Regenerative capacities of normal and cirrhotic livers following 70% hepatectomy in rats and the effect of alpha-tocopherol on cirrhotic regeneration

Abstract

Background: The regeneration of normal and cirrhotic liver has been very well demonstrated after partial hepatectomy; although the tissue regenerated by cirrhotic liver is also cirrhotic. The structural differences of the regenerated tissues between normal and cirrhotic livers may also indicate different regeneration capacities. The objective of this study was to compare the regeneration capacities of normal and cirrhotic livers by bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) labeling indices in replicating nuclei and mitotic figures in cells in partially hepatectomized normal and cirrhotic rats and to study the effect of alpha-tocopherol on cirrhotic liver regeneration.

Methods: Five groups of adult Wistar rats comprised normal livers, cirrhotic livers, regenerated normal livers, regenerated cirrhotic livers, and alpha-tocopherol-treated regenerated cirrhotic livers. Cirrhosis was induced by intragastric administration of carbon tetrachloride and phenobarbital in the drinking water of the rats. Liver regeneration capacities in normal and cirrhotic rats and following partial hepatectomy in normal and cirrhotic rats and cirrhotic rats that were administered alpha-tocopherol were evaluated through BrdU incorporation, PCNA labeling, and mitotic indices.

Results: BrdU and PCNA labeling and mitotic indices were zero for normal rats and 4.3 +/- 3.5, 6.5 +/- 5, and 2.5 +/- 1.5 for cirrhotic rats, respectively. The values after partial hepatectomy in normal and cirrhotic rats were 46.2 +/- 8.7 and 27.8 +/- 7.5 for BrdU labeling, 83.7 +/- 6.5 and 51.3 +/- 6.8 for PCNA labeling, and 31.8 +/- 4.2 and 18.6 +/- 3.4 for mitotic index, respectively. For the fifth group comprising cirrhotic rats that were administered alpha-tocopherol and had undergone partial hepatectomy, BrdU incorporation, PCNA labeling, and mitotic indices were 37.5 +/- 6.3, 76.5 +/- 6.2, and 27.2 +/- 4.2, respectively. When the cirrhotic liver regeneration group was compared with the normal liver regeneration group, rates of liver regeneration in the cirrhotic group were significantly depressed (P < 0.01). Although the BrdU incorporation and PCNA labeling indices of the alpha-tocopherol-administered cirrhotic liver regeneration group indicated significantly lower rates of liver regeneration when compared with the normal liver regeneration group (P < 0.05), the liver regeneration rates of the alpha-tocopherol-administered cirrhotic group were also significantly higher than those of the cirrhotic liver regeneration group that was not administered alpha-tocopherol (P < 0.01).

Conclusions: Cirrhotic livers revealed a significantly depressed capacity for regeneration following partial hepatectomy. alpha-Tocopherol administration seemed to improve the rates of regeneration in cirrhotic rats with respect to the BrdU incorporation, PCNA labeling, and mitotic indices.