Skip to main content
Bulletin of the World Health Organization logoLink to Bulletin of the World Health Organization
. 1967;36(5):853–870.

Effect of pyridoxine on vitamin B6 concentrations and glutamic-oxaloacetic transaminase activity in whole blood of tuberculous patients receiving high-dosage isoniazid, *,

D V Krishnamurthy, J B Selkon, K Ramachandran, S Devadatta, D A Mitchison, S Radhakrishna, H Stott
PMCID: PMC2476320  PMID: 4866185

Abstract

An earlier report from the Tuberculosis Chemotherapy Centre, Madras, showed that, in tuberculous patients receiving high-dosage isoniazid (12.5-15.6 mg/kg body-weight), the concomitant administration of 6 mg of pyridoxine prevented peripheral neuropathy. In that study, biochemical determinations of B6 concentrations and GOT activity in whole blood had been routinely undertaken on all patients on admission to treatment, and at 6, 12, 24 and 52 weeks thereafter; in addition, extra determinations were undertaken for patients who developed peripheral neuropathy. The present paper reports the findings of these investigations, which are: (a) peripheral neuropathy developed predominantly among slow inactivators of isoniazid, and was associated with a substantial reduction in GOT activity but no apparent change in B6 concentration; (b) the reduction in GOT activity appeared to be due to deficiency of both the coenzyme (pyridoxal phosphate) and the apoenzyme; (c) the concomitant administration of pyridoxine (6 mg or 48 mg) with high-dosage isoniazid to 3 patients with peripheral neuropathy, 1 of whom had convulsions also, resulted in increased B6 concentrations and GOT activity, and no further convulsions; and (d) the concomitant administration of pyridoxine 6 mg daily, as a prophylactic, resulted in a significant increase in B6 concentrations and GOT activity and prevention of the neuropathy.

These findings establish the existence of a definite association between the occurrence of isoniazid-induced toxicity and diminished pyridoxine function.

