Work

Chronic Treatment with Isoniazid Causes Protoporphyrin IX Accumulation in Mouse Liver

Year: 2016

Type: article

Abstract: Isoniazid (INH) can cause hepatotoxicity. In addition, INH is contraindicated in patients suffering from porphyrias. Our metabolomic analysis revealed that chronic treatment with INH in mice causes a hepatic accumulation of protoporphyrin IX (PPIX). PPIX is an intermediate in the heme biosynthesis pathway, and it is also known as a hepatotoxin. We further found that INH induces delta-aminolevulinate synthase 1 (ALAS1), the rate-limiting enzyme in heme biosynthesis. We also found that INH downregulates ferrochelatase (FECH), the enzyme that converts PPIX to heme. In summary, this study illustrated that chronic treatment with INH causes PPIX accumulation in mouse liver in part through ALAS1 induction and FECH downregulation. This study also highlights that drugs can disrupt the metabolic pathways of endobiotics and increase the risk of liver damage.

Source: Chemical Research in Toxicology

DOI: 10.1021/acs.chemrestox.6b00121

Authors: Madhav Sachar, Feng Li, Ke Liu, Pengcheng Wang, Jie Lu, Xiaochao Ma

Institutions: University of Pittsburgh, Baylor College of Medicine

Language: English

Topic: Drug-Induced Hepatotoxicity and Protection

Subfield: Pharmacology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of Diabetes and Digestive and Kidney Diseases