Influence of (+)-propoxyphene on the hexachlorobenzene-induced porphyria of rats

Abstract

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.