Alcoholic liver disease in rats fed ethanol as part of oral or intragastric low-carbohydrate liquid diets.
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.
Ronis
Martin J J
MJ
Department of Pharmacology and Toxicology, UAMS, Arkansas Children's Nutrition Center, Little Rock Arkansas, 72205, USA. RonisMartinJ@uams.edu
Hakkak
Reza
R
Korourian
Sohelia
S
Albano
Emanuele
E
Yoon
Seokjoo
S
Ingelman-Sundberg
Magnus
M
Lindros
Kai O
KO
Badger
Thomas M
TM
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001835:Body Weight; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004040:Dietary Carbohydrates / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D016207:Cytokines; D004040:Dietary Carbohydrates; D005609:Free Radicals; D000431:Ethanol; D008315:Malondialdehyde; D019392:Cytochrome P-450 CYP2E1