Alcoholic liver disease in rats fed ethanol as part of oral or intragastric low-carbohydrate liquid diets.

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 1beta 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.

• Authors: Martin J J Ronis, Reza Hakkak, Sohelia Korourian, Emanuele Albano, Seokjoo Yoon, Magnus Ingelman-Sundberg, Kai O Lindros, Thomas M Badger
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 229 Issue 4 Pg. 351-60 (Apr 2004) ISSN: 1535-3702 [Print] England
• PMID: 15044719 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Cytokines
• Dietary Carbohydrates
• Free Radicals
• Ethanol
• Malondialdehyde
• Cytochrome P-450 CYP2E1

Topics

• Animals
• Antibodies (metabolism)
• Body Weight
• Cytochrome P-450 CYP2E1 (metabolism)
• Cytokines (genetics, metabolism)
• Diet
• Dietary Carbohydrates (metabolism)
• Ethanol (administration & dosage, blood, toxicity)
• Free Radicals (metabolism)
• Humans
• Liver (metabolism, pathology)
• Liver Diseases, Alcoholic (metabolism, pathology)
• Male
• Malondialdehyde (metabolism)
• Rats
• Rats, Sprague-Dawley