Relationship between N-acetyltransferase (NAT) activity and liver protoporphyrin level in experimental porphyria

The results of our previous studies demonstrated that isonicotinic acid hydrazide (INH) can aggravate griseofulvin (GF)-induced protoporphyria in mice. To elucidate this phenomenon, we studied the relationship between liver protoporphyrin (PP) levels and N-acetyltransferase (NAT) activity, which is known to be a major catabolic enzyme of INH metabolism in the liver. The results revealed a significant correlation between liver PP levels and NAT activity in the mice fed 0.1% GF and 0.05% INH. In this group, mice with high NAT activity developed severe protoporphyria. There was no correlation, however, between liver PP levels and NAT activity in the mice fed GF alone or INH alone. The result suggested that INH metabolites formed by NAT enhance the hepatotoxicity of GF in mice.