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Influence of chloroquine on the porphyrin metabolism

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Rats were treated with the well-known porphyrogen hexachlorobenzene (HCB) to induce experimental porphyria. At the same time another group of rats was treated with chloroquine in addition to HCB. The HCB-induced increase of the urinary excretion of porphyrin precursors could thereby be reduced to normal levels and the porphyrin excretion rates were decreased significantly in comparison to those of the other group. The δ-aminolevulinate synthase in the liver of the animals was slightly increased by exclusive treatment with chloroquine, which in the HCB-treated rats chloroquine led to a dramatic decrease in the key enzyme of the porphyrin (heme)-biosynthesis.

The influence of chloroquine on the HCB-induced increase of the cytochrome P-450 content and the dependent enzymatic activities were different. The 7-ethoxycumarin deethylase and the arylhydrocarbon hydroxylase activities were not influenced, whereas the increased aminopyrine-N-demethylase activity was reduced to nearly normal levels. Our findings indicate that chloroquine acts by reduction of the δ-aminolevulinate synthase activity, probably by influencing the regulation of the key enzyme of the heme biosynthesis, which is enhanced in human porphyria cutanea tarda, as well as in the HCB-induced porphyria of the rats.

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  1. 1.

    Bickers DR (1981) Treatment of the porphyrias. J Invest Dermatol 77:107–113

  2. 2.

    Kordac V, Semradova M (1974) Treatment of porphyria cutanea tarda with chloroquine. Br J Dermatol 90:95–100

  3. 3.

    Goerz G (1979) Klinik und Therapie der Porphyria cutanea tarda. Dermatologica 159:393–399

  4. 4.

    Ippen H (1960) Entstehung und Behandlung der Porphyria cutanea tarda. Klin Wschr 38:89

  5. 5.

    Kushner JP, Steinmüller DP, Lee CR (1975) The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase. J Clin Invest 56:661–667

  6. 6.

    Taljaard JJF, Shanley BC, Stewart-Wynne EG, Deppe WM, Joubert SM (1972) Studies on low dose chloroquine therapy and the action of chloroquine in symptomatic porphyria. Br J Dermatol 87:261–269

  7. 7.

    Scholnick PL, Esptein J, Marver HS (1973) The molecular basis of the action of chloroquine in porphyria cutanea tarda. J Invest Dermatol 61:226–232

  8. 8.

    Doss M (1969) Über die Porphyrin Synthese in der Keberzellkultur unter der Einwirkung von Pharmaka und Steroiden. Z Klin Chem Klin Biochem 7:133–147

  9. 9.

    Vizethum W, Bolsen K, Simon K, Weber K, Goerz G (1980) Einfluß von Chloroquin auf die Hexachlorbenzol-induzierte Porphyrie. Arch Dermatol Res 267:123–130

  10. 10.

    Kamath SA, Rubin E (1972) Interaction of calcium with microsomes: a modified method for the rapid isolation of rat liver microsomes. Biochem Biophys Res Commun 49:52–63

  11. 11.

    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

  12. 12.

    Dehnen W, Tomingas R, Roos J (1973) A modified method for the assay of benzo(a)pyrene hydroxylase. Anal Biochem 53:373–383

  13. 13.

    Schoene B, Fleischmann RA, Remmer, v. Oldershausen HF (1972) Determination of drug metabolizing enzymes in needle biopsies of human liver. Eur J Clin Pharmacol 4:65–73

  14. 14.

    Ullrich V, Weber P (1972) The O-dealkylation of 7-ethoxycoumarin by liver microsomes. Hoppe-Seyler's Z Physiol Chem 353:1171–1177

  15. 15.

    Marver HS, Tschudy DP, Perlroth MG, Collins A (1966) δ-aminolevulinic acid synthetase. J Biol Chem 241:2803–2809

  16. 16.

    Doss M (1974) Porphyrin and porphyrin precursors. In: Curtius MC, Roth M (eds) Clin biochem, principles and methods, vol 2. De Gruyter, Berlin, p 1337

  17. 17.

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

  18. 18.

    Doss M, Schmidt A (1971) Quantitative Bestimmung von δ-Aminolavulinsäure und Porphobilinogen im Urin mit Ionenaustauschchromatographie-Fertigsäulen. Z Klin Chem Klin Biochem 9:99–102

  19. 19.

    Seubert A, Seubert S (1982) High performance liquid chromatographic analysis of porphyrins and their isomers with radial compression columns. Anal Biochem 124:303–308

  20. 20.

    Stonard MD (1975) Mixed type hepatic microsomal enzyme induction by hexachlorobenzene. Biochem Pharmacol 24:1959–1963

  21. 21.

    Vizethum W, Burkhardt F, Goerz G (1980) Enzymatic electrophoretic characterization of the hexachlorobenzene-induced cytochrome P-450 in the liver of rat. Xenobiotica 10:145–150

  22. 22.

    Strik JJTWA, Debets FMH, Koss G (1980) Chemical porphyria. In: Kimbrough RD (ed) Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins and related products. Elsevier/North Holland Biomedical Press, Amsterdam, pp 191–239

  23. 23.

    Ippen H (1977) Treatment of porphyria cutanea tarda by phlebotomy. Semin Hematol 14:253–259

  24. 24.

    Malina L, Bielicky T (1968) Gegenwartige Kenntnisse über den Wirkungsmechanismus der Antimalariamittel. Hautarzt 19:385–388

  25. 25.

    Carlson PE, Flanagan CL, Ickes CE, Alving AS (1956) Enzymatic deficiency in primaquine sensitive erythrocytes. Science 124:484

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Correspondence to G. Goerz.

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Goerz, G., Bolsen, K. & Merk, H. Influence of chloroquine on the porphyrin metabolism. Arch Dermatol Res 277, 114–117 (1985). https://doi.org/10.1007/BF00414107

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Key words

  • Hepatic porphyria
  • Chloroquine
  • Hexachlorobenzene
  • δ-Aminolevulinate synthase
  • Cytochrome P-450