Inhibition of hepatic drug metabolism in the rat after Corynebacterium parvum treatment.
Inhibition of hepatic drug metabolism in the rat after Corynebacterium parvum treatment.
复制标题
小棒状杆菌治疗后大鼠肝脏药物代谢的抑制。
DOI：
10.1016/0006-2952(83)90282-4
复制
发表时间：
1983
影响因子：
5.8
通讯作者：
Loo,TL
中科院分区：
文献类型：
--
作者：
Farquhar,D;Benvenuto,JA;Kuttesch,N;Loo,TL
成年雌性Sprague-Dawley大鼠单次静脉注射短小棒状杆菌（C. parvum），剂量为10 mg/m2。苯胺羟化酶（AH）活性，氨基比林脱甲基酶（APD）活性，和细胞色素P-450浓度降低20-50%，在第3-6天，此后，逐渐恢复到控制水平的第17天。仅在第10天细胞色素还原酶活性和细胞色素b5浓度显著降低（24%）。微粒体蛋白浓度无变化。parvumadedin对AH和APD活性无影响。尽管给药大鼠的肝脏仅轻微（< 20%）增大，但总体脾肿大明显，在第6天达到最大值。一个显着的负相关存在于脾脏的大小和APD活动的时间变化之间。给药后6天处死大鼠。在0.67 - 10.00 mg/m2的剂量范围内，辅助剂量与APD活性降低幅度之间存在明显的直接关系。脾肿大和APD活性之间存在类似的关系。给药大鼠肝脏切片的组织学检查显示整个实质中存在大量肉芽肿。酶抑制的程度通常与肝脏病变的严重程度相关。
Drug-metabolizing enzyme activities, cytochrome concentration, and protein content of hepatic microsomal preparations from adult, female Sprague-Dawley rats were examined at 1-, 3-, 6-, 10-, 14- and 17-day intervals after administration of a single intravenous injection ofCorynebacterium parvum(C. parvum) at a dose of 10 mg/m2. Aniline hydroxylase (AH) activity, aminopyrine demethylase (APD) activity, and cytochrome P-450 concentration were reduced 20–50% on days 3–6 and, thereafter, gradually recovered to control levels by day 17. Cytochromecreductase activity and cytochromeb5concentration were reduced significantly (24%) only on day 10. Microsomal protein concentration was unchanged.C. parvumaddedin vitrohad no effect on AH or APD activity. Although livers of treated rats were only slightly (< 20%) enlarged, gross splenomegaly was apparent, reaching a maximum on day 6. A marked inverse correlation existed between the temporal variation in the size of the spleen and APD activity. In rats killed 6 days after administration ofC. parvumat 0.67 to 10.00 mg/m2, a direct relationship was apparent between the adjuvant dose and the magnitude of reduction of APD activity. A similar relationship was apparent between splenomegaly and APD activity. Histopathologic examination of liver sections from treated rats revealed numerous granulomas throughout the parenchyma. The magnitude of enzyme inhibition generally paralleled the severity of the hepatic lesions.