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At least 811 records · Page 45Linked to original sources
PubMed2002

Halofuginone, a collagen type I inhibitor improves liver regeneration in cirrhotic rats.

BACKGROUND/AIMS: Hepatic fibrosis involves excess deposition of extracellular connective tissue of which collagen type I fibers form the predominant component. Left untreated it develops into cirrhosis, often linked with hepatocellular carcinoma. Owing to the fact that cirrhotic liver regeneration is impaired, resection of hepatocellular carcinoma associated with cirrhosis is questionable. The aim of the present study was to determine the potential of halofuginone, a collagen type I inhibitor, in improving liver regeneration in cirrhotic rats. METHODS: Partial hepatectomy (70%) was performed in thioacetamide-induced cirrhotic rats fed a halofuginone-containing diet. Liver regeneration was monitored by mass and proliferating cell nuclear antigen. The Ishak staging system and hydroxyproline content were used to evaluate the level of fibrosis. RESULTS: Halofuginone administered prior to and following partial hepatectomy did not inhibit normal liver regeneration despite the reduced levels of collagen type I mRNA. When given to rats with established fibrosis, it caused a significant reduction in alpha smooth muscle actin, TIMP-2, collagen type I gene expression and collagen deposition. Such animals demonstrated improved capacity for regeneration. CONCLUSIONS: Halofuginone may prove useful in improving survival of patients with hepatocellular carcinoma and cirrhosis undergoing surgical resection.

Animals↗
PubMed2005

Enhancement of liver regeneration by the association of Hyptis pectinata with laser therapy.

Since new molecules that normally would accelerate regeneration can also be potentialized by light, the use of new substances combined with laser therapy seems to be a natural type of experiment. Therefore, the purpose of this study was to assess the effects of Hyptis pectinata leaves on liver regeneration after partial hepatectomy (PH) associated with laser therapy. Twenty-four rats were divided into four groups--PH(control), PHL (laser therapy), PH200 (200 mg/kg of Hyptispectinata), and PHL200 (200 mg/kg of the plant and laser)--which were submitted to 67% hepatectomy. Laser treatment consisted of focusing the light on the remaining liver after hepatectomy. The data analyzed were serum levels of aminotransferases, liver regeneration, and mitochondrial function. Group PH200 showed a statistically significant decrease in AST levels, and PHL200 disclosed an augmentation in ALT levels. The liver regeneration index was significantly increased in group PHL200. Concerning liver mitochondrial respiratory assay, groups PH200 and PHL200 showed lower state 3 levels than groups PH and PHL. Group PHL showed an increase in state 4 levels and a reduction in membrane potential and RCR. The present study shows that the association of the aqueous extract of Hyptis pectinata leaves at 200 mg/kg with intraoperative laser therapy can stimulate liver regeneration and cause a reduction in liver mitochondrial respiratory function without altering its phosphorylative activity.

Animals↗
PubMed1993

[Liver regeneration in man. A prospective CT-volumetric study].

To get reliable data on human liver regeneration we performed CT volumetry in 25 patients who underwent partial hepatectomy for benign and malignant liver tumours preoperatively and at least one year postoperatively in regular intervals in a prospective study. All patients received standardised CT-scans preoperatively and two weeks, 3, 6 and 12 months post-operatively. The resected specimen size was determined by water displacement. We were able to demonstrate human liver regeneration. Contrary to the well-known animal model the amount of regeneration in humans is less and regeneration takes a longer time. We did not find any statistical correlation to extent of resection, age of patients and other parameters. On the contrary, the human liver seems to regenerate until a certain relationship of liver volume and body-surface area is reached: 0.8 l/m2.

Adult↗
PubMed2000

Expression of inhibin betaA, betaB and follistatin mRNAs in the carbon tetrachloride induced rat liver regeneration model.

