SEARCH · PubMed Health

Results for “LIVER REGENERATION”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

PubMed2005

The delta opioid receptor 1 is expressed by proliferating bile ductules in rats with cholestasis: implications for the study of liver regeneration and malignant transformation of biliary epithelium.

In sharp contrast with the normal adult liver, the fetal human and rat livers and the liver of rats with cholestasis secondary to bile duct resection express the preproenkephalin mRNA, which codes for the endogenous opioid peptide Met-enkephalin. Furthermore, Met-enkephalin immunoreactivity is detected in hepatocytes and in proliferating bile ductules in the cholestatic rat liver. These data suggest that in cholestasis endogenous opioids may have a local effect in the cholestatic liver. As endogenous opioids exert their effect by binding to opioid receptors, the presence of opioid receptors in the cholestatic livers would support the hypothesis that Met-enkephalin plays a role in situ. Preliminary data presented in this manuscript reveals the expression of the delta opioid receptor in the liver of rats with cholestasis. This finding suggests that there is a scenario in which Met-enkephalin can bind to opioid receptors in the liver in cholestasis to exert a local effect. In vivo studies in this model of cholestasis with the use of opioid agonist and antagonist will shed light on the possible role of opioidergic regulation of liver regeneration. Studies on the effect of opiate antagonists on the evolution of cholestasis in this animal model may provide insight into the mechanisms of liver regeneration. In addition, as some conditions associated with cholestasis and bile ductular proliferation can be complicated by malignancy, the expression of the delta opioid receptor in malignant tumors of the biliary tree merits research.

Animals↗

PubMed1978

Fatty acid synthesis in the regenerating liver of the rat.

1. Synthesis de novo of fatty acids in the rat liver, measured per g wet wt. of tissue, was increased by a factor of about two, between 1 and 4 days after partial hepatectomy, compared with rates in sham-operated control rat livers. 2. There were no associated changes in the rates of liver cholesterol synthesis or of adipose-tissue fatty acid synthesis in rats after partial hepatectomy, compared with rates in sham-operated rats. 3. In regenerating livers, perfused under three different conditions, there was no alteration in the capacity for fatty acid synthesis compared with that of control rats. 4. The increased synthesis of fatty acids in regenerating liver was associated with insignificant increases in plasma concentrations of tricylglycerols and free fatty acids, with a decrease in content of liver glycogen, and with no change in hepatic activity of acetyl-CoA carboxylase. 5. The accelerated rate of synthesis of fatty adids in regenerating liver appears not to be due to any intrinsic alteration in hepatic capacity for fatty acid synthesis, but it may be caused by the continuous action on liver of unidentified circulating factors.

Acetyl-CoA Carboxylase↗

PubMed2005

Cobalt-protoporphyrin induced heme oxygenase overexpression and its impact on liver regeneration.

Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.

Alanine Transaminase↗

PubMed2004

Role of Hepatic Stellate Cells in the Early Phase of Liver Regeneration in Rat: Formation of Tight Adhesion to Parenchymal Cells.

We investigated activation mechanisms of hepatic stellate cells (HSCs) that are known to play pivotal roles in the regeneration process after 70% partial hepatectomy (PHx). Parenchymal liver cells (PLCs) and non-parenchymal cells (NPLCs) were isolated and purified from the regenerating livers at 1, 3, 7, 14 days after PHx. Each liver cell fraction was stained by immunocytochemistry using an anti-desmin antibody as a marker for HSCs, anti-alpha-smooth muscle actin (alpha-SMA) as a marker for activated HSCs, and 5-bromo-2'-deoxyuridine (BrdU) for detection of proliferating cells. Tissue sections from regenerating livers were also analyzed by immunohistochemistry and compared with the results obtained for isolated cell fractions. One and 3 days after PHx, PLC-enriched fraction contained HSCs adhered to PLCs. The HSCs adhered to PLCs were double positive for BrdU and alpha-SMA, and formed clusters suggesting that these HSCs were activated. However, HSC-enriched fraction contained HSCs not adhered PLCs showed positive staining for anti-desmin antibody but negative for anti-alpha-SMA antibody. These results suggest that HSCs are activated by adhering to PLCs during the early phase of hepatic regeneration.

Journal Article↗

PubMed1999

Comparative analysis of HPLC profile of cytosolic thymidine kinase activity between hepatoma and regenerating liver in rat with reference to phosphorylation.

