Hoensch H, Hartmann F, Schomerus H, Bieck P, Dölle W
Gut. 1979 Aug;20(8):666-72. doi: 10.1136/gut.20.8.666.
Monooxygenase enzymes are involved in the biotransformation of drugs and of environmental carcinogens. The activity of 7-ethoxycoumarin 0-deethylase and associated NADPH-cytochrome c reductase was determined in 9000 g supernatant from bioptically obtained liver specimens from patients with various liver diseases in order to study in vitro drug metabolising capacity. Monooxygenase and reductase activity was significantly higher in the livers of 21 patients with alcoholic liver disease (fatty liver, alcoholic hepatitis, cirrhosis of the liver) than in 22 normal controls or in six patients with chronic active hepatitis. The raised activity of drug-metabolising enzymes obtained from alcoholics with liver damage differs from normal values found in five alcoholics without liver disease. Both groups were comparable in respect to the amount of alcohol consumed and duration of abuse. A strikingly low monooxygenase activity was observed in eight patients with cirrhosis of the liver and ascites, with, however, no apparent effect on reductase activity. The results show that alcoholic liver disease is associated with enhanced monooxygenase and reductase activity, but alcoholism, per se, is not. This rise of drug-metabolising enzyme activity could lead to selectively increased rates of biotransformation in patients with alcoholic liver damage.
单加氧酶参与药物和环境致癌物的生物转化。为了研究体外药物代谢能力,测定了来自各种肝病患者活检获得的肝脏标本9000g上清液中7-乙氧基香豆素O-脱乙基酶及相关的NADPH-细胞色素c还原酶的活性。21例酒精性肝病(脂肪肝、酒精性肝炎、肝硬化)患者肝脏中的单加氧酶和还原酶活性显著高于22例正常对照者或6例慢性活动性肝炎患者。有肝损伤的酗酒者体内药物代谢酶活性升高,这与5例无肝病的酗酒者的正常数值不同。两组在饮酒量和滥用持续时间方面具有可比性。在8例肝硬化伴腹水患者中观察到单加氧酶活性显著降低,但对还原酶活性无明显影响。结果表明,酒精性肝病与单加氧酶和还原酶活性增强有关,但酗酒本身并非如此。药物代谢酶活性的这种升高可能导致酒精性肝损伤患者生物转化速率选择性增加。