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Drug-metabolizing enzyme activities in the liver and intestine of rats exposed to DDT: effects of vitamin A status

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Abstract

One-half of a group (deficient group) of male Wistar rats which received a daily intake of 50 IU of vitamin A/kg of body weight, and one-half of a second group (normal group), which received 500 IU of the same substance, were treated by intragastric intubation with 40 mg of DDT/day/kg body weight. Rats were killed after 5 or 12 days of exposure to DDT. The liver vitamin A contents indicated a different rate of storage depending on the amount of vitamin A. DDT increased the relative liver weight and decreased hepatic vitamin A storage in both groups; it induced benzo(a)pyrene hydroxylase (AHH) and glutathione-S-transferase (GST) activities in both organs and cytochrome P 450 only in the liver. At both ages, no change was noted in the cytochrome P450 content in the liver and intestine, whereas enzymatic activities, unchanged in the liver, were significantly modified in the intestine and included a reduction in AHH activity, an increase in UDP-glucuronosyl transferase (UDPGT) and GST activities. Vitamin A deficiency had no effect on AHH and UDPGT activities nor on the cytochrome P 450 content in the liver or intestine. However, it significantly increased the GST activity in the intestine, but not in the liver.

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References

  • Bieri JG, McKenna MC (1981) Expressing dietary values for fat-soluble vitamins: Changes in concepts and terminology. Am J Clin Nutr 34:289–295

    Google Scholar 

  • Bock KW, Burchell B, Dutton GJ, Hanninen O, Mulder GJ, Owens IS, Siest G, Tephly TR (1983) UDP-giucuronosyltransferase activities. Guidelines for consistent interim terminology and assay conditions. Biochem Pharmacol 32:953–955

    Google Scholar 

  • Bonkovsky HL, Hauri HH, Marti U, Gasser R, Meyer UA (1985) Cytochrome P 450 of small intestinal epithelial cells. Immuno-chemical characterization of the increase in cytochrome P 450 caused by phenobarbital. Gastroenterology 88:458–467

    Google Scholar 

  • Borghoff SJ, Birnbaum LS (1985) Age-related changes in giucuronidation and deglucuronidation in liver, small intestine, lung and kidney of male Fischer rats. Drug Metab Dispos 13:62–67

    Google Scholar 

  • Campbell MA, Gyorkos J, Leece B, Homonko K, Safe S (1983) The effect of twenty-two organo-chlorine pesticides as inducers of the hepatic drug metabolizing. Gen Pharmacol 14:445–454

    Google Scholar 

  • Campbell TC, Hayes JR (1974) The role of nutrition in the drugmetabolizing enzyme systems. Pharmacol Rev 26:171–197

    Google Scholar 

  • Cappon ID, Nicholls DM (1974) Factors involved in increased protein synthesis in liver microsomes after administration of DDT. Pest Biochem Biophys 5:109–118

    Google Scholar 

  • Chhabra RS (1981) Effect of dietary factors and environmental chemicals on intestinal drug metabolizing enzymes. Toxicol Environ Chem 3:173–199

    Google Scholar 

  • Chhabra RS, Pohl RJ, Fouts JR (1974) A comparative study of xenobiotic metabolizing enzymes in liver and intestine of various animal species. Drug Metab Dispos 2:443–447

    Google Scholar 

  • Datta RR, Nelson MJ (1970) p,p′-DDT detoxication by isolated perfused rat liver and kidney. Ind Med Surg 39:195–198

    Google Scholar 

  • Deichmann WB, MacDonald WE (1971) Organochlorine pesticides and human health. Fd Cosmet Toxicol 9:91–103

    Google Scholar 

  • Dudeja PK, Mahmood A (1982) Effect of a single oral dose of p,p′-DDT on the absorption of nutrientsin vitro and on brush border enzymes in rat intestine. Arch Toxicol 49:131–138

    Google Scholar 

  • Duncan DB (1955) Multiple range and multiple F tests. Biometrics 11:1–42

    Google Scholar 

  • Gandemer G, Pascal G, Durand G (1979) Developmental changes in lipogenic enzyme activities in liver and adipose tissue of postweaning: Effect of sex and castration. Ann Biol Anim Biochem Biophys 19:573–581

    Google Scholar 

  • Habig WH, Pabst MJ, Jacoby WB (1974) Glutathione-S-transferases: The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    Google Scholar 

  • Hoffman DG, Worth HM, Emerson JL, Anderson RC (1970) Stimulation of hepatic drug-metabolizing enzymes by chlorophenothane (DDT): The relationship to liver enlargement and hepatotoxicity in the rat. Toxicol Appl Pharmacol 16:171–178