Thymidine kinase (TK) activity in rat hepatoma JB1 and AH136B was mainly due to cytosolic TK and was much higher than that in rat regenerating liver. Two forms of cytosolic TK, designated as TK-I and TK-II, were revealed in addition to mitochondrial TK in anion-exchange high performance liquid chromatography (HPLC) of the enzyme extract from hepatoma JB1. During incubation of the enzyme extract at 20 degrees C in the presence of phosphatase inhibitor NaF, TK-II activity remained while TK-I activity almost disappeared. Thus, TK-II appeared to be more stable than TK-I. In Western blot analysis, TK-II was much more phosphorylated and exhibiting higher specific activity than TK-I. Meanwhile, regenerating liver derived from the rat 24 h after partial hepatectomy showed only TK-I activity, which completely disappeared after incubation at 20 degrees C even in the presence of NaF. Consequently, the presence of TK-II might account for the higher TK activity in hepatomas than in regenerating liver.

Animals↗

PubMed1998

FK506 promotes liver regeneration by suppressing natural killer cell activity.

We examined the mechanism of promotion of liver regeneration by tacrolimus hydrate (FK506), a potent immunosuppressant, after partial hepatectomy. The administration of FK506 significantly increased the bromodeoxyuridine (BrdU) labelling index at 36 and 48 h after 70% hepatectomy compared with the placebo group. Using the same model, we examined the effect of FK506 on the expression of hepatocyte growth factor (HGF) and transforming growth factor-beta 1 (TGF-beta 1) and found no changes in HGF and TGF-beta 1 mRNA expression in the liver or in the HGF protein concentration in plasma. We found that pretreatment with FK506 markedly reduced the activity and number of liver-resident natural killer (NK) cells at the time of partial hepatectomy. Our observations suggest that the promotion of liver regeneration by FK506 may be attributable to a reduction in the number of liver-resident NK cells and to inhibition of their activity.

Animals↗

PubMed1997

Expression of Bcl-2 family during liver regeneration and identification of Bcl-x as a delayed early response gene.

Induction of Bcl-2 and Bcl-x has been demonstrated in mitogen-stimulated lymphocytes in vitro, suggesting that these two apoptosis modulators may also play a role during proliferation. To explore this possibility in a physiological setting, mRNA expression of various Bcl-2 family members was examined during liver regeneration induced by partial hepatectomy, a well characterized in vivo model of cell cycle progression. After a 60% partial hepatectomy in C3H/HeN mice, the steady-state levels of Bcl-x mRNA exhibited a cyclical pattern, with peaks at 4 hours (early G1) and 48 to 72 hours (G1 phase of the second hepatocyte cell cycle). A1 and Bcl-2 mRNA were not detected, and the levels of two Mcl-1 mRNA species remained low without significant changes. The three pro-apoptotic members of the family, Bak, Bad, and Bax, all showed an early decline in mRNA levels when Bcl-x transcripts increased, followed by later peaks at 12, 24, and 48 to 72 hours, respectively. Experiments were subsequently conducted in C3H/HeJ mice, an endotoxin-resistant strain with slower liver regeneration marked by a protracted G1 phase. Even though immediate-early gene responses measured by c-myc induction remained intact, the timing of Bcl-x mRNA expression was delayed in C3H/HeJ mice. When C3H/HeN mice were pretreated with cycloheximide before hepatectomy, the early peak of Bcl-x mRNA at 4 hours was essentially abrogated whereas the immediate-early gene c-myc was hyperinduced, thus implicating Bcl-x as a delayed early response gene during liver regeneration. Bcl-x was localized in hepatocytes and by both immunohistochemistry and Western blot analysis, Bcl-xL protein reached highest levels at 12 hours (mid-G1), consistent with the expression of a delayed early gene. In summary, the expression profiles of Bcl-2 family members during liver regeneration suggest a cell-cycle-dependent regulation as well as a physiological role for these apoptosis-modulating genes during growth and proliferation.

Animals↗

PubMed1987

[Action of cytoplasmic factors from the regenerating liver on cholesterol esterification in the blood serum of rats with tetrachloromethane liver damage].

