Premium
Cholesterol supplementation prevents necrosis and inflammation but enhances fibrosis in alcoholic liver disease in the rat
Author(s) -
Nanji A A,
Rahemtulla A,
Daly T,
Khwaja S,
Miao L,
Zhao S,
Tahan S R
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510260112
Subject(s) - endocrinology , medicine , fibrosis , thromboxane b2 , fish oil , alcoholic liver disease , thromboxane , proinflammatory cytokine , corn oil , eicosanoid , cholesterol , fatty liver , lipid peroxidation , steatohepatitis , kupffer cell , cyclooxygenase , chemistry , inflammation , arachidonic acid , biology , cirrhosis , oxidative stress , biochemistry , platelet , disease , fishery , fish <actinopterygii> , enzyme
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 α (TNF‐α), cyclooxygenase (Cox)‐1 and ‐2, and transforming growth factor β (TGF‐β). 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‐α and Cox‐2 mRNAs, decreased thromboxane levels, decreased lipid peroxidation, and increased TGF‐β mRNA. Cholesterol enrichment of the diet thus decreases proinflammatory components, but enhances fibrosis in ethanol‐fed rats.