Mobilization of vitamin A stores in rats after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin: A kinetic analysis

Sean K. Kelley, Charlotte B. Nilsson, Michael Henry Green, Joanne Balmer Green, Helen Håkansson

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic environmental contaminant that prevents the normal accumulation of vitamin A in liver and causes increased excretion of vitamin A. To determine what alterations in vitamin A metabolism occur first in response to TCDD treatment, we administered TCDD (7.0 μg/kg b.w.) orally to rats that had received a nonperturbing (tracer) iv dose of [3H]vitamin A-labeled plasma (n = 3) or lymph (n = 3) 21 days earlier. Within a few days after TCDD administration, fraction of the injected radiolabel in plasma, which had been in a terminal slope when plotted on a semilog scale, increased and remained elevated until the experiment was terminated (day 42). At that time, liver vitamin A levels were 65% lower in TCDD-perturbed rats than in controls. Using model-based compartmental analysis and compartmental models developed previously for control rats (S. K. Kelley et al., 1998, Toxicol. Sci, 44:1- 13), we determined the minimal changes needed to account for the perturbation in plasma [3H] tracer responses after TCDD administration. We determined that the effects of TCDD could be explained by adjusting the value of one fractional transfer coefficient corresponding to the mobilization of vitamin A from large, slowly turning-over pools. We speculate that this change corresponds to an increased fractional rate of retinyl ester hydrolysis, and that it precedes the TCDD-associated increased irreversible utilization and excretion of vitamin A.

Original languageEnglish (US)
Pages (from-to)478-484
Number of pages7
JournalToxicological Sciences
Volume55
Issue number2
StatePublished - Jun 26 2000

All Science Journal Classification (ASJC) codes

  • Toxicology

Fingerprint Dive into the research topics of 'Mobilization of vitamin A stores in rats after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin: A kinetic analysis'. Together they form a unique fingerprint.

  • Cite this

    Kelley, S. K., Nilsson, C. B., Green, M. H., Green, J. B., & Håkansson, H. (2000). Mobilization of vitamin A stores in rats after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin: A kinetic analysis. Toxicological Sciences, 55(2), 478-484.