Regenerating Liver Tissue Research Articles

Late phase of liver restoration following partial hepatectomy in phenobarbital-treated rats. I. Effect of preoperative and postoperative phenobarbital treatment on organ weight, protein and DNA content of the normal and the regenerating liver.

Rats were treated with phenobarbital (50 mg/kg) for 7 days prior to or after partial hepatectomy. Liver weight, protein, DNA, and RNA content were determined in liver tissue removed at operation as well as in regenerating liver 7 days later at the time of death. When rats were treated with phenobarbital in the preoperative period an increase in liver weight secondary to cell hyperplasia was observed as compared to livers of rats treated with sodium chloride. The weight of regenerating liver of preoperatively treated rats did not differ from the controls, but protein concentration was significantly higher (P less than or equal to 0.001). When phenobarbital was applied only in the postoperative period, a highly significant (P less than or equal to 0.001) enlargement of the regenerating liver tissue was found secondary to cell hypertrophy without hyperplasia, whereas protein concentration was unchanged. An increased RNA/DNA ratio, however, suggests that further protein synthesis is enhanced. The results show that both preoperative and postoperative phenobarbital treatment aids in hepatic tissue enlargement, though by a different mechanism.

Lipid metabolism in partially hepatectomized dogs and effect of hepatic periarterial neurectomy.

Lipid metabolism in partially hepatectomized dogs was studied, by observing changes in serum lipids after hepatectomy and biosynthesis of lipids in the slices of the regenerating liver tissue. In addition, the effect of hepatic periarterial neurectomy was evaluated. Serum lipids decreased after partial hepatectomy and did not return to the postoperative level until the first postoperative week, whereas biosynthesis of lipids in the slices of the regenerating liver tissue was considerably augmented in the early postoperative period. This augmentation of lipid synthesis appears to be requirement for regeneration of the liver. When hepatic periarterial neurectomy plus partial hepatectomy was carried out, each lipid and lipoprotein fraction, except for FFA, showed a tendency to recovery earlier from the immediate postoperative decrease and did not show a late postoperative excessive increase. The decrease of alpha-lipoprotein in the immediate postoperative period was augmented and the time of the peak of concentration of pre-beta-lipoprotein was hastened. Therefore, hepatic periarterial neurectomy seems to act in such a manner so as to maintain the homeostasis in lipid metabolism after partial hepatectomy and to activate the regenerative property of the residual liver in the early postoperative period.

Synthesis in vitro of glycosaminoglycans in regenerating rat liver.

Chronic liver damage is accompanied by both liver cell multiplication and stimulated synthesis of proteoglycans, but the relationship between the two biochemical processes has not been investigated so far. We found that the incorporation of [14C]glucosamine into total glycosaminoglycans of rat liver slices from regenerating tissue is depressed by about 50% 1 and 3 days after operation if referred to that measured in sham-operated control liver slices. 6 h after partial hepatectomy [14C]glucosamine incorporation into glycosaminoglycans is stimulated by more than 30% in relation to sham operated livers. The proportional rates of synthesis of heparan sulfate and chondroitin sulfate (about 8:1) did not change in regenerating liver tissue. Furthermore, there was no difference in the intracellular uptake of [14C]glucosamine by rat liver slices from sham operated and partially hepatectomized rats; the pool size of UDP-N-acetylhexosamine was only slightly larger (about 14%) under the latter experimental condition. We conclude that liver regeneration by itself is not responsible for the elevated production and the changing pattern of proteoglycans in long-lasting hepatic injury.

Changes in Transcription of Endogenous Type-C Virus Genome During Mouse Liver Regeneration

In the present study the extent of endogenous, type-C virus genome transcription in normal and regenerating mouse liver was analysed by using the technique of nucleic acid hybridization. The RNA preparations from regenerating liver tissues collected at various intervals following partial hepatectomy, and from normal liver samples of BALB/c mice, were hybridized to 3H-DNA complementary to 60 to 70S RNA of an endogenous, N-tropic virus, released spontaneously from BALB/c mouse cells in culture. Although partial transcription of the endogenous virus genome can be clearly detected in normal liver, a significant increase in the level of virus-specific RNA synthesis in the regenerating liver, in comparison to normal liver, is apparent, following partial hepatectomy. This increase in virus-specific RNA synthesis attains its highest level just before the level of DNA synthesis in the regenerating liver reaches its maximum. These observations may indicate a qualitative or quantitative change in the endogenous type-C virus genome transcription pattern in hepatocytes, in response to partial hepatectomy and suggest that this change in the transcription pattern and the initiation of cell proliferation, in regenerating livers, are probably sequential and related events.

A connection between the production of prostaglandins during liver regeneration and the DNA synthetic response

The concentration of PGE equivalents in rat liver in vivo was increased during liver regeneration. The probability that this increase reflected a stimulation of prostaglandin synthesis was confirmed in vitro by the ability of homogenates of regenerating liver tissue to synthesize PGE 2 and PGF 2α from arachidonate. Indomethacin prevented these prostaglandin changes, and the subsequent increase in DNA synthesis. The administration of indomethacin to rats was found to induce a hypocalcemia, and to block the hypercalcemic action of parathyroid hormone. It is suggested that the influence of prostaglandins on DNA synthesis involves calcium metabolism.