Follistatin (FS, an activin-binding protein) and activin A (homodimer of inhibin betaA chain) promote and inhibit cell proliferation in rat liver, respectively. The roles of activin AB (heterodimer of inhibin betaA and betaB) and activin B (homodimer of inhibin betaB) in rat liver have not been elucidated yet. In this study, we examined, by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, whether the levels of FS, inhibin betaA and betaB mRNAs change in the carbon tetrachloride induced rat liver regeneration model. The analysis was made in an hour-by-hour manner during the early stage of liver injury. There are 2 types of FS mRNA, FS-288 and FS-315, and the levels of both had begun to increase at 3 h, were maximal at 6 h, remained constant up to 12 h, and thereafter gradually decreased. The inhibin betaA mRNA had started to decline at 3 h, reached its lowest level at 6 h, partly returned at 12 h, and remained constant up to 48 h. The inhibin betaB mRNA level had begun to increase at 1 h, was maximal at 3 h, remained constant up to 24 h, and returned to the original level at 48 h. These results indicate that FS and activin A may act reciprocally in liver regeneration, and also suggest that activin AB and B may play roles in liver regeneration that differ from that of activin A.

Animals↗
PubMed1998

[Effect of glucagon and insulin administration on the inhibition of rat liver regeneration by acute ethanol treatment after partial hepatectomy].

We studied the effects of glucagon and insulin (GI) administration on the inhibition of liver regeneration by acute ethanol treatment after partial hepatectomy (PH) in rats. When ethanol was given 1 hour before PH at 3 gm/kg body wt., [3H] thymidine incorporation into the hepatic DNA 24 hr after PH was significantly inhibited, but it was completely reversed by GI treatment. Although hepatic ornithine decarboxylase (ODC) activity in the ethanol-treated group 4 hr after PH was significantly inhibited, it was completely reversed by GI treatment. The putrescine (PUT) level in the liver 4 hr after PH was decreased by ethanol, but it was increased by GI treatment. At 12 hr after PH, ODC activity was not inhibited and PUT level in the liver was not decreased by ethanol. The levels of spermidine and spermine in the liver 4 hr after PH were unaffected either by ethanol or by GI treatment. Spermidine/spermine-N1 acetyltransferase activity in the liver 4 hr after PH was showed a tendency to increase by ethanol but it was decreased by GI treatment. Difluoromethylornithine, a specific inhibitor of ODC, decreased the level of PUT in the liver, and inhibited [3H] thymidine incorporation. The intraperitotneal administration of PUT significantly increased [3H] thymidine incorporation. The increase in ODC mRNA caused by pH was inhibited by ethanol, but it was completely reversed by GI treatment. SAT mRNA was affected neither by ethanol ner GI treatment. These results suggested that GI treatment was effective on the inhibition of liver regeneration by acute ethanol treatment, and activation of liver regeneration by GI treatment is closely related with ODC induction at the level of transcription.

Animals↗
PubMed2000

Gadolinium pretreatment decreases survival and impairs liver regeneration after partial hepatectomy under ischemia/reperfusion in rats.

BACKGROUND: Modulation of Kupffer cell functions by treatment with gadolinium chloride protects the liver against reperfusion injury. However, its effect on liver regeneration after hepatectomy under ischemia/reperfusion has not been studied. Using a common clinical ischemia/reperfusion technique, we examined the effect of gadolinium on liver regeneration after hepatectomy in rats. METHODS: After an initial 15-minute ischemia and 15-minute reperfusion, 70% hepatectomy was performed during the second 15-minute ischemia period in gadolinium-pretreated (gadolinium group) and saline solution--pretreated (control group) rats. The 24-hour survival rate, relative liver weight, DNA synthesis rate, and hepatic adenosine triphosphate level were examined immediately after hepatectomy and on postoperative days (PODs) 1, 2, 3, and 7. Serum levels of total bilirubin, glutamic pyruvic transaminase, and endotoxin were also measured. RESULTS: The 24-hour survival rate was significantly lower in the gadolinium group (67%) than in the control group (100%). On POD 1, the relative liver weight and DNA synthesis rate were significantly lower in the gadolinium group than in the control group. On POD 1, serum total bilirubin and endotoxin levels were significantly higher in the gadolinium group than in the control group. Immediately after hepatectomy, the hepatic adenosine triphosphate level was significantly lower in the gadolinium group than in the control group. CONCLUSIONS: Under ischemia/reperfusion, gadolinium pretreatment impairs liver regeneration and energy status after hepatectomy and decreases postoperative survival.

