Lobular Difference in Fibrotic Changes in Rat Cirrhosis Model Induced by Carbon Tetrachloride

Abstract

The rat liver cirrhosis induced by carbon tetrachloride (CCl4) animal model is widely used in efficacy studies. In the present study, we examined the difference among hepatic lobes of fibrotic lesions in CCl4-induced liver cirrhosis rat models. Male Wistar rats were given phenobarbital which was mixed into their drinking water. CCl4 was orally administered to rats weekly for 9 weeks. The total dosage of CCl4 was 1.48 ml to 1.68 ml per animal. At necropsy, the liver was divided into lobes: left lobe, median lobe, right lobe, caudate lobe, and papillary process, and the weight of each lobe was measured. Hepatic lobes were submitted to histopathological examination, morphometric analysis of fiber composition content and hydroxyproline content. The weight ratio of lobe to whole liver markedly decreased in the median lobe and right lobe, whereas the weight ratio of lobe to whole liver of the left lobe, papillary process, and caudate lobe increased. In the median and right lobes, strong fibrotic lesions and distinct micronodular formation were observed. In the other lobes, only weak fibrotic lesions were observed. Additionally, high values in fiber composition content were observed in the median and right lobes compared with the other lobes. Hydroxyproline was also markedly higher in the median lobe than in the left lobe. These findings suggest that lobular differences in fibrotic lesions are present in CCl4-induced liver cirrhosis rat models, and that severe fibrotic lesions are induced in the median and right lobes.