Changes in the markers related to collagen synthesis in the liver of chronically alcohol treated rats

Abstract

In order to clarify the roles of Ito cells in the development of alcoholic fibrosis, markers related to collagen synthesis in the liver were analyzed in chronically alcohol treated rats. The livers were obtained from rats fed a diet containing alcohol (alcohol group) and those fed a control diet (control group) for 4 weeks. Prolyl hydroxylase (PH) activity in the whole liver tissue did not differ in the alcohol and control groups. However, the activity in the isolated Ito cells was significantly higher in the alcohol group than in the control group. Immunoreactive PH beta-subunit contents in the liver and serum were significantly higher in the alcohol group than in the control group. Hydroxyproline contents in the liver did not differ in either groups. Immunohistochemically, type IV collagen and laminin were clearly stained along with the sinusoid in the livers of the alcohol group. However, the staining reactions were very weak in the control group. Staining reactions to types I and III collagen were very weak or almost absent in the livers of both groups. Desmin-positive cells, along with the sinusoid, increased significantly in the alcohol group, especially at the centrilobular area, suggesting that the number of Ito cell increase in the centrilobular areas of the alcohol treated rats. These results suggest that type IV collagen and laminin synthesis increase in the Ito cells of chronically alcohol treated rats, although clear evidence of hepatic fibrosis was not obtained. This increase may be related to capillarization of the sinusoids and finally to the development of perisinusoidal fibrosis in alcoholics.

Changes in type IV collagen content in livers of patients with alcoholic liver disease

“…In cultured rat liver cells, IV-C was mainly produced by Ito and endothelial cells (27). In rats treated for long periods with alcohol, prolyl hydroxylase activity in It0 cells increased and IV-C was clearly stained at the sinusoidal walls, without any evidence of hepatic fibrosis seen with routine connective tissue staining (28 results indicate that IV-C synthesis in Ito cells is increased by long-term alcohol consumption and that this increase may play an important role in the development of alcoholic fibrosis.…”

Histological changes in the liver of fetuses of alcohol-treated pregnant rats

“…These findings are consistent with the results of a study in rats by Gallo and Weinberg. 21 Takase et al 22 reported that there was clear immunohistochemical staining of type IV collagen along with the sinusoids in the livers of the alcohol-exposed fetuses, but weak staining reactions were seen in the control group. Also, they reported that total collagen synthesis, especially of type IV collagen, increased in cultured Ito cells and hepatocytes isolated from chronically alcohol-treated rats.…”