Adenosine Triphosphate↗
PubMedDate not supplied

The impact of transient elevation of intra-abdominal pressure on liver regeneration in the rat.

Transient increased intra-abdominal pressure (IIAP) due to carbon dioxide insufflation is suspected to cause a form of ischemia-reperfusion injury. Considering this, a study was designed to assess the effect of transient IIAP on liver regeneration in a rat model. Six groups of animals (each n = 6) were studied. While experiments in Group 1 (IIAP+PHR) were subjected to IIAP, following partial hepatic resection (PHR), those in Group 2 (IIAP) experiments were subjected to IIAP. Animals in Group 3 (IR+PHR) were subjected to liver ischemia-reperfusion (IR) following PHR, and those in Group 4 (IR) underwent only IR. Group 5 (PHR) and Group 6 (healthy) served as controls. Blood was taken for assessment of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 with enzyme-linked immunosorbent assay (ELISA) at day 5 postoperatively. Each rat was then given a lethal injection of pentobarbital. Gravimetric analysis and immunohistochemistry staining for proliferating cell nuclear antigen (PCNA) were used for assessments of liver regeneration. Apoptosis was assessed by immunohistochemical TUNEL index, expressed as the number of positive cells/per total number of cells at the same time. Although mean liver regeneration rates of Group 1 and Group 3 were the same, that of Group 5 was the highest (p = .04). Serum TNF-alpha levels of Group 1 versus Group 3 were 340 pg/ml versus 352 pg/ml. Serum IL-l levels of Group 1 versus Group 3 were 124 pg/ml versus 135 pg/ml. Serum TNl-alpha and IL-6 levels of Group 1 and Group 3 were the same at the first day of surgical procedure (p > .05). Mean serum TNF-alpha levels of Group 5 (387 pg/ml) were significantly higher than those of both Group 1 and Group 3 at 24 h of operation. Serum IL-6 levels of Group 5 (174 pg/ml) at the same time was higher than those of Group 1 and Group 3 at the same time (p = .01). Proliferating cell nuclear antigen indices of Group 1, Group 2, Group 3, Group 4, and Group 6 were the same; however, the mean PCNA-labeling index of Group 5 was higher than those of the others. There were no significant differences between the groups (p > .05). Liver regeneration is suppressed by transient IIAP. However, the effect of IIAP on liver apoptosis needs to be clarified.

Abdomen↗
PubMed1978

Transcription of the non-repetitive genome in liver hypertrophy and the homology between nuclear RNA of normal and 12 H-regenerating liver.

The percentage of the non-repetitive genome transcribed and the complexity of nuclear RNA were estimated in normal and 12 h-regenerating rat liver. Nuclear RNA from normal or 12 h-regenerating liver hybridizes with approximately 6.1% of non-repetitive DNA (12.2% of the single-copy genome, assuming assymetric transcription). The estimated complexity of either of these nuclear RNA populations is 7.6 . 10(10) daltons, which is approximately 7 times higher than that calculated for polysomal mRNA. Cross hybridization experiments did not show differences between the nuclear RNA populations of normal and 12 h-regenerating liver. The results indicate that liver hypertropy (without hyperplasia) may be brought about without a large increase in the proportion of the non-repetitive genome transcribed.

Animals↗
PubMed2006

Liver regeneration and hemodynamics in pigs with mesocaval shunt.