The effect of proliferation stimulating factors (PSF) obtained from regenerating liver on the cholesterol esterification in blood serum under deep tetrachloromethane intoxication has been studied in experiments with white rats. Three phases in dynamics of cholesterol content in blood serum have been picked out after a single tetrachloromethane injection. The content of total cholesterol and cholesterol esters reduces during the first phase (24 h), during the second phase (3-7th day) it increases and during the third phase (15th day) these values become normal. PSF injection does not produce any influence on the nature of blood cholesterol under deep tetrachloromethane intoxication, but stimulates the processes of cholesterol ester formation in blood serum.

Animals↗

PubMed1985

Effect of glucose, fructose, sorbitol and amino acid solutions employed in clinical medicine on the development of liver regeneration after partial hepatectomy.

The authors studied the effect of glucose (G), fructose (F), sorbitol (So), 4% Nutramin S Spofa (NuS) and Nutramin C Spofa (NuC) on development of liver regeneration. NuS is used clinically to improve a negative nitrogen balance, while the amino acid composition of NuC has a beneficial effect on the ornithine cycle and thus helps to normalize the NH3 level in patients with liver failure. Glucose seems to be the best substance for an optimal onset of liver regeneration. Its onset in rats given NuC was slower than in animals given NuS, but 48 h after partial hepatectomy there was no difference between NuC and NuS as regards the total DNA content and 96 h after the operation there was no difference as regards either the number of mitoses or the number of liver cells. In addition to reducing the plasma ammonia level, therefore, NuC also has a favourable effect on the development on liver regeneration.

Amino Acids↗

PubMed1980

Thymidine kinase: an inexpensive index of liver regeneration in a large animal model.

Most studies of liver regeneration have been restricted to small animals because of the cost of assessment of DNA synthesis by the standard method of thymidine incorporation in vivo. This paper presents the use of thymidine kinase as an inexpensive measure of regeneration in large animals. The use of the large model is advantageous because of the availability of serial blood and tissue samples from the same animal. Initially, the responses in thymidine kinase and thymidine incorporation over a period of 96 hr were shown to correspond well in rats subjected to 68% and 34% hepatectomy. Any delays could be attributed to different times of operation. A reproducible technique for 50% partial hepatectomy in the pig was developed, and the animals were studied by daily open liver biopsy for 7 days. The responses in thymidine kinase activity and mitotic indices showed tha peak regeneration occurred at 3-4 days. Levels of aspartate amino transferase were elevated sevenfold after partial hepatectomy but returned to normal within 96 hr. The levels of alkaline phosphatase and bilirubin were unaltered, confirming that the biliary drainage had not been compromised. This study offers the pig as another suitable model for the study of liver regeneration and thymidine kinase activity as a suitable index.

Animals↗

PubMedDate not supplied

Liver regeneration after extended right hemihepatectomy in patients with hilar or diffuse bile duct carcinoma.

BACKGROUND/AIMS: The degree to which liver size can be restored and the factors that determine liver regeneration after major hepatectomy are not well understood. METHODOLOGY: Liver volumes (LV) were estimated from computed tomography scans in 16 patients who survived with no evidence of cancer recurrence more than 1 year after extended right hemihepatectomy. RESULTS: The mean percentage of LV at 1 year was 75.7 +/- 9.5% and LV did not change significantly beyond 1 year after surgery. A significant correlation was observed between LV at 1 year and body surface area (r = 0.79, p < 0.001). A significant inverse correlation was observed between LV at 1 year and the plasma retention rate of indocyanine green at 15 min (the ICG 15 value) (r = -0.72, p < 0.01). CONCLUSIONS: In adults, the liver does not always regain its pre-operative size after hepatectomy. Patients' body size and intrinsic liver function or liver blood flow, represented by the ICG 15 value, may be related to regenerated liver size.

Aged↗

PubMed1989

[A comparative study of human placenta hydrolysate (Laennec) by intravenous or subcutaneous injection on liver regeneration after partial hepatectomy in normal and CCl4-induced cirrhosis rats].

