Fibrosis Accelerates the Development of Enzyme–Altered Lesions in the Rat Liver

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Abstract
Injection of pig serum into rats twice a week for 8 weeks induced stellate cell activation resulting in liver fibrosis without parenchymal cell injury. Administration of a choline deficient L–amino acid defined (CDAA) diet for 6 weeks with or without pig serum pretreatment led to the development of preneoplastic lesions that were positive for the placental form of glutathione S–transferase (GSTP). Pig serum pretreatment induced more activated stellate cells in the livers of rats subsequently fed a CDAA diet for 6 weeks compared with rats fed the CDAA diet alone. Activated stellate cells were detected as α smooth muscle actin (αSMA)–positive cells and by the expression of αSMA messenger RNA. These cells caused severe fibrosis as assessed by the hepatic hydroxyproline content. Pre–existing fibrosis induced by the activation of stellate cells with pig serum pretreatment increased hepatic malondialdehyde (MDA) level in parallel with GSTP–positive lesions. These results indicate that pre–existing fibrosis with the activated stellate cells accelerates the development of preneoplastic lesions in a CDAA diet model.

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