Influence of chloroquine on the porphyrin metabolism.
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 delta-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 delta-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.
D015660:7-Alkoxycoumarin O-Dealkylase; D000622:Aminolevulinic Acid / Q000652:urine; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006581:Hexachlorobenzene; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010105:Oxygenases / Q000378:metabolism; D011162:Porphobilinogen / Q000652:urine; D011164:Porphyrias / Q000139:chemically induced / Q000378:metabolism*; D011166:Porphyrins / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D011166:Porphyrins; D006581:Hexachlorobenzene; D011162:Porphobilinogen; D002738:Chloroquine; D000622:Aminolevulinic Acid; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; D000633:Aminopyrine N-Demethylase