Abstract
A choline-deficient L-amino acid-defined (CDAA) diet led to the development of liver cirrhosis in 100% of male Wistar rats after 15 weeks and liver neoplasms in 90% of rats after one year. Concurrent administration of a prolyl 4- hydroxylase inhibitor (HOE 077) [2,4-pyridine dicarboxylic acid bis (2-methoxyethy- lamide)] at a dose of 200 ppm as an antifibrotic agent to rats fed a CDAA diet reduced the increase in liver hydroxyproline content without reduction of serum ALT. HOE 077 prevented the activation of stellate cells, as determined histologically, as well as the expression of procollagen type I mRNA, resulting in reduced hydroxyproline levels in the liver. Also, the administration of a CDAA diet for 15 weeks led to a substantial induction of GSTP-positive lesions and the production of 8-hydroxy- deoxyguanosine (8OHdG) in the liver. The concurrent administration of HOE 077 reduced the area of GSTP-positive lesions, in parallel with the reduction in hydroxyproline content. Administration of HOE 077 for 1 year reduced the development of liver neoplasms to 50% of rats fed a CDAA diet with reduced hydroxyproline and 8OHdG content. These data suggest that inhibition of fibrosis may prevent the development of neoplasms.
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© 2000 Springer Japan
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Sakaida, I., Hironaka, K., Okita, K. (2000). Prevention of Hepatocarcinogenesis by Fibrosuppression. In: Okita, K. (eds) Progress in Hepatocellular Carcinoma Treatment. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67913-4_10
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DOI: https://doi.org/10.1007/978-4-431-67913-4_10
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