Medium-chain triglycerides inhibit free radical formation and TNF-alpha production in rats given enteral ethanol.
This study determined whether free radical formation by the liver, tumor necrosis factor (TNF)-alpha production by isolated Kupffer cells, and plasma endotoxin are affected by dietary saturated fat. Rats were fed enteral ethanol and corn oil (E-CO) or medium-chain triglycerides (E-MCT) and control rats received corn oil (C-CO) or medium-chain triglycerides (C-MCT) for 2 wk. E-CO rats developed moderate fatty infiltration and slight inflammation; however, E-MCT prevented liver injury. Serum aspartate aminotransferase levels, gut permeability, and plasma endotoxin doubled with E-CO but were blunted approximately 50% with E-MCT. In Kupffer cells from E-CO rats, intracellular calcium was elevated by lipopolysaccharide (LPS) in a dose-dependent manner. In cells from E-MCT rats, increases were blunted by approximately 40-50% at all concentrations of LPS. The LPS-induced increase in TNF-alpha production by Kupffer cells was dose dependent and was blunted by 40% by MCT. E-CO increased radical adducts and was reduced approximately 50% by MCT. MCT prevent early alcohol-induced liver injury, in part, by inhibition of free radical formation and TNF-alpha production by inhibition of endotoxin-mediated activation of Kupffer cells.
Kono
H
H
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill 27599-7365, USA.
Enomoto
N
N
Connor
H D
HD
Wheeler
M D
MD
Bradford
B U
BU
Rivera
C A
CA
Kadiiska
M B
MB
Mason
R P
RP
Thurman
R G
RG
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D003314:Corn Oil / Q000494:pharmacology; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D004731:Endotoxins / Q000097:blood; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology / Q000652:urine; D005609:Free Radicals / Q000037:antagonists & inhibitors; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000502:physiology; D007422:Intestines / Q000473:pathology; D007728:Kupffer Cells / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009994:Osmolar Concentration; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000737:chemistry* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D004042:Dietary Fats, Unsaturated; D004731:Endotoxins; D005609:Free Radicals; D018950:Lipopolysaccharide Receptors; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D003314:Corn Oil; D001219:Aspartate Aminotransferases