Liver Responses to Repeated Doses of Carbon Tetrachloride in Mini and Wistar Rats.

Abstract

The liver responses to repeated doses of CCl4 (0.5 mg/kg b.w., twice weekly) were compared between Wistar and Mini rats, in which the expression of growth hormone (GH) gene is suppressed by the presence of an antisense gene, at 2, 4, and 6 weeks after treatment (WAT). Fibrosis started earlier and its degree was severer in Mini rats than in Wistar rats, and hepatocyte damage was also severer in Mini rats than in Wistar rats. This corresponded well with the changes in serum AST and ALP levels. Oval cell proliferation in the fibrous septa of the liver of CCl4-treated Mini rats may also have some relations to such increase in ALP activity and fibrogenesis in Mini rats. The increase in the level of TGF-β1 mRNA was more prominent in Mini rats than in Wistar rats at 4 and 6 WAT, and this corresponded to the strain difference in the degree of liver fibrosis. The present results indicate that the responsibility of the liver to repeated doses of CCl4 was different between Mini rats and Wistar rats. Mini rats seem to be useful as a new tool in the investigation of regulatory mechanisms of GH on liver injury and regeneration.