Urea cycle enzyme activities are normal and inducible by a high-protein diet in CCl4 cirrhosis of rats
✍ Scribed by Philip J. Snodgrass
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 754 KB
- Volume
- 9
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
We produced moderately severe, inactive micronodular cirrhosis in rats using CCl., and measured the urea cycle enzyme activities in liver after feeding a 159" casein diet for 1 week and again after a 60% casein diet for 1 week. There was no deficiency of any of the five urea cycle enzymes in cirrhotic livers of rats pair-fed the 15% casein diet. Argininosuccinate synthetase and carbamyl phosphate synthetase activities were lower than in non-pair-fed controls by some baselines. ~1 1 five enzymes in cirrhotic livers were induced 1.5-to 3-fold by the high-protein diet expressed as units per 100 gm of rat. The level of carbamyl phosphate synthetase activity was lower in the livers of rats pair-fed the 60% casein diet than in control livers based on wet weight, collagen-free protein and DNA, but the activities were equal expressed as units per 100 gm of rat. This example of CC1,-induced cirrhosis in the rat does not serve as a good model for human cirrhosis, in which the urea cycle enzymes are reported to be decreased in activity.
cycle enzyme activities compared to control rat livers?
(;;j no cirrhotic rat livers respond to a high-protein diet by induction of all five urea cycle enzymes? The ~~~, -~~d ~~~d cirrhosis of rats is the most fiequently used animal model of this disease. We considered it important to know whether this form of cirrhosis is or is not like that in man as far as urea cycle activities are concerned. If not, this model should not be used to study waste nitrogen disposal in cirrhosis.
MATERIALS AND METHODS
Animals Diets and Production of Cirrhosis. Male
Wistar rats (Harlan Industries, Indianapolis, IN) weighing approximately 150 gm were placed on a 23% protein pelleted diet (Rodent Lab Chow 5001, Ralston Purina Co., St. Louis, MO) and given drinking wat.er containing 35 mg per dl phenoharhit,al. After 1 week, when the rats weighed about 200 gm, the first dose of CCl., was administered intragastrically (0.04 ml). Weekly thereafter, the dose was increased according to the weights recorded On bhe third and seventh day after each preceding CCI, dose, according to t,he protocol of Proctor and Chatamra (7). After 14 to 16 weeks. we stopped the CCI., and phenobarbita] and placed the rats on a diet (ICN Nutritional Biochemicals, Cleveland, OH) containing 15% casein, sucrose, optimal amounts of vitamins and minerals and cottonseed oil ( 8 ) . After 2 weeks of feeding this diet, a wedge liver biopsy was obtained under ether anesthesia to assess the severity of the cirrhosis histologically and the presence of ascites.
six cirrhotic rats (Group A) were paired with normal rats of