Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats.
Vitamin A (VA) kinetics was studied in rats with marginal VA stores before, during, and after inflammation. Rats received orally [11,12-(3)H(N)]retinol ([(3)H]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 [(3)H]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 x 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.
Gieng
Sin H
SH
Children's Hospital Oakland Research Institute, Oakland, CA, USA.
Green
Michael H
MH
Green
Joanne B
JB
Rosales
Francisco J
FJ
D000818:Animals; D001692:Biological Transport; D001769:Blood; D002451:Cell Compartmentation; D003198:Computer Simulation; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007668:Kidney; D008099:Liver / Q000737:chemistry*; D008954:Models, Biological; D010599:Pharmacokinetics; D051381:Rats; D014316:Tritium / Q000493:pharmacokinetics; D014801:Vitamin A / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*
D014316:Tritium; D014801:Vitamin A