BACKGROUND: A surgical technique using a mesocaval shunt and downstream ligation of the superior mesenteric vein has been recently proposed to overcome the size limitations that restrict the use of partial liver grafts. We designed an experimental study in pigs to evaluate the capacities of liver regeneration and hemodynamic changes after completion of this procedure. MATERIAL AND METHODS: Liver regeneration after left hepatectomy was compared between two groups of five pigs, with or without mesocaval shunt, sacrificed 11 to 14 days after surgery. A third group of five animals was used for hemodynamic studies. RESULTS: Liver regeneration in study animals was 45.3% of controls. This was obtained despite a reduction of the venous inflow to 15.6% of the control, resulting in a net decrease of the total blood inflow to 56% of the control, despite a compensatory increase in the arterial inflow. There was no significant difference in mitotic index, hepatocellular size, and glycogen content between study and control animals. CONCLUSION: Our experimental study confirms that the regenerative capacities of the pig liver are largely preserved despite the dramatic reduction of the venous blood inflow, reduced to its gastroduodenosplenopancreatic component. This lends further support to the hypothesis that the gastroduodenosplenopancreatic blood is enriched in hepatotrophic factors, likely to originate from the pancreas and duodenum.

Anastomosis, Surgical↗
PubMed1998

Hepatocyte growth factor promotes liver regeneration with prompt improvement of hyperbilirubinemia in hepatectomized cholestatic rats.

BACKGROUND: In hepatectomy for patients with liver cirrhosis or cholestasis, prolonged postoperative hyperbilirubinemia is a troublesome complication and, if uncontrolled, often leads to life-threatening hepatic failure. Hepatocyte growth factor (HGF), first identified as the most potent mitogen for primary hepatocytes, has been shown to have multiple biological properties on liver, including mitogenic, antifibrotic, and cytoprotective activities. This study investigated the beneficial effects of a perioperative HGF supply to jaundiced liver after hepatectomy in rats. MATERIALS AND METHODS: As a model of jaundiced liver, we used an alpha-naphtylisocyocyanate (ANIT)-induced intrahepatic cholestasis model. Forty-eight hours after intraperitoneal injection of ANIT (75 mg/kg), when the total serum bilirubin level was moderately increased, a 70 % hepatectomy was performed. Human recombinant HGF (250 microgram/kg) (n = 15) or vehicle alone (n = 15) was intermittently administered to the rats 12 h before surgery and every 12 h after that until sacrifice. RESULTS: Perioperative HGF treatment effectively accelerated hepatocellular DNA synthesis of cholestatic liver followed by increase in the regenerated liver weight. Moreover, HGF supply promptly improved hyperbilirubinemia within 24 h after surgery. Histological examination revealed that HGF administration attenuated periportal inflammation and formation of bile duct obstructions. Postoperative serum concentrations of tumor necrosis factor-alpha, a representative inflammatory cytokine, were not altered by HGF treatment. CONCLUSIONS: Perioperative HGF supply not only promotes liver regeneration but also ameliorates hyperbilirubinemia in hepatectomized cholestatic rats. This mode of HGF treatment may be clinically useful for hepatectomy in patients with cholestasis.

Animals↗
PubMed1993

Hepatic branch vagotomy can suppress liver regeneration in partially hepatectomized rats.

The role of the vagus nerve in liver regeneration after partial hepatectomy was studied by comparing the effects of hepatic branch vagotomy with those of hepatic branch sympathectomy in rats. The liver weight as a percentage of body weight decreased significantly 7 days after vagotomy compared with the controls and this was associated with a reduction in food intake. There was no difference in the liver weights between the control rats and the pair-fed vagotomized rats. Hepatic sympathectomy had no significant effect on the liver weight. The serum scores indicating hepatic function showed no difference between the control and the vagotomized rats except alkaline phosphatase. The concentration of insulin was unchanged. The number of mitotic hepatocytes remained high at 7 days after vagotomy. These observations led us to conclude that the vagus nerve stimulates liver regeneration, and its effect depends on vagal factors directly and specifically.

Alanine Transaminase↗
PubMed1998

alpha-Fetoprotein gene sequences mediating Afr2 regulation during liver regeneration.

