Vitamin A (retinol) status in the Gunn rat
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Abstract
- 1)
Data from vitamin A analyses demonstrate that the amount of vitamin A stored in the liver of untreated Gunn rats is of the same magnitude as that of Sprague-Dawley rats.
- 2)
The retinol content in the liver of both GG and GW rats was reduced to about 50% by TCDD-treatment.
- 3)
Retinol levels in serum were found to be variable and no significant effect due to TCDD could be observed.
- 4)
No correlation between the TCDD-induced reduction of vitamin A and the induction of UDPGT activity by TCDD could be demonstrated in this study. The vitamin A reduction caused by TCDD was considerably less in the Gunn rat than in the Sprague-Dawley rat, and the results indicate that the Gunn rat is more resistant to TCDD than other strains of rat. TCDD-induced reduction of liver vitamin A seems to some extent to correlate with TCDD-toxicity in different strains of rat. The specific properties of the Gunn rat and its relatively high resistance to TCDD make it a valuable tool in studies about the mechanism of TCDD-toxicity.
Key words
Vitamin A Retinol Gunn rat UDP-Glucuronosyltransferase Liver Serum 2,3,7,8-Tetrachlorodibenzo-p-dioxin TCDD High performance liquid chromatographyPreview
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References
- Abrams LS, Elliott HW (1974) Morphine metabolism in vivo and in vitro by homozygous Gunn rats. J Pharmacol Exp Ther 189: 285–292Google Scholar
- Aitio A (1973) Glucuronide synthesis in the rat and guinea pig lung. Xenobiotica 3: 13–22Google Scholar
- Aitio A, Parkki MG, Marniemi J (1979) Different effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on glucuronide conjugation of various aglycones. Studies in Wistar and Gunn rats. Toxicol Appl Pharmacol 47: 55–60Google Scholar
- Aitio A, Vainio H (1976) UDP-glucuronosyltransferase and mixed function oxidase activity in microsomes prepared by differential centrifugation and calcium aggregation. Acta Pharmacol Toxicol 39: 555–561Google Scholar
- Arias IM (1959) A defect in microsomal function in non-hemolytic acholuric jaundice. J Histochem Cytochem 7: 250–252Google Scholar
- Arias IM (1961) Ethereal and N-linked glucuronide formation by normal and Gunn rats in vitro and in vivo. Biochem Biophys Res Commun 6: 81–84Google Scholar
- Arias IM, Furman M, Tapley DF, Ross JE (1963) Glucuronide formation and transport of various compounds by Gunn rat intestine in vitro. Nature 197: 1109–1110Google Scholar
- Bock KW, Clausbruch UCV, Ottenwälder H (1978) UDP-glucuronyltransferase in perfused rat liver and in microsomes: V. Studies with Gunn rats. Biochem Pharmacol 27: 369–371Google Scholar
- Carbone JV, Grodsky GM (1957) Constitutional non-hemolytic hyperbilirubinemia in the rat: Defect of bilirubin conjugation. Proc Soc Exp Biol Med 94: 461–463Google Scholar
- Dunagin PE Jr, Zachman RD, Olson JA (1964) Identification of free and conjugated retinoic acid as a product of retinal (vitamin A aldehyde) metabolism in the rat in vivo. Biochim Biophys Acta 90: 432–434Google Scholar
- Dunagin PE Jr, Meadows EH Jr, Olson JA (1965) Retinoyl beta-glucuronic acid: a major metabolite of vitamin A in rat bile. Science 148: 86–87Google Scholar
- Dunagin PE Jr, Zachman RD, Olson JA (1966) The identification of metabolites of retinal and retinoic acid in rat bile. Biochim Biophys Acta 124: 71–85Google Scholar
- Goodman DS (1980) Vitamin A metabolism. Fed Proc 39: 2716–2722Google Scholar
- Gunn CH (1938) Hereditary acholuric jaundice in a new mutant strain of rats. J Hered 29: 137–139Google Scholar
- Göthe R, Leander K, Palmer L, Thunberg T (1978) Synthesis of (2,3,7,8-37Cl)-tetrachloro(1,4,6,9-2H)dibenzo-p-dioxin and its use as an internal standard in quantitations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by mass fragmentography. Acta Pharmaceutica Suecica 15: 321–326Google Scholar
- Isselbacher KJ (1956) Enzymatic mechanism of hormone metabolism II. Mechanism of hormonal glucuronide formation. In: Pincus G (ed) Recent Progress in Hormone Research. Academic Press, New York, pp 134–151Google Scholar
- Jacobson MM, Levin W, Conney AH (1975) Studies on bilirubin and steroid glucuronidation by rat liver microsomes. Biochem Pharmacol 24: 655–662Google Scholar
