6-Azauridine triacetate induced hyper .BETA.-alaninemia and its decrease by administration of pyridoxine.

Abstract

The effect of pyridoxine on 6-azauridine triacetate (6-AzUrd-TA) induced hyper beta-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 beta-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 6-AzUrd-TA treatment with daily doses of 1.0 g/kg and 0.5 g/kg B.W. respectively. The drug induced hyper beta-alaninemia was significantly (p less than or equal to 0.05) reduced in all three experiments by simultaneous pyridoxine administration in daily doses of 50 mg/kg B. W. These results indicate, that daily repeated oral administration of 6-AzUrd-TA causes elevation of serum beta-alanine, which can be partially prevented by oral administration of pyridoxine. They also indirectly support the hypothesis, that 6-AzUrd-TA induced hyper beta-alaninemia is at least partially caused by the inhibition of beta-alanine degrading enzymes, that use pyridoxal phosphate as a coenzyme. Direct measurement of the enzyme activity is planned in our future studies.