Cholesterol supplementation prevents necrosis and inflammation but enhances fibrosis in alcoholic liver disease in the rat.
Based on studies that show a role for the low-density lipoprotein (LDL)-receptor in arachidonic acid delivery and eicosanoid synthesis in macrophages, the present study investigated the effect of cholesterol supplementation on pathological changes and thromboxane (TX) synthesis in alcoholic liver injury. Male Wistar rats were intragastrically fed ethanol with either corn oil or fish oil for 1 month. Control rats received isocaloric amounts of dextrose instead of ethanol. An additional group of rats fed either ethanol or dextrose with fish oil or corn oil were supplemented with 1% cholesterol. At the time of killing, all rats had the following evaluated: liver histopathology, lipid peroxidation, liver and plasma thromboxane levels, plasma endotoxin and messenger RNA (mRNA) levels of LDL-receptor, tumor necrosis factor alpha (TNF-alpha), cyclooxygenase (Cox)-1 and -2, and transforming growth factor beta (TGF-beta). Rats fed ethanol with either fish oil or corn oil developed fatty liver, necrosis, inflammation, and central vein collagen deposition. Cholesterol supplementation enhanced the degree of fibrosis but prevented necrosis and inflammation. These alterations in pathological changes by cholesterol were accompanied by absent TNF-alpha and Cox-2 mRNAs, decreased thromboxane levels, decreased lipid peroxidation, and increased TGF-beta mRNA. Cholesterol enrichment of the diet thus decreases proinflammatory components, but enhances fibrosis in ethanol-fed rats.
Nanji
A A
AA
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Rahemtulla
A
A
Daly
T
T
Khwaja
S
S
Miao
L
L
Zhao
S
S
Tahan
S R
SR
D000818:Animals; D002784:Cholesterol / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000517:prevention & control; D008108:Liver Diseases, Alcoholic / Q000473:pathology*; D008297:Male; D009336:Necrosis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D008055:Lipids; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013929:Thromboxane B2; D002784:Cholesterol