Accession Number:

ADA090926

Title:

The Guinea Pig as a Model for Isoniazid-Induced Reactions

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD

Report Date:

1980-02-01

Pagination or Media Count:

9.0

Abstract:

Daily injections of isoniazid were given to evaluate the guinea pig as a model in the study of such human side effects as coagulopathy syndrome, pyridoxine deficiency and hepatic lesions. Mild hepatitis was demonstrated by increases in serum glutamic oxaloacetic transaminase and sorbitol dehydrogenase levels. Hepatic lesions ranged from focal areas of inflammatory cell infiltrate to necrosis. Cutaneous testing demonstrated that the hepatitis probably was a hypersensitivity reaction to both isoniazid and isonicotinic acid. Eosinophilia and eosinophils present in hepatic lesions also suggested a hypersensitivity reaction. Increases in prothrombin time, partial thromboplastin time and fibrin split products as well as decreases in fibrinogen and thrombocytes indicated that a coagulopathy syndrome had been produced. Specifically, a disseminated intravascular coagulation-like syndrome occurred in treated animals. Isoniazid treatment also induced a pyridoxine deficiency which was demonstrated by decreases in serum pyrixodine concentrations. This deficiency was associated with demyelination of the sciatic nerve. Because the abnormalities found in these guinea pigs were similar to those reported in man, this species appears to be a good model for studying isoniazid-induced hypersensitivity hepatitis and its possible linkage to the syndrome of disseminated intravascular coagulation.

Subject Categories:

  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE