Inhibition of increases in ornithine decarboxylase and putrescine has no effect on rat liver regeneration.

Polyamines are considered critical for cell proliferation. During liver regeneration in the rat, ornithine decarboxylase (ODC) mRNA and enzyme activity and polyamines (primarily putrescine and spermidine) are known to increase substantially. We examined the effect of inhibition of polyamine synthesis with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of the ODC enzyme, on regenerating liver weight and total DNA, RNA, and protein, [3H]thymidine and [14C]leucine incorporation, number of mitotic figures, and putrescine, spermidine, and spermine contents.

Aging alters ornithine decarboxylase and decreases polyamines in regenerating rat liver but putrescine replacement has no effect.

Aging decreases rat liver regeneration. We (1) compared the expression of ornithine decarboxylase (ODC), a critical enzyme for liver regeneration, and polyamine levels in regenerating liver of 6-week-old and 1-year-old rats and (2) evaluated the effect of exogenous putrescine supplementation on liver regeneration in 1-year-old rats. ODC messenger ribonucleic acid (mRNA) transcript sizes were the same in rats of both ages.

Aging is associated with reduced liver regeneration and diminished thymidine kinase mRNA content and enzyme activity in the rat.

We studied the effect of aging on rat liver regeneration. We compared the time course of total hepatic mass, DNA and RNA accumulation, and thymidine kinase (TK) messenger RNA (mRNA) content and enzyme activity, after two-thirds partial hepatectomy in 6-week-old (young adult) and 1-year-old rats. Whereas 6-week-old rats had completely regenerated all liver mass, DNA, and RNA by 7 days, the regenerating 1-year-old rat livers at 7 days contained only 60% to 70% of the mass, DNA, and RNA in the normal 1-year-old rat liver.

Effects of partial and sham hepatectomy on ornithine decarboxylase and thymidine kinase activities and mRNA contents.

Ornithine decarboxylase and thymidine kinase are enzymes that increase in activity in regenerating liver. We found that both activities and mRNA levels for these enzymes increase significantly after 70% partial hepatectomy in the rat. After sham hepatectomy (laparotomy) there were significant decreases in activity; however, mRNA content was unaltered.

Ultrastructural study of hepatic regeneration following one-lobe, two-lobe, and subtotal hepatectomy in the rat.

The sequential and comparative ultrastructural features of regenerating rat liver following one-lobe, two-lobe, and subtotal hepatectomy were studied. All three groups demonstrated glycogen depletion at the 12 h post-hepatectomy interval with reaccumulation occurring at 24 h in the first two groups but not until 72 h in the subtotal hepatectomy group. Other hepatocellular alterations attributed to regenerative activity were similar in the three groups, however the onset and magnitude of those changes occurring in the two-lobe and subtotally hepatectomized rats differed significantly from those alterations occurring in the one-lobe hepatectomy group.