2,3,7,8-Tetrachlorodibenzo-p-dioxin Increases Serum and Kidney Retinoic Acid Levels and Kidney Retinol Esterification in the Rat

• Published in: Toxicology and applied pharmacology 2000-12, Vol.169 (2), p.121-131
• Main Authors: Nilsson, C.B., Hoegberg, P., Trossvik, C., Azaïs-Bræsco, V., Blaner, W.S., Fex, G., Harrison, E.H., Nau, H., Schmidt, C.K., van Bennekum, A.M., Håkansson, H.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Body Weight - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Cytochrome P-450 CYP1A1 - metabolism; Dose-Response Relationship, Drug; Esters - metabolism; hepatocytes; In Vitro Techniques; kidney; Kidney - drug effects; Kidney - metabolism; lecithin:retinol acyl transferase; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Organ Size - drug effects; Polychlorinated Dibenzodioxins - pharmacology; rat; Rats; Rats, Sprague-Dawley; retinoic acid; retinol-binding protein; Retinol-Binding Proteins - metabolism; retinyl ester hydrolase; stellate cells; TCDD; Time Factors; Toxicology; Tretinoin - blood; Tretinoin - metabolism; Various organic compounds; vitamin A; Vitamin A - metabolism
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.2000.9059

Halogenatedorganic environmental contaminants such as dioxins are well-known to affect tissue levels of retinoids. To further investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on retinoid homeostasis, adult male Sprague–Dawley rats were killed 1–112 days after a single oral dose of 10 μg TCDD/kg body wt. Additional groups of rats were killed three days after a single oral dose of 0.1, 1, 10, or 100 μg TCDD/kg body wt. Serum and renal retinoic acid levels were measured, as were levels of serum retinol-binding protein (RBP) in liver, kidneys, and serum. Hepatic and renal formation as well as hepatic hydrolysis of retinyl esters were determined, together with hepatic and renal retinoid levels. In addition, one of the retinyl ester hydrolase (REH) activities was investigated in isolated hepatocytes and hepatic stellate cells from rats killed 7 days after a single oral dose of 10 μg TCDD/kg body wt. No increased hepatic REH activity that could explain the decreased hepatic retinyl ester levels following TCDD treatment was found. In the liver, TCDD increased protein levels, but not mRNA levels, of RBP. A causal relationship is suggested for the increased renal lecithin:retinol acyltransferase (LRAT) activity and increased renal retinyl ester levels in TCDD-treated rats. Importantly, TCDD was shown to substantially increase serum and renal levels of retinoic acid. The ability of TCDD to cause increased tissue retinoic acid levels suggests that TCDD may alter the transcription of retinoic acid-responsive genes.