Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/16/2003
Publication Date: 4/1/2004
Citation: Ronis, M.J., Hakkak, R., Korourian, S., Albano, E., Yoon, S., Ingelman-Sundberg, M., Lindros, K.O., Badger, T.M. 2004. Alcoholic liver disease in rats fed ethanol as part of oral or intragastric low-carbohydrate liquid diets. Experimental Biology and Medicine. 229: 351-360.
Interpretive Summary: We are interested in the interactions of diet, nutritional status and alcohol effects during development. This is because 1 in every 29 women who know they are pregnant continues to drink alcohol during pregnancy. This amounts to more than 130,000 women each year in the United States alone. In experimental animal models, it is clear that diet composition is an important factor in tissue damage and the severity of the injury. Recently it has been shown that dietary carbohydrate content is particularly important in this process. For example, a low carbohydrate diet increased alcoholic liver damage. Since these studies can not be conducted in human, animals are used as models for human alcohol effects. In this study, we compare the effects of alcohol in 2 rat models and found that the low carbohydrate intra-gastric model is better for the study of alcoholic liver damage in the context of normal rat growth. This model is much better at control nutritional variables and will be used in our future studies.
Technical Abstract: The intragastric administration of ethanol as part of a low-carbohydrate diet results in alcohol hepatotoxicity. We aimed to investigate whether comparable liver injury can be achieved by oral diet intake. Male Sprague-Dawley rats were fed ethanol as part of low-carbohydrate diets for 36-42 days either intragastrically or orally. Liver pathology, blood ethanol concentration, serum alanine amino transferase (ALT), endotoxin level, hepatic CYP2E1 induction, and cytokine profiles were assessed. Both oral and intragastric low-carbohydrate ethanol diets resulted in marked steatosis with additional inflammation and necrosis accompanied by significantly increased serum ALT, high levels of CYP2E1 expression, and production of auto-antibodies against malondialdehyde and hydroxyethyl free radical protein adducts. However, cytokine profiles differed substantially between the groups, with significantly lower mRNA expression of the anti-inflammatory cytokine interleukin 4 observed in rats fed low-carbohydrate diets orally. Inflammation and necrosis were significantly greater in rats receiving low-carbohydrate alcohol diets intragastrically than orally. This was associated with a significant increase in liver tumor necrosis factor (alpha) and interleukin 1ß gene expression in the intragastric model. Thus, oral low-carbohydrate diets produce more ethanol-induced liver pathology than oral high-carbohydrate diets, but hepatotoxicity is more severe when a low-carbohydrate diet plus ethanol is infused intragastrically and is accompanied by significant increases in levels of proinflammatory cytokines. Key words: ethanol; hepatoxicity; low carbohydrate; rats; oral diets; total enteral nutrition