Genetically determined resistance to infection by hepatotropic influenza A virus in mice: effect of immunosuppression

Mice carrying the gene Mx were resistant to the lethal action of a hepatotropic line of avian influenza A virus. In resistant animals, foci of liver necrosis were self-limiting, and maximal virus titers reached were much below those in susceptible animals. Resistance could not be abrogated by immunosuppressive treatment with cyclophosphamide, methotrexate, or procarbazine, although such treatment prevented cellular infiltration at sites of virus replication and appeared to delay virus clearance. Silica and thorium dioxide, thought to inhibit macrophage function, likewise failed to abolish resistance. Regenerating liver tissue did not support more extensive virus replication than did intact adult liver.

Formation of colonies in soft agar medium by regenerating liver cells (38591).

The culture of actively regenerating liver tissue in soft agar reveals the presence of a cell population, not previously described, which includes (a) cells capable of forming hematopoietic colonies and (b) additional cells producing colonies with epithelioid characteristics.

2696. Nitrosamine susceptibility of regenerating liver tissue: Pound, A. W., Lawson, T. A. & Horn, Lorraine (1973). Increased carcinogenic action of dimethylnitrosamine after prior administration of carbon tetrachloride. Br. J. Cancer27, 451

2696. Nitrosamine susceptibility of regenerating liver tissue: Pound, A. W., Lawson, T. A. & Horn, Lorraine (1973). Increased carcinogenic action of dimethylnitrosamine after prior administration of carbon tetrachloride. Br. J. Cancer27, 451

Ultrasonic Reduction of Mitotic Activity in Regenerating Rat Liver

In the adult rat liver there is ordinarily little cell division, but in response to an urgent demand for cells (as occurs after partial liver removal) large numbers of cells divide. The purpose of this study was to measure levels of mitotic activity (stimulated by partial hepatectomy) after ultrasonic treatment of the intact liver. Anesthetized male Charles River rats were treated with ultrasound and their mitotic indices compared with control animals. A continuous 2-MHz 100-mW/cm2 unfocused sound beam was oriented to impinge on the liver. The transducer was placed on the abdomen for a treatment time of five minutes. Temperature rises were less than 5°C at the transducer-abdomen junction and less than 1°C in the liver. Within two hours of treatment about 70% of the liver was surgically removed. Twenty-eight to 30 hours after partial hepatectomy (the time of peak mitotic activity in control animals) the mitotic index of the regenerating liver tissue was observed. Treated animals showed a reduction in mitotic index to about one-half that for controls. Statistical analysis showed the results to be significant at the 1% level. [This work was supported in part by grants from R. J. Reynolds Industries, Inc., and the USPHS, Food and Drug Administration, Grant RL-00129.]

EFFECT OF ADRENOCORTICOTROPHIC HORMONE AND CORTISONE ON THE UPTAKE OF TRITIATED THYMIDINE BY REGENERATING LIVER TISSUE IN THE WHITE RAT.

THERE have been many reports concerning the relations between nucleic acid metabolism and adrenocortical hormones. But there are only a few data concerning the mechanism by which the adrenal glucocorticoid hormones (and ACTH) influence mitosis1. Cortisone has been found to lessen hepatic regeneration2, probably through an antimitotic action on regenerating liver3. It has also been demonstrated that ACTH, cortisone and dehydrocortisone inhibit the formation of granulation tissue4,5. However, the mechanism by which corticoids influence the metabolism of proteins4 and that of the nucleic acids is not yet known.

Oxidative phosphorylation and amino acid incorporation into protein in regenerating rat liver.

SummaryIn slices from regenerating rat liver 84 and 168 hours after hepatectomy, oxygen consumption is moderately increased and glycine-1-C14, L-leucine-C14 and L-phenylalanine-C14 incorporation into protein is markedly increased as compared with normal liver slices. On the other hand, in liver homogenates, incubated with succinate or α-ketoglutarate as substrates, oxidative phosphorylation is decreased in the early stages (84 hours) of regeneration. The results suggest the following conclusions: 1) in regenerating liver tissue, amino acid incorporation into protein can increase even without a parallel increase in the aerobic formation of high energy phosphates; 2) in both normal and regenerating rat liver, the availability of ~ P greatly exceeds that needed for protein synthesis.

Rhodanese Activity of Resting, Regenerating, and Neoplastic Liver Tissue of the Rat<xref ref-type="fn" rid="fn1">1</xref>, <xref ref-type="fn" rid="fn2">2</xref>

Rhodanese Activity of Resting, Regenerating, and Neoplastic Liver Tissue of the Rat<xref ref-type="fn" rid="fn1">1</xref>, <xref ref-type="fn" rid="fn2">2</xref>