Coumarin and 4-methylcoumarin induced changes in the hepatic endoplasmic reticulum studied by quantitiative sterelogy

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.