retinol concentrations in plasma were reduced significantly by LPS or rhIL-6. Compartmental analysis using the Windows version of Simulation, Analysis, and Modeling software was applied to group mean data, and non-steady-state models were developed. After absorption, VA kinetics was described by a three-compartment model that included plasma, kidney/interstitium, and liver/carcass. Four mechanisms decreasing plasma retinol were investigated: increased urinary excretion, increased irreversible loss, increased movement into interstitium, and decreased hepatic mobilization. Modeling demonstrated that a 79% reduction in hepatic mobilization of retinol (from 4.3 to 0.9 nmol/h) by 15 h after LPS best accounted for the observed changes in plasma VA kinetics (sum of squares = 9.05 × 10−07). rhIL-6 caused an earlier reduction (75% by 5.6 h). These models predicted a return to control values by 10 days after inflammation. If prolonged, inflammation-induced hyporetinolemia can render hepatic retinol unavailable to extrahepatic tissues, possibly leading to their impaired function, as observed in VA-deficient children with measles infection.
Sin Gieng, Michael Green, Joanne Green, and Francisco Rosales. "Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats" Journal of Lipid Research (2007): 904-913. https://doi.org/10.1194/jlr.M600528-JLR200
This research was originally published in Journal of Lipid Research. Sin H. Gieng, Michael H. Green, Joanne B. Green, and Francisco J. Rosales. Details for Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats. Journal of Lipid Research. 2007; 48:904-913. © The American Society for Biochemistry and Molecular Biology.
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