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At least 847 records · Page 47Linked to original sources
PubMed2006

Single dose of anti-transforming growth factor-beta1 monoclonal antibody enhances liver regeneration after partial hepatectomy in biliary-obstructed rats.

BACKGROUND: Transforming growth factor (TGF) beta is a potent inhibitor of hepatocyte DNA synthesis and liver regeneration. TGF-beta(1) expression progressively increases in obstructive jaundice. We investigated the effect of TGF-beta(1) blockage on liver regeneration in rats induced with obstructive jaundice. MATERIALS AND METHODS: Male Wistar-albino rats were divided into three groups: sham, control, and study groups. In the study and control groups, the common bile duct was ligated and divided, and 7 days later a partial hepatectomy was performed. In the study group, anti-TGF-beta(1) monoclonal antibody (10-microg single dose) was administered immediately after the 70% hepatectomy. In the control group, those rats in which obstructive jaundice was induced received normal saline after the 70% hepatectomy, and nonjaundiced rats received anti-TGF-beta(1) monoclonal antibody after the 70% hepatectomy. Rats were sacrificed after 48 or 72 h. Relative liver weight, AST, ALT, total and conjugated bilirubin, and TGF-beta(1) levels were measured. The mitotic index and proliferating cell nuclear antigen (PCNA) labeling index were evaluated as histopathologic parameters. RESULTS: At 72 h, the TGF-beta(1) level in the study group was similar to that in the sham group, whereas TGF-beta(1) in the study group was significantly lower than that of the jaundiced control group at 48 or 72 h (P < 0.001). The relative liver weight, mitotic index, and PCNA labeling index were significantly higher in the study group than in the jaundiced control group at 48 and 72 h (P < 0.001). The AST, ALT, and TGF-beta(1) levels were significantly higher in the jaundiced control group compared to the study group after 48 and 72 h, whereas these values were significantly lower in the nonjaundiced control group (P < 0.001). CONCLUSIONS: In obstructive jaundiced rats, TGF-beta(1) blockage with anti-TGF-beta(1) monoclonal antibody after liver resection improved liver regeneration both morphologically and functionally.

Alanine Transaminase↗
PubMedDate not supplied

Effects of streptococcal preparation OK-432 on liver regeneration and energy status after partial hepatectomy under ischemia/reperfusion in rats.

BACKGROUND/AIMS: Activation of reticuloendothelial system functions by the treatment with OK-432 has been reported to enhance liver regeneration. However, its effect on liver regeneration has not been studied after hepatectomy under ischemia/reperfusion which is in clinical use. The aim was to examine the effect of OK-432 on regeneration and energy status of the liver after hepatectomy under ischemia/reperfusion in rats. METHODOLOGY: Rats were randomly divided into two groups; OK-432 pretreatment and saline treatment (control) group. In the OK-432 group, OK-432 (2.5 mg/kg body weight) was administered intraperitoneally 24 hours before hepatectomy. In the control group, the same volume of physiological saline was administered in the same manner. Seventy percent hepatectomy was performed in both groups during the second 15-minute ischemia period after an initial 15-minute ischemia and 15-minute reperfusion periods. The survival after hepatectomy, relative liver weight, deoxyribonucleic acid synthesis rate, and hepatic adenine nucleotide and energy charge levels were examined immediately after hepatectomy and on postoperative days 1, 2, 3, and 7. Serum levels of total bilirubin, glutamic pyruvic transaminase, and hyaluronic acid were also measured. RESULTS: All rats survived and the relative liver weight and deoxyribonucleic acid synthesis rate were not significantly different in the two groups. Serum total bilirubin and glutamic pyruvic transaminase levels were not significantly different in both groups. The serum concentration of hyaluronic acid immediately after hepatectomy was significantly higher in the OK-432 group than in the control group. The pretreatment with OK-432 had no significant effect on the levels of adenine nucleotides and energy charge in the liver. CONCLUSIONS: Under ischemia/reperfusion, pretreatment with OK-432 has no significant effect on regeneration and energy status of the liver after hepatectomy.

Adenine Nucleotides↗
PubMed1999

Effects of glutamine administration on liver regeneration following hepatectomy.

