Development of a Whole‐body Model of Vitamin A Metabolism in Neonatal Rats Treated with Oil or Vitamin A and Retinoic Acid (VARA) Based on Compartmental Analysis of Retinol Tracer Kinetics

Abstract

Compartmental modeling has contributed greatly to our understanding of vitamin A (VA) metabolism in adult animals and humans. However, VA metabolism in neonates is virtually uncharacterized. Our objectives were to compare VARA supplementation vs. placebo oil on whole‐body retinol kinetics and to develop a whole‐body model of VA metabolism in neonatal rats, taking into account the inherent metabolic non‐steady state of neonates. On post‐natal day 4, rat pups (n=3/time point) received an oral dose of 11,12‐[3H]retinol admixed with oil or VARA. In pups treated with oil, radioactivity in plasma retinol rose quickly between 1 and 6 hours, with the absorption peak at 6 hr. Then there was a rapid disappearance of tracer, followed by a leveling off which reflects the recycling of retinol between plasma and extravascular tissues and a flat slope from 2 d to 8 d. Then radioactivity further declined into a terminal slope, which represents the initiation of retinol degradation. In pups treated with VARA, peak fraction of the oral dose in plasma was lower. VARA was also associated with a more rapid accumulation of radioactivity in liver and an increased fraction of the oral dose in lung. A compartmental model as viewed from the “plasma space” indicated extensive recycling of retinol between plasma and tissues in neonates, as in adults. Also, VARA stimulated the turnover of retinol between plasma and extravascular tissues.NIH HD‐66982Grant Funding Source : NIH