Hepatic sinusoidal fibrosis induced by cholesterol and stilbestrol in the rabbit: 1. Morphology and inhibition of fibrogenesis by dipyridamole

Abstract

tween individual animals. It has been shown that rabbits This study documents the hepatic morphology and the that are given CHOL simultaneously with diethylstilbestrol ultrastructure of a model of hepatic fibrosis in rabbits.(DES) rapidly develop hepatic fibrosis over a period of several Rabbits were given a cholesterol-supplemented diet weeks, 6-8 but this model has not been studied in detail. The (1%), a stilbestrol diet (10 mg subcutaneously twice a present report describes the hepatic morphology, the ultraweek), or both treatments simultaneously for 7 weeks.structure, and the hepatic collagen content following this Rabbits given the combined treatment developed sinu- The treatments were given for 7 weeks, at which point the animals were killed. One D-C rabbit died before the completion of the study. Hepatic fibrosis develops in a variety of mammals that areThe liver and spleen were exposed under sodium pentobarbital anesfed a cholesterol (CHOL)-supplemented diet.1-5 However, in thesia without prior fasting, and samples were excised, diced, and most species, including the rabbit, the fibrosis is mild, re-fixed by immersion in cold 2.5% glutaraldehyde buffered with 0.1 quires many months to develop, and is highly variable be-mol/L of cacodylate at pH 7.2. This tissue was later postfixed with osmium tetroxide, embedded in Epon 812, and the sections were stained with lead citrate and uranyl acetate. The spleens were cut Abbreviations: CHOL, cholesterol; D-C, diethylstilbestrol-cholesterol; DES, diethylstilinto 5-mm slices and allowed to drain on absorbent paper before bestrol.weighing. The liver slices were fixed in buffered 4% formaldehyde,

Effects of fat accumulation in the liver on hemodynamic variables assessed by doppler ultrasonography

“…This can be explained by the reduced flow in the hepatic microcirculation, because of sinusoidal compression by enlarged, fat-laden hepatocytes, then by the proliferation of fibroblasts with the formation of collagen bundles in the perisinusoidal space. [37][38][39][40] We found a significantly greater pv congestion index in patients with severe than with mild fat accumulation. Moriyasu et al 25 reported a 2.5fold congestion index increase in patients with cirrhosis and portal hypertension compared with the control group.…”

The anti‐inflammatory effect of celecoxib does not prevent liver fibrosis in bile duct‐ligated rats

“…However, levels of COX-1 were similar between normal and cirrhotic livers. The induction of COX-2 in the liver of 7-day BDL rats might be the result of active inflammation and the mechanism of injury could involve either accumulation of bile salts or generation of cholesterol oxidation products (23,24). COX-2 inhibitor, celecoxib, significantly lowered serum ALT activities (an indicator of hepatocellular damage) and consistently caused Specific mRNA values were normalized to the expression of GAPDH, as described in 'Materials and methods'.…”

Development Of An Experimental Model Of Liver Cirrhosis In Rabbits

“…Rabbits have been used as animal models for liver cirrhosis induced by endotoxins 15 and sinusoidal fibrosis. 16,17 Carbon tetrachloride-induced liver cirrhosis in rabbits was described by Ugazio et al, who suggested that microsomal induction by phenobarbital was not possible because of the extreme sensitivity of rabbits to the initial dose (120 L) of CCl4. 18 Furthermore, the time required for the development of cirrhosis was long (6 months).…”