Changes in the expression of genes related to apoptosis and fibrosis pathways in CCl4-treated rats.

Chronic liver diseases are accompanied by changes in the biochemical pathways related to the regulation of apoptosis and extra-cellular matrix deposition. The present study was designed to investigate, using low density arrays, changes in the hepatic gene expression together with hepatic biochemical and histological alterations in rats that had liver impairment induced by chronic exposure to CCl(4). Further, we examined the possible recovery of genetic and pathological changes following the cessation of the hepatotoxic injury. Experimental fibrosis was induced in male Wistar rats by CCl(4) administration. Animals were subdivided into two groups. One group was given CCl(4 )and animals were killed at 8 and 12 weeks of treatment. The other group was treated with CCl(4) for 6 weeks, the CCl(4 )was then stopped and, subsequently, subgroups of animals were killed after 1 and 2 weeks of recovery. CCl(4) administration over 12 weeks was associated with significant changes in B-cell leukemia/lymphoma 2, procollagen type I alpha 2, matrix metalloproteinases 3 and 8, tissue inhibitors of metalloproteinases 1, 2, and 3 and the inhibitor of apoptosis 4 gene expressions. Recovery after CCl(4) cessation was associated with changes in procollagen type I alpha 2, matrix metalloproteinase 7, tissue inhibitors of metalloproteinases 1 and 2, inhibitor of apoptosis 4, and survivin gene expressions. This study shows an association between changes in the expression of several genes regulating hepatic cell apoptosis, the fibrosis process, and the recovery of the hepatic function after removal of the toxic injury.