The Synergistic Effect of Isonicotinic Acid Hydrazide (INH) and Griseofulvin (GF) on Porphyrin Metabolism

Abstract

Abnormal porphyrin metabolism can be induced by several chemicals. To investigate the synergistic effect on porphyrinopathy of isonicotinic acid hydrazide (INH) with a low concentration of griseofulvin (GF), the two chemicals were given to mice simultaneously. INH was added to drinking water at a concentration of 0.05%. GF was mixed with feed at a concentration of 0.1%. The mice (dd-y strain) were divided into four groups. Those in group A were fed normally. Group B received only 0.1% GF, group C received only 0.05% INH, and group D received both 0.1% GF and 0.05% INH. The treatment was continued for 13 to 30 weeks. After treatment, the mice were anesthetized and sacrificed. The liver and whole blood were taken for analysis of porphyrins. The results revealed a slight elevation of erythrocytic porphyrins in the groups treated with 0.1% GF or 0.05% INH alone and remarkable abnormalities in the hepatic and erythrocytic porphyrin levels of the group simultaneously treated with both chemicals. These results show that INH itself may have a small potential for the induction of porphyric abnormalities, and that the administration of INH with a low concentration of GF induces marked porphyrinopathy in dd-y strain mice.

Relationship between N‐Acetyltransferase (NAT) Activity and Liver Protoporphyrin Level in Experimental Porphyria

“…Group C (treated with INH) also showed a mild elevation of PP in the liver. These results were consistent with those in our previous report (4).…”

“…Isonicotinic acid hydrazide (INH) can also bring about a synergistic effect with GF (4). Although INH itself was found to induce only a mild elevation of liver protoporphyrin (PP) level in mice, a significant elevation of liver PP was observed when it was given in combination with GF (4).…”

Chronic Treatment with Isoniazid Causes Protoporphyrin IX Accumulation in Mouse Liver

“…This discovery explains why INH potentiates drug-induced hepatic porphyria, such as rifampicin and griseofulvin. 4, 9 In addition, this study provides a mechanistic understanding of contraindication of INH in patients with porphyrias. 10 Furthermore, this project provides a novel insight into the mechanism of INH-induced liver injury.…”

“…INH has been found to potentiate griseofulvin-induced hepatic porphyria . In addition, INH is used with extreme caution in patients with porphyrias, a group of disorders in the heme biosynthesis pathway .…”

Chronic Treatment with Isoniazid Causes Protoporphyrin IX Accumulation in Mouse Liver

“…This discovery explains why INH potentiates drug-induced hepatic porphyria, such as rifampicin and griseofulvin. 4,9 In addition, this study provides a mechanistic understanding of contraindication of INH in patients with porphyrias. 10 Furthermore, this project provides a novel insight into the mechanism of INHinduced liver injury.…”