The intestine is now known to be an important site of protein production in the body, and glutamine (GLN) stimulates both secreted and non-secreted protein synthesis in the small bowel. The purpose of the present study was to evaluate the effect of GLN-supplemented parenteral nutrition on liver regeneration after hepatectomy. Animals were divided into two groups: a sham-operated control group (Group A) and a 70%-hepatectomy group (Group B). Postoperatively, one-third of the animals in each group were maintained on intravenous 10% glucose solution, on 10% glucose with 2% standard amino acid solution, or 10% glucose supplemented with 2% glutamine for 24 h. GLN administration after hepatectomy significantly promoted liver regeneration. In addition, assessment of amino acid metabolism showed that GLN administration activated GLN metabolism in the intestine and promoted alanine uptake by the remnant liver. This metabolic response also enhanced both secreted and non-secreted protein synthesis in intestinal epithelial cells, especially in cells isolated from the crypts. The proteins produced are important as a portal production factor for liver regeneration and intestinal cell proliferation. Bacterial and endotoxin translocation, on the other hand, was significantly reduced. Thus, the results of this study suggest that intravenous administration of GLN after hepatectomy significantly promoted liver regeneration.

Amino Acids↗
PubMed1975

[Analysis of the kinetics of the transition of cells to DNA synthesis in systems with stimulated proliferation. III. Regenerating liver].

The application of the previously reported methods of kinetic analysis to cell proliferation studies in the regenerating rat liver is under consideration. A fraction of hepatocytes (nearly 60% of the initial hepatocyte number) synchronously entering the mitotic cycle in response to partial hepatectomy has been discovered. The investigation of the temporal pattern of the kinetic criterium qS (t) allowed to make a detailed description of the main features of the transition of hepatocytes to DNA synthesis during the first 40 hours of liver regeneration. Using kinetic criteria of the initial and repeated entry of cells into S-period made it possible to reveal that the prereplicative period in the second mitotic cycle was shorter than that in the first one. Thus, the hypothesis about a special period which is necessary for the quiescent cell to acquire the competence to proliferation is additionally supported.

Animals↗
PubMedDate not supplied

[Inhibition of growth of B16 melanoma caused by liver regeneration].

Phenomenon of spontaneous regression of cancer indicates that recovery from malignant disease can happen without the application of any so far known therapeutic treatment. The most of the self-cured patients have undergone surgical operation which did not eliminate entire tumor or did not affect malignant tissue at all. Furthermore, regression or reversion of tumors (transformation of tumor cells into normal, nonmalignant cells) can be achieved in plants or amphibia after exposure of tumor cells to the influence of normal, regenerating tissue. Thus, it seems that during tissue regeneration certain local changes in tissue happen (synthesis of some regulatory growth factors) which induce dying of tumor cells or modify main features of malignant cells. Previously we have studied growth of murine malignant tumors in regenerating tissue of liver and skin. Obtained results indicated that under the influence of regenerating tissue anaplasia of fibrosarcoma decreases, as well as do pigmentation and the incidence of live cells in melanoma B16 tissue. Thus, it is obvious that mechanism of regenerating tissue growth control, which can also change characteristics of tumor cells, exists in mammalia, too. In order to analyse whether the same homeostatic mechanism is responsible for the phenomenon of spontaneous regression of human cancer, we have analysed the growth of melanoma B16 in back limb of nonoperated and sham or partially hepatectomized mice. Regeneration of skin and abdominal wall tissue in sham hepatectomized animals slowed down tumor growth, while liver regeneration completely inhibited tumor progression. Tumor growth inhibition was result of tumor tissue necrosis which developed around blood vessels. However, the structure and integrity of blood vessels themselves was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Portal vein infusion of cancer chemotherapeutic agent emulsified with Lipiodol in regenerating liver after partial hepatectomy in rats.

Portal vein infusion of aclarubicin (ACR) emulsified with Lipiodol (LP) in regenerating liver after 70% partial hepatectomy in rats was evaluated for its safety and usefulness. DNA synthesis in regenerating liver was transiently suppressed by LP, ACR or LP+ACR, but no obvious inhibition was seen in aminopyrine N-demethylase activity and liver weights. LP significantly enhanced hepatic tissue levels of ACR and its active metabolites by long-term retention in the sinusoidal space. This study demonstrates that in rats LP has a powerful effect on the long-term retention of anticancer agents in the sinusoidal space after infusion into the portal vein, without aggravating hepatic damage by anticancer agents.

Aclarubicin↗
PubMed2002

Effects of portal vein arterialization on liver regeneration after partial hepatectomy in the rat.

