All-trans-retinoic acid distribution and metabolism in vitamin A-marginal rats

Christopher J. Cifelli, A. Catharine Ross

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Retinoids, including all-trans-retinoic acid (RA), are considered to have anti-inflammatory properties and are used therapeutically for diseases of the skin and certain cancers. However, few studies have addressed the effects of disease states on RA metabolism. The present study was conducted to better understand the effects of exogenous RA, both in the absence and presence of inflammation, on the distribution and metabolism of a dose of [3H]RA. Female Sprague-Dawley rats fed a low vitamin A diet were pretreated with RA (po), a low dose of lipopolysaccharide (LPS, ip), or their combination. Twelve hours later, albumin-bound [3H]RA was injected intravenously, and tissue organic- and aqueousphase 3H was determined after 10 and 30 min. In liver and plasma, 3H-labeled organic metabolites (e.g., 4-oxo- and 4-hydroxy-RA) were isolated by solid-phase extraction. LPS-induced inflammation significantly reduced plasma retinol by 47%, increased total 3H in plasma at 10 min, and reduced total 3H in liver at both times. In contrast, RA pretreatment did not affect plasma retinol, significantly increased total 3H in plasma at both times, and did not affect liver total 3H. However, by 30 min, RA significantly increased [3H]RA metabolism in plasma, liver, lung, and small intestine, as indicated by greater 3H-labeled aqueous-phase and 3H-labeled organic-phase metabolites. The results presented here demonstrate that, although LPS-induced inflammation affects the organ distribution of RA, the ability of RA to induce its own catabolism is maintained during inflammation. Thus we conclude that RA and LPS act independently to alter RA metabolism in vitamin A-marginal rats.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume291
Issue number2
DOIs
StatePublished - Jul 14 2006

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Tretinoin
Vitamin A
Inflammation
Liver
Hydroxy Acids
Solid Phase Extraction
Retinoids
Skin Neoplasms
Small Intestine
Sprague Dawley Rats
Lipopolysaccharides
Albumins
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

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title = "All-trans-retinoic acid distribution and metabolism in vitamin A-marginal rats",
abstract = "Retinoids, including all-trans-retinoic acid (RA), are considered to have anti-inflammatory properties and are used therapeutically for diseases of the skin and certain cancers. However, few studies have addressed the effects of disease states on RA metabolism. The present study was conducted to better understand the effects of exogenous RA, both in the absence and presence of inflammation, on the distribution and metabolism of a dose of [3H]RA. Female Sprague-Dawley rats fed a low vitamin A diet were pretreated with RA (po), a low dose of lipopolysaccharide (LPS, ip), or their combination. Twelve hours later, albumin-bound [3H]RA was injected intravenously, and tissue organic- and aqueousphase 3H was determined after 10 and 30 min. In liver and plasma, 3H-labeled organic metabolites (e.g., 4-oxo- and 4-hydroxy-RA) were isolated by solid-phase extraction. LPS-induced inflammation significantly reduced plasma retinol by 47{\%}, increased total 3H in plasma at 10 min, and reduced total 3H in liver at both times. In contrast, RA pretreatment did not affect plasma retinol, significantly increased total 3H in plasma at both times, and did not affect liver total 3H. However, by 30 min, RA significantly increased [3H]RA metabolism in plasma, liver, lung, and small intestine, as indicated by greater 3H-labeled aqueous-phase and 3H-labeled organic-phase metabolites. The results presented here demonstrate that, although LPS-induced inflammation affects the organ distribution of RA, the ability of RA to induce its own catabolism is maintained during inflammation. Thus we conclude that RA and LPS act independently to alter RA metabolism in vitamin A-marginal rats.",
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All-trans-retinoic acid distribution and metabolism in vitamin A-marginal rats. / Cifelli, Christopher J.; Ross, A. Catharine.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 291, No. 2, 14.07.2006.

Research output: Contribution to journalArticle

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AU - Ross, A. Catharine

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