Effect of Isoniazid on Vitamin B6 Metabolism; Its Possible Significance in Producing Isoniazid Neuritis.

Abstract

89cells shrink considerably. Erythrocytes show a similar but smaller shift both of electrolytes and water.Indoleacetic acid also causes shrinkage of the tumor cells, and loss of potassium chloride. With erythrocytes the effect was quite small, although definite shrinking was seen (3). In correspondence the indoleacetate ion showed a smaller effect than pyridoxal in the present experiments ( Fig. 1 ) .Evidence obtained with tumor cells from pyridoxine-deficient mice implicates pyridoxal in the normal process of amino acid accumulation by these cells (3,4). A close relationship to the transfer of potassium into cells is also indicated (3). Summary. Pretreatment of erythrocyteswith 10 m M pyridoxal makes the cells subsequently more-resistant to lysis by hypotonic solutions. Indoleacetic acid shows the same behavior to a smaller degree. These effects are attributed to a net loss of cell solutes in the form of potassium and chloride which the agents produce.

Quantitative Studies on Human Urinary Metabolites of Tryptophan as Affected by Isoniazid and Deoxypyridoxine1

“…Thus it may be possible that patients ingesting isoniazid convert more than the normal quantity of tryptophan to kynurenine. However, since there is so much evidence to indicate that isoniazid has an antagonistic effect on pyridoxine in man (3,5) and the metabolites found in large quantities in the urine in the present studies were identical with those detected in the urine of pyridoxinedeficient rats (12), it appears reasonable to explain the present findings in terms of incomplete metabolism of the kynurenine produced. Dalgliesh and Tabechian (30) have recently discussed the metabolic fate of tryptophan and have suggested that considerable tryptophan may normally enter this pathway and may be converted to 3-hydroxyanthranilic acid and then to non-aromatic products.…”

“…gelatin capsules (Figures 1 and 2) or as four 0.5-Gm. tablets 3 (Figures 3 through 5). The deoxypyridoxine4 was given in gelatin capsules and the isoniazid and vitamins were standard pharmaceutical preparations.…”

“…Rosen (11) reported no increase in xanthurenic acid excretion when isoniazid was administered to pyridoxine-deficient rats, even though the rats showed other signs of pyridoxine deficiency. In the studies of Biehl and Vilter (3) the administration of large doses of isoniazid resulted in a considerable increase in urinary excretion of vitamin B8, about a 40 per cent incidence of clinical evidence for pyridoxine de- it appeared that the clinical evidence for pyridoxine deficiency in rats or humans given isoniazid was more striking than the xanthurenic acid excretion studies would suggest (3,11).…”

Combined Drug Treatment of Tuberculosis. Ii. Studies of Antimicrobially-Active Isoniazid and Streptomycin Serum Levels in Adult Tuberculous Patients

“…daily without pyridoxine has led to a prohibitive increase in isoniazid neuropathy (24). The simultaneous administration of pyridoxine with isoniazid has reduced but not completely prevented toxicity due to isoniazid (24,26). Some few subjects inactivate isoniazid so rapidly that dosages of 16 to 20 mg. per Kg.…”

Kinetic Studies on Growth of Excised Root Tips of Lycopersicum esculentum

“…It was therefore reasonable to suspect that the inhibitory effect of INH is mainly concerned with the amino acid and protein nmetabolism of the plant, rather than with auxin pro- 1 Received Dec. 2, 1961. This work was carried out at the Botanical Laboratories of the University of Pennsylvania, aided by a grant from the National Science Foundation (G-6329) duction, as (17).…”