6-Azauridine triacetate induced hyper .BETA.-alaninemia and its decrease by administration of pyridoxine.
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概要
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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.
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著者
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SLAVIK Jana
Laboratory of Clinical Pharmacology, Cancer Research and Treatment Center, University of Kansas Medical Center
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SLAVIK Milan
Laboratory of Clinical Pharmacology, Cancer Research and Treatment Center, University of Kansas Medical Center
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BLANC Oscar
Laboratory of Clinical Pharmacology, Cancer Research and Treatment Center, University of Kansas Medical Center
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SMITH Kenneth
Departments of Medicine, University of Kansas Medical Center