Kündiger R, Müller R, Bien E, Skorka G
Pharmazie. 1979 Nov;34(11):736-9.
The authors investigated the effects of the administration of thioacetamide, carbon tetrachloride and aminophenazone on the excretion of ascorbic acid and hippuric acid in adult male and female Wistar rats. After a single application of thioacetamide and aminophenazone, the ascorbic acid content in the urine showed a dose-dependent increase, whereas that in the liver had decreased. This increase in the urinary ascorbic acid might be due to a release of stored ascorbic acid from the liver cells. When thioacetamide was given for a prolonged period, the ascorbic acid content in the urine increased at the beginning; later one, at the end of three weeks, it was slightly inferior to the control value. Both single and repeated applications of thioacetamide led to a decrease in the excretion of hippuric acid in the urine, which is attributed to an impairment of the mitochondrial hippuric acid synthesis. Long-term treatment with aminophenazone resulted in an increase of ascorbic acid in the urine, which is indicative of an induction effect, whereas the ascorbic acid content in the liver remained unchanged. There was no effect on the excretion of hippuric acid. In regard to their use in the toxicological evaluation of drugs, these two metabolic effects offer no decisive advantage over current liver function tests.
作者研究了硫代乙酰胺、四氯化碳和氨基苯乙酮对成年雄性和雌性Wistar大鼠抗坏血酸和马尿酸排泄的影响。单次给予硫代乙酰胺和氨基苯乙酮后，尿中抗坏血酸含量呈剂量依赖性增加，而肝脏中的抗坏血酸含量则降低。尿中抗坏血酸的这种增加可能是由于肝细胞中储存的抗坏血酸释放所致。长期给予硫代乙酰胺时，尿中抗坏血酸含量起初增加；但在三周结束时，略低于对照值。单次和重复给予硫代乙酰胺均导致尿中马尿酸排泄减少，这归因于线粒体马尿酸合成受损。长期用氨基苯乙酮治疗导致尿中抗坏血酸增加，这表明有诱导作用，而肝脏中的抗坏血酸含量保持不变。对马尿酸排泄没有影响。就它们在药物毒理学评价中的应用而言，这两种代谢效应相对于目前的肝功能测试没有决定性优势。