- Lippel K, Olson JA (1968) Biosynthesis of beta-glucuronides of retinol and retinoic acid in vivo and in vitro. J Lipid Res 9: 168–175Google Scholar
- Lotan R (1980) Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta 605: 33–91Google Scholar
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275Google Scholar
- Miller GL (1959) Protein determination for large numbers of samples. Anal Chem 31: 964Google Scholar
- Neal RA, Beatty PW, Gasiewicz TA (1979) Studies of the mechanisms of toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Ann NY Acad Sci 320: 204–213Google Scholar
- Okulicz-Kozaryn I, Schaeffer M, Batt A-M, Siest G, Loppinet V (1981). Stereochemical heterogeneity of hepatic UDP-glucuronosyltransferase activity in rat liver microsomes. Biochem Pharmacol 30: 1457–1461Google Scholar
- Ong DE, Chytil F (1974) Multiple retinol binding proteins in rabbit lung. Biochem Biophys Res Commun 59: 221–229Google Scholar
- Ong DE, Chytil F (1978) Cellular retinol-binding protein from rat liver. J Biol Chem 253: 828–832Google Scholar
- Poland A, Glover E, Kende AS (1976) Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. J Biol Chem 251: 4936–4946Google Scholar
- Rappe C (1978) Decontamination of products formed during the industrial preparation of 2,4,5-trichlorophenol. In: Cattabeni F, Cavallaro A, Galli G (eds) Dioxin, toxicological and chemical aspects. Spectrum Publications, New York, pp 179–183Google Scholar
- Roberts AB, DeLuca HF (1967) Pathways of retinol and retinoic acid metabolism in the rat. Biochem J 102: 600–611Google Scholar
- Schmid R, Axelrod J, Hammaker L, Swarm RR (1958) Congenital jaundice in rats due to a defect in glucuronide formation. J Clin Invest 37: 1123–1130Google Scholar
- Stevenson I, Greenwood D, McEwen J (1968) Hepatic UDP-glucuronyltransferase in Wistar and Gunn rats — in vitro activation by diethylnitrosamine. Biochem Biophys Res Commun 32: 866–872Google Scholar
- Swanson BN, Frolik CA, Zaharevitz DW, Roller PP, Sporn MB (1981) Dose-dependent kinetics of all-trans-retinoic acid in rats. Plasma levels and excretion into bile, urine and faeces. Biochem Pharmacol 30: 107–113Google Scholar
- Takase S, Ong DE, Chytil F (1979) Cellular retinol-binding protein allows specific interaction of retinol with the nucleus in vitro. Proc Natl Acad Sci USA 76: 2204–2208Google Scholar
- Thunberg T, Ahlborg UG, Johnsson H (1979) Vitamin A (retinol) status in the rat after a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch Toxicol 42: 265–274Google Scholar
- Thunberg T, Ahlborg UG, Håkansson H, Krantz C, Monier M (1980) Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the hepatic storage of retinol in rats with different dietary supplies of vitamin A (retinol). Arch Toxicol 45: 273–285Google Scholar
- Uotila P, Parkki MG, Aitio A (1978) Quantitative and qualitative changes in the metabolism of benzo(a)pyrene in rat tissues after intragastric administration of TCDD. Toxicol Appl Pharmacol 46: 671–683Google Scholar
- Vainio H, Hietanen E (1974)a Drug metabolism in Gunn rats: inability to increase bilirubin glucuronidation by phenobarbital treatment. Biochem Pharmacol 23: 3405–3412Google Scholar
- Vainio H, Hietanen E (1974)b Induction deficiency of the microsomal UDP-glucuronosyltransferase by 3-methylcholanthrene in Gunn rats. Biochim Biophys Acta 362: 92–99Google Scholar
- Winsnes A, Dutton GJ (1973) Comparison between o-aminophenol glucuronidation in liver slices and homogenates from control and phenobarbital-treated Wistar and Gunn rats. Biochem Pharmacol 22: 1765–1771Google Scholar
- Wolf G (1980) Vitamin A. In: Alfin-Slater RB, Kritchevsky D (eds) Nutrition and the adult. Human Nutrition, a Comprehensive Treatise, vol 3 Part B. Plenum Press, New York, p 107Google Scholar
- Yeary RA, Grothaus RH (1971) The Gunn rat as an animal model in comparative medicine. Lab Animal Sci 21: 362–366Google Scholar
- Zakim D, Goldenberg J, Vessey DA (1973) Regulation of microsomal enzymes by phospholipids. VI. Abnormal enzyme-lipid interactions in liver microsomes from Gunn rats. Biochim Biophys Acta 297: 497–502Google Scholar
- Zile MH, Schnoes HK, DeLuca HF (1980) Characterization of retinoyl betaglucuronide as a minor metabolite of retinoic acid in bile. Proc Natl Acad Sci USA 77: 3230–3233Google Scholar