The metabolism of 7-ethoxycoumarin and 7-hydroxycoumarin by rat and hairless mouse skin strips

The metabolism of 7-ethoxycoumarin and 7-hydroxycoumarin was studied in rat and hairless mouse skin strips. These preparations supported de-ethylation, sulphation and glucuronidation reactions. The de-ethylation reaction was inducible in both species by pretreatment with either 5,6-benzoflavone or 3-methylcholanthrene. The hairless mouse strips exhibited a greater basal de-ethylase activity than rat strips, although the latter was the more responsive to inducers. Accompanying the increase in de-ethylation activity was a change in the pattern of metabolites, with a large increase in the percentage of the unconjugated metabolite. When 7-hydroxycoumarin was employed as the primary substrate the glucuronide was the major metabolite formed by strips from both species. The glucuronidation and sulphation activities were unchanged by 3-methylcholanthrene pretreatment.