Effect of isoniazid on folic acid status in Swiss mice and rats

Area of Science:

• Biochemistry
• Toxicology
• Pharmacology

Background:

• Isoniazid (INH) is a primary drug for tuberculosis treatment.
• INH and its metabolites can exhibit varying toxicity profiles.
• Understanding folate metabolism is crucial for drug safety and efficacy.

Purpose of the Study:

• To investigate the impact of isoniazid (INH) and its metabolites, monoacetylhydrazine (MAH) and diacetylhydrazine (DAH), on folate levels.
• To compare these effects in mice, susceptible to INH tumorigenicity, and rats, resistant to INH carcinogenicity.

Main Methods:

• Mice and rats were administered INH, MAH, diacetylhydrazine (DAH), or hydrazine sulfate (HS) via intraperitoneal injection or long-term feeding.
• Circulating and tissue folate levels were measured in treated animals.
• Species-specific responses to INH and its metabolites were analyzed.

Main Results:

• Intraperitoneal injection of INH, MAH, and HS decreased blood folates in mice.
• In rats, HS and MAH reduced blood folates, while DAH had no effect on either species.
• Long-term feeding of MAH and HS to mice led to decreased blood folates at 17 and 22 months, respectively.

Conclusions:

• Isoniazid and its metabolites, particularly MAH and HS, can deplete folate levels in rodents.
• The effect on folate levels varies between species and administration routes.
• These findings highlight potential interactions between INH therapy and folate metabolism, warranting further investigation.