alpha-fetoprotein (AFP) gene expression occurs in the yolk sac, in the fetal liver and gut, and in the adult liver during regeneration and tumorigenesis. Two unlinked genes determine the level of AFP gene expression in adult mice: Afr1 regulates the basal level of expression in the normal adult liver, and Afr2 regulates the increase in expression during liver regeneration. It has been shown that AFP-derived transgenes, including the sequences between -1,010 and -838 bp and between -118 bp and the transcriptional start site were induced appropriately during liver regeneration and were Afr2-regulated. To assess the role of the distal sequence in gene expression during liver regeneration, a new transgene with 7.6 kilobases of 5'-flanking sequence deleted between -1,010 and -838 bp was designed. We show that this transgene was subject to characteristic AFP tissue-specific and developmental regulation, in that it was highly expressed in the yolk sac and the fetal liver and gut but not in normal adult tissues. Expression was induced in response to liver regeneration as observed for the endogenous gene. The genetic regulation of the basal level of AFP gene expression in adult liver by the Afr1 gene was undisturbed. However, transgene expression was not regulated by Afr2 during liver regeneration. Our data suggest that Afr2 regulation of AFP gene expression during liver regeneration requires the sequence between -1,010 and -838 bp and is independent of other regulatory mechanisms.

Animals↗
PubMed1980

[Age dependence of the median duration of the mitotic cycle and the time for duplication of the hepatocyte number in ontogeny and in liver regeneration].

A mathematical intepretation is given for the published data on the kinetics of proliferation of the hepatocytes during ontogenesis and liver regeneration. The equations were obtained which described the age dependence of the mitotic cycle duration, the time of the cell number was found prior to the sexual maturation of the animals; the minimal and regeneration; a "break" of the curve describing the change of the time of duplication of the cell number was found prior to the sexual maturation of the animals; the minimal duration of the mitotic cycle and the time of duplication of the cell number during ontogenesis and liver regeneration was estimated; the age of animals was established at which the mitotic cycle of hepatocytes had the same duration as at the definite stage of liver regeneration.

Aging↗
PubMed1979

Sister chromatid exchange in murine alveolar macrophages, regenerating liver and bone marrow cells--a simultaneous multicellular in vivo assay.

Differential labeling of sister chromatids was achieved simultaneously in murine alveolar macrophages, regenerating liver, and bone marrow cells of partially hepatectomized mice as well as in alveolar macrophages and bone marrow cells of nonhepatectomized mice. The mean frequency of SCE/cell +/-S.D. and the percentage of second division cells for each cell type were determined. No significant differences in mean frequencies of SCE/cell were observed among the cell types or between hepatectomized (alveolar macrophages--3.6+/-2.2, bone marrow--3.4+/-2.2; regenerating liver--3.6+/-2.4) and nonhepatectomized (alveolar macrophages--3.4+/-1.9; bone marrow--2.9+/-1.8). Although the percentage of second division cells was dependent upon cell type, no significant differences were apparent between hepatectomized (alveolar macrophages--57+/-8%; bone marrow--37+/-6%; regenerating liver--65+/-6%) and nonhepatectomized mice )alveolar macrophages--53+/-6%; bone marrow--36+/-4%). Comparisons between BrdU treated and nontreated nonhepatectomized mice revealed no significant alteration in mitotic yields.

Animals↗
PubMed1964

A FINE STRUCTURE STUDY OF LIPID IN MOUSE LIVER REGENERATING AFTER PARTIAL HEPATECTOMY.

The fine structure of liver 3(1/2) to 72 hours after partial hepatectomy has been compared with that of liver from sham-operated animals; all animals were 60- to 90-day old male mice of the C3H strain. Numerous small bodies with diameters ranging from 300 to 1,000 A have been observed distributed randomly throughout the cytoplasm of the hepatic parenchymal cells at early intervals after partial hepatectomy. In material fixed in osmium tetroxide and embedded in methacrylate, they appear as uniformly electron-opaque bodies, but in permanganate-fixed liver, they display only a peripheral rim of electron-opaque material surrounding a clear core. Each of these cytoplasmic bodies appears to be located within a vesicle. A few of the opaque bodies are also present in sinusoids and in the spaces of Disse; these bodies are not located within vesicular structures. Fat droplets of various sizes are easily distinguished in regenerating liver; with the increase in number of these fat droplets at later postoperative intervals, there occurs a concomitant decrease in the number of cytoplasmic bodies. It is suggested that the cytoplasmic bodies contain some lipid component. Possible explanations of the origin, nature, and fate of the cytoplasmic bodies are discussed.

Animals↗