Although portal venous supply is considered essential to preserve hepatic integrity, in this study, effects of portal arterialization on liver regeneration were evaluated in a rat model of partial hepatectomy (PH). Ninety-six Lewis rats were randomly assigned to four groups of 24 rats each: PH only (group 1), PH with either venous or arterialized portal supply (groups 2 and 3, respectively), and PH without portal supply (group 4). Liver regeneration rate (LRR), 5-bromo-2-deoxyuridine (BrdU) labeling index, and liver biological characteristics were assessed on days 1, 2, 3, and 7. Compared with group 1, all tested rats had a marked body weight loss after surgery, and only rats in group 4 showed no signs of recovery on day 7. With maintained portal inflow (groups 1, 2, and 3), LRRs increased steadily to day-7 values of 89.2% +/- 11.8%, 81.4% +/- 8%, and 77.4% +/- 9.4%, respectively (P = not significant), and 24-hour peak values of BrdU labeling index were 159 +/- 26, 157 +/- 42, and 149 +/- 48, respectively (P = not significant). Conversely, rats deprived of portal supply (group 4) showed profound inhibition of these two parameters (14 +/- 13; P <.01;32.1% +/- 7.7%; P <.001, respectively). These results indicate that proper portal blood supply is essential to initiate and maintain liver regeneration after PH. With an equivalent portal inflow rate of either venous or arterial source, the hepatic regeneration response can be sustained.

Animals↗
PubMed2003

Inhibitory effect of vitamin e administration on the progression of liver regeneration induced by partial hepatectomy in rats.

We have proposed that controlled peroxidative modifications of membranes could be playing a role in the early steps of liver regeneration. Hence, lipid peroxidation (LP) was modified in vivo by treatment with vitamin E in rats subjected to partial hepatectomy (PH), and its influence on liver regeneration was evaluated. Our results, using several methods to monitor LP, indicate that vitamin E administration promoted a decreased LP rate in liver subcellular membranes. Vitamin E drastically diminished cytosolic LP, shifting earlier increased LP in plasma membranes, and promoted a higher increase of nuclear LP in animals subjected to PH. Pretreatment with vitamin E induced a striking reduction of liver mass recovery and nuclear bromodeoxyuridine labeling (clearly shown at 24 hours after surgery), as well as promoted a decreased expression of cyclin D1 and of the proliferating cell nuclear antigen after PH. These effects seem to lead to a decreased mitotic index at 48 hours after PH. Vitamin E pretreatment also diminished PH-induced hypoglycemia but elevated serum bilirubin level, which was not observed in PH animals without vitamin treatment. In conclusion, an enhanced but controlled LP seems to play a critical role during the early phases of liver regeneration. Decreasing magnitude or time course of the PH-promoted enhanced LP (at early post-PH stages) by in vivo treatment with vitamin E could promote an early termination of preparative cell events, which lead to the replicative phase, during PH-promoted liver proliferation. The latter could have a significant implication in the antitumorigenic effect ascribed to the treatment with vitamin E.

Administration, Oral↗
PubMed1998

Transcriptional up-regulation of the delayed early gene HRS/SRp40 during liver regeneration. Interactions among YY1, GA-binding proteins, and mitogenic signals.

Arg-Ser-rich domain-containing proteins (SR proteins), a family of splicing factors, can regulate pre-mRNA alternative splicing in a concentration dependent manner. Thus, the relative expression of various SR proteins may play an important role in alternative splicing regulation. HRS/SRp40, an SR protein and delayed early gene in liver regeneration, can mediate alternative splicing of fibronectin mRNA. Here we determined that transcription of the HRS/SRp40 gene is induced about 5-fold during liver regeneration, similar to the level of steady-state mRNA. We found that both mouse and human HRS promoters lack TATA and CAAT boxes. The mouse promoter region from -130 to -18, which contains highly conserved GA-binding protein (GABP) and YY1 binding sites, conferred high transcriptional activity. While GABPalpha/GABPbeta heterodimer transactivated the HRS promoter, YY1 functioned as a repressor. During liver regeneration, the relative amount of GABPalpha/GABPbeta heterodimer increased 3-fold, and YY1 changed little, which could partially account for the increase in HRS gene transcription. Interleukin-6, a critical mitogenic component of liver regeneration, was able to relieve the repressive activity of the YY1 site within the HRS promoter. The combined effect of small changes in the level of existing transcription factors and mitogenic signals may explain the transcriptional activation of the HRS gene during cell growth.

