Mild hepatic fibrosis in cholesterol and sodium cholate diet-fed rats

To date, the majority of research on hypercholesterolemia has focused on the effects of a high cholesterol diet on atheroscle-rosis and coronary heart disease. The toxic effects of cholesterol on the liver and the relationship between the intake of a high cholesterol diet and hepatic fibrosis, however, have not been investigated cleas1y or histopethologically. Male Wistar rats were fed a dici supple-mented with 1.0% cholesterol and 0.3% sodium cholate for 12 weeks. Rats were sacnftced and analyzed via blood biochemistry, tradi-tional microscopy and immunohistochmistry. Following the feeding of this diet, the rates of asparsaze aminoiransferase. alanine aminotransfersac, Lactate dehydrogenase and total cholesterol in the rats were elevated consistently from week 3 and throughout the remainder of the experiment. From microscopic observation. hepatic necrosis. macropliage infiltration and steatosis increased markedly throughout the expenment Hepatic fibrosis and myofibmblast proliferation were detected at weeks 9 and 12. Mast cell appearance was proportional to the degree of hepatic damage. These findings suggest that hepatic fibrosis is inducible by a high cholesterol diet and is likely the result of the interaction between several different cell types (i.e., macrophages, myofibroblasts. and mast cells) in an inflame-matcay milieu. Hypercholesterolemia should be considered as a risk factor for hepatic fibrosis as well as atherosclerosis and coronary artery disease.