6-azauridine triacetate induced hyper beta-alaninemia and its decrease by administration of pyridoxine

• Published in: Journal of Nutritional Science and Vitaminology 1983, Vol.29(5), pp.631-635
• Main Authors: Slavik, M, Blanc, O, Smith, K.J, Slavik, J
• Format: Article
• Language: English
• Subjects: 6-azauridine triacetate; Alanine - blood; Animals; antineoplastic agents; Azauridine - analogs & derivatives; Azauridine - pharmacology; beta-Alanine - blood; Drug Interactions; Female; Male; pyridoxal phosphate; pyridoxine; Pyridoxine - pharmacology; Rabbits; β-alanine
• ISSN: 0301-4800; 1881-7742
• DOI: 10.3177/jnsv.29.631

The effect of pyridoxine on 6-azauridine triacetate (6-AzUrd-TA) induced hyper β-alaninemia was studied in New Zealand albino rabbits in three experiments. In each of the three experiments the animals were administered by gavage: Group 1 (Control), drinking water; Group 2, 6-AzUrd-TA; and Group 3, 6-AzUrd-TA with pyridoxine. While no β-alanine was found in the control group or in pretreatment samples of the 6-AzUrd-TA and 6-AzUrd-TA+pyridoxine treated animals, high concentrations of this amino acid (191.0±91.6, 220.2±116.3, 103.2±64.4 nmol/ml) were found on the fourth and seventh days of 6AzUrd-TA treatment with daily doses of 1.0g/kg and 0.5g/kg B.W. respectively. The drug induced hyper β-alaninemia was significantly (p≤0.05) reduced in all three experiments by simultaneous pyridoxine administration in daily doses of 50mg/kg B.W. These results indicate, that daily repeated oral administration of 6-AzUrd-TA causes elevation of serum β-alanine, which can be partially prevented by oral administration of pyridoxine. They also indirectly support the hypothesis, that 6-AzUrdTA induced hyper β-alaninemia is at least partially caused by the inhibition of β-alanine degrading enzymes, that use pyridoxal phosphate as a coenzyme. Direct measurement of the enzyme activity is planned in our future studies.