Alternative Splicing↗
PubMed1971

Observations on liver regeneration after right hepatic lobectomy.

Restoration of liver mass has been studied in five patients after right hepatic lobectomy. The operation effects an approximate 50% resection of liver substance. Postmortem observations, measurements of the weight of liver resected at operation, and the study of serial radioisotopic liver scans suggest that liver regeneration in man is initiated very soon after partial hepatectomy and is well advanced within 10 days of operation.

Adolescent↗
PubMed1993

Early induction of LDL receptor gene during rat liver regeneration.

After partial hepatectomy in the rat, there is substantial lipid accumulation in the liver. No information is available on the possible role of receptor-mediated endocytosis in this process. Since the low density lipoprotein (LDL) receptor is stimulated as a part of an early growth response in cell culture (Ellsworth et al.: Biochem. J. 279:175-187, 1991), the metabolism of this receptor during liver regeneration was studied. The mRNA and membrane protein level of the receptor were measured in the liver and in the adrenal glands at different times after partial hepatectomy, corresponding to different phases of the cell cycle. A discontinuous pattern of receptor expression is detectable in the regenerating liver; a large increase of mRNA and membrane protein occurs at an early time (2-4 h), suggesting that there is induction of LDL receptor gene transcription shortly after partial hepatectomy. This response seems specific for the liver following injury since the adrenal receptor does not show a different pattern in partially hepatectomized rats and sham-operated controls. After returning to control levels, the LDL receptor again increases slightly above control at 24 h, a time when cell replication begins.

Adrenal Glands↗
PubMed1993

Gender-related differences in the inhibitory effect on liver regeneration in alcohol-treated rats: study of polyamine metabolism.

We studied gender-related differences in the effect of a single dose of ethanol (EtOH) on liver regeneration following partial hepatectomy in male and female rats by determining polyamines and their related enzymes. When rats were orally treated with EtOH at 3 g/kg 1 hr before partial hepatectomy, liver ornithine decarboxylase (ODC) activity at 4 hr post-hepatectomy was found to be lower in EtOH-treated female than male rats (51% vs. 42%, P < 0.01). Although no EtOH effect was observed on spermidine acetyltransferase (SAT) activity, female rats showed significantly higher values than male rats. Among intra-hepatic polyamines, putrescine was strongly affected by EtOH and significantly reduced in both male and female rats, but the effect was more marked in female than in male rats (88% vs. 51%, P < 0.01). With respect to spermidine and spermine, male rats were unaffected by EtOH, whereas EtOH-treated female rats had lower levels. The gender-related differences became more distinct in terms of total polyamine; the decrease in total polyamine due to EtOH was observed in female rats only. These results suggested that there was a gender-related difference in the effect of EtOH on liver regeneration after partial hepatectomy, with the variations in polyamines probably affecting the subsequent process of liver regeneration.

Acetyltransferases↗
PubMed1999

[3H]thymidine incorporation into whole liver as an alternative to [3H]thymidine incorporation into DNA as a parameter of cell proliferation in regenerating liver tissue in rats.

OBJECTIVE: To monitor liver regeneration following partial hepatectomy, liver cell proliferation can be measured by assaying in vivo [3H]thymidine incorporation into liver cell DNA. We hypothesized that [3H]thymidine incorporation into whole liver tissue parallels [3H]thymidine incorporation into liver cell DNA, both in high proliferating and low proliferating liver. STUDY DESIGN: Liver cell proliferation in rats after partial hepatectomy or a sham operation was studied by measuring incorporation of [3H]thymidine into various fractions of liver tissue on days 1, 2, 3, 4 and 10 after surgery. RESULTS: [3H]thymidine incorporation into whole liver tissue and in the protein fraction correlated well with DNA-specific [3H]thymidine incorporation into regenerating (r > .80, P < .0001) and nonregenerating liver (r > .69, P < .005). [3H]thymidine incorporation into DNA was < 5% of the total amount of administered [3H]thymidine in both sham-operated and hepatectomized rats. Significant differences in [3H]thymidine incorporation into partially hepatectomized livers as compared to sham-operated rat livers were found on days 1 and 2 (whole liver tissue and protein fraction) or day 1 (DNA) after surgery. CONCLUSION: [3H]thymidine incorporation into whole liver tissue is a simple technique that can be used for the study of liver cell proliferation after partial hepatectomy in rats.