Full text

PDF
853

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ADAMSON C., IKARD S., TCHERTKOFF I., YILMAZ R. Large dose isoniazid regimen for pulmonary tuberculosis; effect of glutamic acid; management of drug toxicity with pyridoxine. Sea View Hosp Bull. 1956 Jul;16(2):62–79. [PubMed] [Google Scholar]
  2. BERGERET B., CHATAGNER F., FROMAGEOT C. Quelques relations entre le phosphate de pyridoxal et la décarboxylation de l'acide cystéinesulfinique par divers organes du rat normal ou du rat carencé en vitamine B6. Biochim Biophys Acta. 1955 May;17(1):128–135. doi: 10.1016/0006-3002(55)90327-9. [DOI] [PubMed] [Google Scholar]
  3. BIEHL J. P., VILTER R. W. Effect of isoniazid on vitamin B6 metabolism; its possible significance in producing isoniazid neuritis. Proc Soc Exp Biol Med. 1954 Mar;85(3):389–392. doi: 10.3181/00379727-85-20891. [DOI] [PubMed] [Google Scholar]
  4. BOXER G. E., PRUSS M. P., GOODHART R. S. Pyridoxal-5-phosphoric acid in whole blood and isolated leukocytes of man and animals. J Nutr. 1957 Dec 10;63(4):623–636. doi: 10.1093/jn/63.4.623. [DOI] [PubMed] [Google Scholar]
  5. BRAUNSTEIN A. E. Les voices principales de l'assimilation et dissimilation de l'azote chez les animaux. Adv Enzymol Relat Subj Biochem. 1957;19:335–389. [PubMed] [Google Scholar]
  6. DAVIDSON A. N. The mechanism of the inhibition of decarboxylase by isonicotinyl hydrazide. Biochim Biophys Acta. 1956 Jan;19(1):131–140. doi: 10.1016/0006-3002(56)90394-8. [DOI] [PubMed] [Google Scholar]
  7. DEVADATTA S., GANGADHARAM P. R., ANDREWS R. H., FOX W., RAMAKRISHNAN C. V., SELKON J. B., VELU S. Peripheral neuritis due to isoniazid. Bull World Health Organ. 1960;23:587–598. [PMC free article] [PubMed] [Google Scholar]
  8. GANGADHARAM P. R., BHATIA A. L., RADHAKRISHNA S., SELKON J. B. Rate of inactivation of isoniazid in South Indian patients with pulmonary tuberculosis. Bull World Health Organ. 1961;25:765–777. [PMC free article] [PubMed] [Google Scholar]
  9. GANGADHARAM P. R., MITCHISON D. A., SUBBAIAH T. V., SHORT E. I. [The detection of isoniazid in urine]. Tubercle. 1958 Aug;39(4):191–200. doi: 10.1016/s0041-3879(58)80067-7. [DOI] [PubMed] [Google Scholar]
  10. HOPE D. B. Pyridoxal phosphate as the coenzyme of the mammalian decarboxylase for L-cysteine sulphinic and L-cysteic acids. Biochem J. 1955 Mar;59(3):497–500. doi: 10.1042/bj0590497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. JENKINS W. T., ORLOWSKI S., SIZER I. W. Glutamic aspartic transaminase. III. Inhibition by isoniazid. J Biol Chem. 1959 Oct;234:2657–2660. [PubMed] [Google Scholar]
  12. KILLAM K. F. Possible role of gammaaminobutyric acid as an inhibitory transmitter. Fed Proc. 1958 Dec;17(4):1018–1024. [PubMed] [Google Scholar]
  13. MARSH M. E., GREENBERG L. D., RINEHART J. F. The relationship between pyridoxine ingestion and transaminase activity. I. Blood hemolysates. J Nutr. 1955 May 10;56(1):115–127. doi: 10.1093/jn/56.1.115. [DOI] [PubMed] [Google Scholar]
  14. McCormick D. B., Snell E. E. PYRIDOXAL KINASE OF HUMAN BRAIN AND ITS INHIBITION BY HYDRAZINE DERIVATIVES. Proc Natl Acad Sci U S A. 1959 Sep;45(9):1371–1379. doi: 10.1073/pnas.45.9.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. NAKADA H. I. GLUTAMIC-GLYCINE TRANSAMINASE FROM RAT LIVER. J Biol Chem. 1964 Feb;239:468–471. [PubMed] [Google Scholar]
  16. OESTREICHER R., DRESSLER S. H., MIDDLEBROOK G. Peripheral neuritis in tuberculous patients treated with isoniazid. Am Rev Tuberc. 1954 Sep;70(3):504–508. doi: 10.1164/art.1954.70.3.504. [DOI] [PubMed] [Google Scholar]
  17. RAMAKRISHNAN C. V., RAJENDRAN K., JACOB P. G., FOX W., RADHAKRISHNA S. The role of diet in the treatment of pulmonary tuberculosis. An evaluation in a controlled chemotherapy study in home and sanatorium patients in South India. Bull World Health Organ. 1961;25:339–359. [PMC free article] [PubMed] [Google Scholar]
  18. Ramakrishnan C. V., Rajendran K., Mohan K., Fox W., Radhakrishna S. The diet, physical activity and accommodation of patients with quiescent pulmonary tuberculosis in a poor South Indian community. A four-year follow-up study. Bull World Health Organ. 1966;34(4):553–571. [PMC free article] [PubMed] [Google Scholar]
  19. SASS M., MURPHY G. T. The effect of isonicotinic acid hydrazide and vitamin B6 on glutamic-oxalacetic transaminase levels in whole blood. Am J Clin Nutr. 1958 Jul-Aug;6(4):424–429. doi: 10.1093/ajcn/6.4.424. [DOI] [PubMed] [Google Scholar]
  20. SHORT E. I. Studies on the inactivation of isonicotinyl acid hydrazide in normal subjects and tuberculous patients. Tubercle. 1962 Mar;43:33–42. doi: 10.1016/s0041-3879(62)80046-4. [DOI] [PubMed] [Google Scholar]
  21. TONHAZY N. E., WHITE N. G., UMBREIT W. W. A rapid method for the estimation of the glutamic-aspartic transaminase in tissues and its application to radiation sickness. Arch Biochem. 1950 Aug;28(1):36–42. [PubMed] [Google Scholar]
  22. TOWER D. B. Neurochemical aspects of pyridoxine metabolism and function. Am J Clin Nutr. 1956 Jul-Aug;4(4):329–345. doi: 10.1093/ajcn/4.4.329. [DOI] [PubMed] [Google Scholar]
  23. WACHSTEIN M., MOORE C. Pyridoxal phosphate (B6-al-PO4) levels in organs, leukocytes and blood of rats with developing vit. B6 deficiency. Proc Soc Exp Biol Med. 1958 Apr;97(4):905–909. doi: 10.3181/00379727-97-23918. [DOI] [PubMed] [Google Scholar]
  24. WADA H., MORISUE T., SAKAMOTO Y., ICHIHARA K. Quantitative determination of pyridoxal-phosphate by apotryptophanase of Escherichia coli. J Vitaminol (Kyoto) 1957 Sep 10;3(3):183–188. doi: 10.5925/jnsv1954.3.183. [DOI] [PubMed] [Google Scholar]
  25. WISSLER H. [Staphylococcal pneumonia in children]. Schweiz Med Wochenschr. 1961 Apr 8;91:134–148. [PubMed] [Google Scholar]
  26. YATZIDIS H. Measurement of transaminases in serum. Nature. 1960 Apr 2;186:79–80. doi: 10.1038/186079a0. [DOI] [PubMed] [Google Scholar]
  27. YONEDA M., ASANO N. Competitive action of isonicotinic acid hydrazide and pyridoxal in the amino acid decarboxylation of Escherichia coli. Science. 1953 Mar 13;117(3037):277–279. doi: 10.1126/science.117.3037.277. [DOI] [PubMed] [Google Scholar]
  28. YONEDA M., KATO N., OKAJIMA M. Competitive action of isonicotinic acid hydrazide and vitamin B6 in the formation of indole by E. coli. Nature. 1952 Nov 8;170(4332):803–803. doi: 10.1038/170803a0. [DOI] [PubMed] [Google Scholar]

Articles from Bulletin of the World Health Organization are provided here courtesy of World Health Organization

RESOURCES