Influence of (+)-propoxyphene on the hexachlorobenzene-induced porphyria of rats.
The increased urinary porphyrin excretion after hexachlorobenzene (HCB) could be reduced by simultaneous application of (+)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol propionate ((+)-propoxyphene) to female Wistar rats over a period of 60 days. Total porphyrin excretion and predominantly the higher carboxylated porphyrins, such as uroporphyrin were reduced under the influence of (+)-propoxyphene. (+)-Propoxyphene led to an increase of hepatic cytochrome P-450 content and the cytochrome P-450 dependent enzymes arylhydrocarbon-hydroxylase- and aminopyrine-N-demethylase activities, whereas the 7-ethoxycoumarine-deethylase activity was not changed. The simultaneous treatment of rats with HCB and (+)-propoxyphene decreased the HCB induced cytochrome P-450 content and the aminopyrine-N-demethylase activity. The arylhydrocarbon-hydroxylase activity, however, was increased, whereas no influence on the 7-ethoxycoumarine-deethylase activity could be demonstrated by (+)-propoxyphene treatment of HCB exposed rats. It is under discussion that a reduction of aminopyrine-N-demethylase activity by the drug in the liver alters the HCB metabolism resulting in a reduced production of a probable ultimative porphyrogenic agent.
D015660:7-Alkoxycoumarin O-Dealkylase; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002722:Chlorobenzenes; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D011431:Dextropropoxyphene / Q000494:pharmacology*; D005260:Female; D006581:Hexachlorobenzene; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D011164:Porphyrias / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002722:Chlorobenzenes; D006581:Hexachlorobenzene; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; D000633:Aminopyrine N-Demethylase; D011431:Dextropropoxyphene