Animals↗
PubMed2004

Subtotal hepatectomy: a porcine model for the study of liver regeneration.

BACKGROUND: This study aimed to devise a simple, reproducible method of subtotal hepatectomy in a large animal model. Such an experimental model could be useful in the investigation of liver regeneration and liver insufficiency after partial hepatectomy. Equally, this technique could be used for assessing the effect of artificial liver support systems on both liver function and regeneration. MATERIALS AND METHODS: Twenty pigs were subjected to either 70-80% liver resection (n = 11), or 85-90% liver resection (n = 9), using a simplified technique. RESULTS: Most tolerated the procedure well and showed restoration of full liver volume within 3 weeks. Three animals in the 90% resection group died with significantly raised levels of International Normalized Ratio (INR) and ammonia. CONCLUSIONS: These two techniques have been shown to be easily reproducible and well tolerated by the animals and allow easy assessment of liver function and regeneration in the postoperative period. The deaths in the 90% resection group supports the hypothesis that 90% partial hepatectomy represents a model of critical residual liver parenchyma.

Animals↗
PubMed1987

[Efficacy of vagotomy on liver regeneration in the prevention of stress ulcer after partial hepatectomy in the cirrhotic rat].

Possible effects of vagotomy (a means of preventing stress ulcers after partial hepatectomy in cirrhotic liver) on liver regeneration were explored. Cirrhosis was induced in rats by means of intraperitoneally administering 4% thioacetamide for 10 consecutive weeks. These rats were subjected to partial hepatectomy (ca. 68% resection) and vagotomy at the same time. Normal rats of consistent age served as controls after receiving hepatectomy. In controls, which received hepatectomy alone, both gastric pH and gastric wall blood flow showed a significant reduction on the third day after surgery. In animals which received both hepatectomy and vagotomy, postoperative reduction in gastric pH was suppressed, but postoperative reduction in gastric wall blood flow was more marked compared to those of controls. In animals which received both hepatectomy and vagotomy, postoperative 3H-thymidine intake and thymidine kinase activity were markedly suppressed compared to controls. In animals which received both hepatectomy and vagotomy, the peak level of mitotic index and the hepatic regeneration rate were markedly suppressed compared to those of controls. The above results indicate that vagotomy is not advantageous to liver regeneration and prevention of stress ulcer after partial hepatectomy in cirrhotic rat because of its potency of inducing marked reduction in gastric wall blood flow and impediment of liver regeneration.

Animals↗
PubMed2003

Role of Valpha 14 NKT cells in the development of impaired liver regeneration in vivo.

Although we have previously demonstrated that IL-12 stimulation increases the number of hepatic natural killer (NK) T (NKT) cells and enhances liver injury during the early phase of liver regeneration, the role of NKT cells has remained unknown. We therefore evaluated the influence of NKT cells activated by IL-12 or by alpha-galactosylceramide (alpha-GalCer) on murine liver regeneration using Valpha 14 NKT knockout (Jalpha 281(-/-)) mice. Levels of serum alanine aminotransferase (sALT) 24 hours after partial hepatectomy were enhanced in Jalpha 281(+/+) but not in Jalpha 281(-/-) mice by both procedures. Hepatic NKT cells expressed considerably more interferon (IFN) gamma and tumor necrosis factor alpha (TNF-alpha) messenger RNA (mRNA) after stimulation with both factors in Jalpha 281(+/+) mice. Either anti-IFN-gamma or TNF-alpha antibody inhibited the enhancement of liver injury. Furthermore, recombinant TNF-alpha injection similarly caused injury in hepatectomized livers of both Jalpha 281(+/+) and Jalpha 281(-/-) mice; indeed, adoptively transferred TNF-alpha(+/+) NKT cells enhanced liver injury after hepatectomy in TNF-alpha knockout mice. TNF receptor expressions on hepatocytes increased and peaked 24 hours after partial hepatectomy. In conclusion, simultaneous TNF-alpha synthesis and high levels of TNF receptor expression on hepatocytes cause severe liver damage by activated NKT cells during liver regeneration.

Animals↗
PubMed1984

[Capacity of intact and regenerating liver to trap CFUs].

The normal and regenerating mouse liver is capable of trapping transplanted bone marrow CFUs, with this capability being increased in the regenerating liver. Inactivation of macrophages (Kupffer cells) by silica particles sharply reduces this ability, thus pointing to direct or indirect involvement of macrophages into the trapping of exogenous CFUs.

Animals↗