    Google Scholar 

  • Innami S, Nakamura A, Nagayama S (1974) Polychlorobiphenyl toxicity and nutrition: II. PCB toxicity and vitamin A. J Nutr Sci Vitaminol 20:363–370

    Google Scholar 

  • Leo MA, Lieber CS (1985) New pathway for retinol metabolism in liver microsomes. J Biol Chem 260:5228–5231

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin reagent. J Biol Chem 193:265–275

    Google Scholar 

  • Miranda CL, Muktar H, Bend JR, Chhabra RS (1979) Effects of vitamin A deficiency on hepatic and extrahepatic mixed-function oxidase and epoxide-metabolizing enzymes in guinea pig and rabbit. Biochem Pharmacol 28:2713–2716

    Google Scholar 

  • Morita A, Nakano K (1981) Change in vitamin A content in tissues of rats fed on a vitamin A-free-diet. J Nutr Sci Vitaminol 28:343–350

    Google Scholar 

  • Nair CR, Gupta PH, Ghauhan DP, Mehta SK (1983) Effect of vitamin A deficiency on intestinal reduced glutathione levels in rats. IRSC Medical Science 11:320–321

    Google Scholar 

  • Nebert DW, Gelboin HV (1968) Substrate-inducible microsomal aryl hydroxylase in mammalian cell culture. J Biol Chem 243:6242–6249

    Google Scholar 

  • Olson JA (1979) A simple dual assay for vitamin A and carotenoids in human liver. Nutr Rep Int 19:807–813

    Google Scholar 

  • Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239:2370–2378

    Google Scholar 

  • Ortega P, Hayes WJJ, Durham WF, Mattson A (1956) DDT in the diet of the rat. Its effect on DDT storage, liver function and cell morphology. U.S. Government Printing Office (Public Health Monograph no 43, PHS Publication no 484), Washington, DC, p 27

    Google Scholar 

  • Phillips WEJ. (1963) DDT and the metabolism of vitamin A and-carotene in the rat. Can J Physiol Pharmacol 41:1793–1802

    Google Scholar 

  • Pinkus LM, Ketley JN, Jakoby WB (1977) The glutathione S-transferases as a possible detoxification system of rat intestinal epithelium. Biochem Pharmacol 26:2359–2363

    Google Scholar 

  • Siddik ZH, Drew R, Litterst CL, Mimnaugh EG, Sikic BI, Gram TE (1980) Hepatic cytochrome P-450-dependent metabolism and enzymatic conjugation of foreign compounds in vitamin A-deficient rats. Pharmacology 21:383–390

    Google Scholar 

  • Sieber SM (1976) The lymphatic absorption ofp,p′-DDT and some structurally related compounds in the rat. Pharmacology 14:443–454

    Google Scholar 

  • Thunberg T, Ahlborg UG, Wahlstrom B (1984) Comparison between the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and six other compounds on the vitamin A storage, the UDP-glucuronosyltransferase and the aryl hydrocarbon hydroxylase activity in rat liver. Arch Toxicol 55:16–19

    Google Scholar 

  • Tredger JM, Chhabra RS, Fouts JR (1976) Postnatal development of mixed function oxidation as measured in microsomes from the small intestine and liver of rabbit. Drug Metab Dispos 4:17–23

    Google Scholar 

  • Vainio HV, Hietanen E (1980) in Concepts in Drug metabolism. part A. Jenner P and Testa B (eds) Marcel Dekker, New York, pp 33

    Google Scholar 

  • Varma RN, Beaton GH (1972) Quantitative aspects of the urinary and fecal excretion of radioactive metabolites of vitamin A in the rat. Can J Physiol Pharmacol 50:1026–1037

    Google Scholar 

  • Wolf G (1984) Multiple functions of vitamin A. Phys Rev 64:873–937

    Google Scholar 

  • Zampaglione NG, Mannering GJ (1973) Properties of benzpyrene hydroxylase in the liver, intestinal mucosa and adrenal of untreated and 3-methylcholanthrene treated rats. J Pharmacol Exp Ther 185:676–685

    Google Scholar 

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de Waziers, I., Azaïs, V. Drug-metabolizing enzyme activities in the liver and intestine of rats exposed to DDT: effects of vitamin A status. Arch. Environ. Contam. Toxicol. 16, 343–348 (1987). https://doi.org/10.1007/BF01054952

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  • DOI: https://doi.org/10.1007/BF01054952

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