Cocoa extract protects against early alcohol-induced liver injury in the rat.
Oxidants have been shown to be involved in alcohol-induced liver injury. This study was designed to determine whether cocoa flavonoid extract, composed mostly of epicatechin and epicatechin oligomers, protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-14 g/kg per day) and cocoa extract (400 mg/kg per day) continuously for 4 weeks using an enteral feeding protocol. Mean body weight gains ( approximately 4 g/day) were not significantly different between treatment groups. Cocoa extract did not affect average daily urine ethanol concentrations ( approximately 200mg/dL). After 4 weeks, serum alanine amino transferase levels of the ethanol group were increased nearly fourfold (110+/-16 IU/L) compared to control values (35+/-3 IU/L); this effect of ethanol was blocked by cocoa extract (60+/-6 IU/L). Additionally, enteral ethanol caused severe fat accumulation, mild inflammation, and necrosis in the liver; cocoa extract significantly blunted these changes. Increases in liver TNFalpha protein levels caused by ethanol were completely blocked by cocoa extract. Further, ethanol significantly increased the accumulation of protein adducts of 4-hydroxynonenal, a product of lipid peroxidation serving as an index of oxidative stress; again this was counteracted by the addition of cocoa extract. These results indicate that dietary flavanols such as those found in cocoa can prevent early alcohol-induced liver injury.
McKim
Stephen E
SE
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Konno
Akira
A
Gäbele
Erwin
E
Uesugi
Takehiko
T
Froh
Mathias
M
Sies
Helmut
H
Thurman
Ronald G
RG
Arteel
Gavin E
GE
D000410:Alanine Transaminase / Q000097:blood; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D002099:Cacao; D002392:Catechin / Q000627:therapeutic use*; D002446:Celiac Disease / Q000473:pathology; D004195:Disease Models, Animal; D004750:Enteral Nutrition; D000431:Ethanol / Q000008:administration & dosage; D007249:Inflammation; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D009336:Necrosis; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D015430:Weight Gain / Q000187:drug effects
D000447:Aldehydes; D010936:Plant Extracts; D011506:Proteins; D000431:Ethanol; D002392:Catechin; D000410:Alanine Transaminase; C027576:4-hydroxy-2-nonenal