EXPERIMENTAL RE-EVALUATION STUDIES ON ISONICOTINIC ACID HYDRAZIDE lN VITRO AND IN VIVO V. Influences of Glutamic Acid Against Toxicity and Therapeutic Effects of Isonicotinic Acid Hydrazide (INH) in Mice

Abstract

An account of neutralization of toxicity or administration of high doses of INH many INH derivatives and neutralizing substances against INH toxicity are still under study. Particularly, vitamin B6 is Reported. as one fo the most effective substances against chronic INH toxicity, but this vitamin neutralizes the inhibitory activity of INH to tubercle bacilli in vitro according to some investigators. Glutamic acid has been reported as a substance which antagonizes the toxic properties of INH without destroying its potency. The authors studied the influences of glutamic acid against toxicity and therapeutic effects of INH on mice and the following conclusions have been reached 1. Daily administered maximum dose of glutamic acid was more than 2,400mg. per kg in the uniform SM-strain mice. 2. 240gm per kg and 480 mg per kg of INH which were acute lethal dose were antagonized by glutamic acid pre-treatment in volume of ten-time dose of INH in mice and markedly prolonged time of death of mice. 3. When 2,400mg per kg of glutamic acid was combined in simultaneously daily administrations of 240mg per kg of INH the acute lethal dose could not kill the mice during six days. 4. Absorbtion of glutamic acid administered orally into blood stream may antagonize the lethal toxicity of INH administered subcutaneously in mice. 5. Anti-tuberculous efficacy of INH did not decrease by simultaneous administration of glutamic acid to mice. 6. In administration of high doses of INH, simultaneous administration of glutamic acid in volume of 10 time of INH dosage neutralized INH toxicity and also inhibited development of INH-resistant tubercle bacilli in mice. 7. Combined therapy of INH with glutamic acid can be recommended as one of the effective chemotherapeutic methods against tuberculosis.