De la Iglesia F A, McGuire E J, Feuer G
Toxicology. 1975 Jul;4(3):305-14. doi: 10.1016/0300-483x(75)90053-0.
Coumarin and 4-methylcoumarin constitue chemicals widely available in foodstuffs and coumarin-induced hepatotoxicity has been characterized in laboratory animals. The present studies were undertaken to analyze the effects of these compounds on the structure of endoplasmic reticulum membranes. The liver of rats treated for seven days with 1 mmole/kg of either coumarin or 4-methylcoumarin were subjected to quantitative sterologic analysis and various morphometric parameters were determined. Coumarin induced cytoplasmic enlargement while 4-methylcoumarin produced changes in the endoplasmic reticulum and Golgi aratus (GOL) without altering cell size. Both compounds caused a significant overall reduction of smooth-surfaced (SER) membranes. Since 4-methylcoumarin stimulates drug metabolism, this indicates that conformational changes must have taken place in the membrane arrangement. On the other hand, the reduction of membranes by coumarin is accompanied by reduced enzyme activity and phospholipid metabolism, suggesting an impairment of membrane synthesis mircosopical examinations provides a useful and sensitive tool to study the effects of foreign compounds in the liver.
香豆素和4-甲基香豆素是食品中广泛存在的化学物质，香豆素诱导的肝毒性已在实验动物中得到表征。本研究旨在分析这些化合物对内质网膜结构的影响。用1毫摩尔/千克香豆素或4-甲基香豆素处理7天的大鼠肝脏进行了定量体视学分析，并测定了各种形态计量学参数。香豆素诱导细胞质肿大，而4-甲基香豆素使内质网和高尔基体（GOL）发生变化，而不改变细胞大小。两种化合物均导致光滑表面（SER）膜显著减少。由于4-甲基香豆素刺激药物代谢，这表明膜排列中一定发生了构象变化。另一方面，香豆素导致的膜减少伴随着酶活性和磷脂代谢的降低，提示膜合成受损。微观检查为研究外来化合物对肝脏的影响提供了一种有用且敏感的工具。
