TY - JOUR
T1 - Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats
AU - Gieng, Sin H.
AU - Green, Michael H.
AU - Green, Joanne B.
AU - Rosales, Francisco J.
PY - 2007/4
Y1 - 2007/4
N2 - 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 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-steadystate 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.
AB - 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 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-steadystate 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.
UR - http://www.scopus.com/inward/record.url?scp=34147181560&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34147181560&partnerID=8YFLogxK
U2 - 10.1194/jlr.M600528-JLR200
DO - 10.1194/jlr.M600528-JLR200
M3 - Article
C2 - 17235116
AN - SCOPUS:34147181560
SN - 0022-2275
VL - 48
SP - 904
EP - 913
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 4
ER -