Mild Hepatic Fibrosis in Cholesterol and Sodium Cholate Diet-Fed Rats

Abstract

ABSTRACT. To date, the majority of research on hypercholesterolemia has focused on the effects of a high cholesterol diet on atherosclerosis 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 clearly or histopathologically. Male Wistar rats were fed a diet supplemented with 1.0% cholesterol and 0.3% sodium cholate for 12 weeks. Rats were sacrificed and analyzed via blood biochemistry, traditional microscopy and immunohistochemistry. Following the feeding of this diet, the rates of aspartate aminotransferase, alanine aminotransferase, 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, macrophage infiltration and steatosis increased markedly throughout the experiment. Hepatic fibrosis and myofibroblast 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 inflammatory milieu. Hypercholesterolemia should be considered as a risk factor for hepatic fibrosis as well as atherosclerosis and coronary artery disease.

Hypolipidemic effects ofSolidago chilensishydroalcoholic extract and its major isolated constituent quercetrin in cholesterol-fed rats

“…A high-cholesterol diet with cholic acid led to liver steatosis, inflammation, and fibrosis in a previous study (Jeong et al, 2005). Our results showed that despite the increased liver weight resulting from the cholesterol-enriched diet, it was unlikely to induce hepatic damage as evidenced by the lack of change in serum levels of ALT, a useful indicator of hepatic function (Kew, 2000).…”

Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet

“…The reverse transcription of 100 ng of total RNA (the same sample used for the microarray analysis) was performed with Oligo(dT) [12][13][14][15][16][17][18] primer and SuperScript III reverse transcriptase (Invitrogen, Carlsbad, CA). PCR was performed on an ABI-Prism 7900HT (Applied Biosystems).…”

“…Because the diet produces not only an Ath lipoprotein profile but also vascular fatty streak lesions, it has been widely used to study atherosclerosis in animals, including mice. 12 Although the Ath diet has recently been reported to induce liver steatosis, inflammation, and fibrosis, 13 lipid metabolism, insulin resistance, and hepatic gene expression profiles responsible for liver pathology remain to be determined in this model. To address this issue, we investigated the time course of the pathological changes and gene expression profiles of the liver in mice fed the Ath diet.…”

Persimmon (Diospyros Kaki Thunb ‘Saijo’) Peel Improved Dyslipidemia and its Related Production of Atherogenic Autoantigen Complexes in Low- Density Lipoprotein Receptor-Deficient Mice

“…This diet has been shown to induce cholesterol gallstone disease in inbred mouse strains and chronic hepatic inflammation and fibrosis in rats [44], increase production of reactive oxygen species [45], and increase platelet-leukocyte interaction [46]. It has been reported that urinary 11-dhTXB 2 significantly increased in the cirrhotic patients in comparison with the controls [47].…”