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

Background. The regeneration of normal and cirrhotic liver has been very we ll demonstrated after partial hepatectomy; although the tissue regenerated by cirrhotic liver is also cirrhotic. The structural differences of the reg enerated tissues between normal and cirrhotic livers may also indicate diff erent regeneration capacities. The objective of this study was to compare t he regeneration capacities of normal and cirrhotic livers by bromodeoxyurid ine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) labe ling indices in replicating nuclei and mitotic figures in cells in partiall y hepatectomized normal and cirrhotic rats and to study the effect of alpha -tocopherol on cirrhotic liver regeneration. Methods. Five groups of adult Wister rats comprised normal livers, cirrhoti c livers, regenerated normal livers, regenerated cirrhotic livers, and alph a-tocopherol-treated regenerated cirrhotic livers. Cirrhosis was induced by intragastric administration of carbon tetrachloride and phenobarbital in t he drinking water of the rats. Liver regeneration capacities in normal and cirrhotic rats and following partial hepatectomy in normal and cirrhotic ra ts and cirrhotic rats that were administered alpha-tocopherol were evaluate d through BrdU incorporation, PCNA labeling, and mitotic indices. Results. BrdU and PCNA labeling and mitotic indices were zero for normal ra ts and 4.3 +/- 3.5, 6.5 +/- 5, and 2.5 +/- 1.5 for cirrhotic rats, respecti vely. The values after partial hepatectomy in normal and cirrhotic rats wer e 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 inde x, respectively. For the fifth group comprising cirrhotic rats that were ad ministered alpha-tocopherol and had undergone partial hepatectomy, BrdU inc orporation, 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-t ocopherol-administered cirrhotic liver regeneration group indicated signifi cantly lower rates of liver regeneration when compared with the normal live r 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 f or regeneration following partial hepatectomy, alpha-Tocopherol administrat ion seemed to improve the rates of regeneration in cirrhotic rats with resp ect to the BrdU incorporation, PCNA labeling, and mitotic indices. (C) 2000 Academic Press.