The effect of human placenta hydrolysate (Laennec) on residual liver regeneration after about 70% partial hepatectomy (PH) in normal and CCl4-induced cirrhosis rats was examined. Both intravenous or subcutaneous injections of Laennec increased the regeneration rate of the residual liver after PH in normal rats. Intravenous injection of Laennec inhibited the decrease of liver total protein, and it decreased the level of serum transaminase (GOT, GPT). The regeneration rate of the residual liver after PH in CCl4-induced cirrhosis (CCl4-PH) rats increased by intravenous or subcutaneous injection of Laennec. Laennec also inhibited the increase of serum GOT caused by CCl4-PH. In the pathological examination of the regenerating liver, intravenous injection of Laennec minimized the pathological changes caused by PH or CCl4-PH such as vacuolation and necrosis in the hepatocytes. The enhancement of cytoplasma regeneration in hepatocytes was noticed by intravenous injection of Laennec, but that by subcutaneous Laennec was slight. Intravenous injection of Laennec also minimized the lipid deposition in liver caused by CCl4-PH. Laennec had no effect on the pseudolobule formation caused by CCl4. Thus, the effect of intravenous injection of Laennec on the liver regeneration in PH rats was much more potent than that by the subcutaneous injection.

Animals↗

PubMed2000

Fas engagement accelerates liver regeneration after partial hepatectomy.

Fas (CD95) is a receptor involved in induction of apoptotic cell death of Fas-bearing cells, including hepatocytes and T cells. Injection of Fas-specific antibodies into mice leads to fulminant hepatic failure and death. Fas also transduces growth-promoting signals in proliferating T cells, fibroblasts and some tumor cells. Here we show that partial hepatectomy, which triggers the immediate onset of liver regeneration, protected mice against the lethal effects of Fas-specific antibodies and prevented hepatocyte apoptosis in response to Fas engagement in vivo. Furthermore, Fas engagement accelerated liver regeneration after partial hepatectomy. Liver regeneration kinetics were delayed in mutant mice with decreased cell surface Fas expression (lpr mice). In contrast, regeneration was not delayed in lpr-cg mutant mice, which have a Fas mutation that prevents Fas-induced death but not Fas-dependent proliferative stimulation. Our results indicate that Fas engagement on cells in regenerating or healing tissues may promote cell growth.

Animals↗

PubMed2002

Expression of survivin during liver regeneration.

Survivin functions to suppress cell death and regulate cell division, and is observed uniquely in tumor cells and developmental cells. However, the expression and regulation of survivin in non-transformed cells are not well elucidated. Therefore, we investigated the expression of survivin in a murine liver regeneration model after partial hepatectomy and intraperitoneal carbon tetrachloride (CCl(4)) injection. We found that the expression of survivin transcript and protein were markedly elevated with the onset of DNA synthesis and remained elevated during G2 and M phases during liver regeneration. In a normal mouse liver cell line, over-expression of survivin resulted in a decrease in the G0/G1 phase and an increase in the S and G2/M phases, resulting in Rb phosphorylation. These findings suggest that survivin is dramatically expressed in a cell cycle-dependent manner during liver regeneration and provide a new insight into the regulation of cell proliferation and differentiation.

Animals↗

PubMed2001

[Augmenter of liver regeneration: a novel cytokine].

Augmenter of liver regeneration (ALR) is a novel cytokine which specifically stimulates hepatic cell proliferation and is able to rescue acute liver failure caused by carbon tetrachloride. This article reviews the discovery, tissue distribution, functions and prospect of ALR and its relationship with hepatic stimulatory substance (HSS).

Animals↗

PubMed1992

Regulation of adherens junction protein expression in growth-activated 3T3 cells and in regenerating liver.

The expression of the adherens junction proteins vinculin, alpha-actinin, and talin was compared in serum-stimulated 3T3 cells and in regenerating rat liver following partial hepatectomy. The levels of vinculin RNA and protein synthesis were rapidly and transiently elevated in growth-activated fibroblasts (peaking at 2-3 h) and in regenerating liver (at 4-8 h), preceding the replicative stage. alpha-Actinin expression was also induced, but more slowly (peaking at 6-8 h in 3T3 cells and at 28 h in regenerating liver), and remained elevated when DNA synthesis was proceeding in both systems. The expression of talin RNA was only slightly elevated in 3T3 cells following serum stimulation, and it remained largely unchanged in regenerating liver. The levels of RNA coding for fibronectin and for the beta 1-integrin subunit were transiently and extensively induced during liver regeneration (fibronectin with a peak at 8 h and beta 1-integrin at 12 h). The uvomorulin RNA level, and the expression of the liver-specific genes albumin and transthyretin, decreased in regenerating liver. The results suggest a physiologically significant regulation in the expression of structural components which link the extracellular matrix to the microfilament system in growth-activated fibroblasts and in regenerating liver.

3T3 Cells↗

PubMed1988

Liver regeneration.

Despite great advances in analysing hemodynamic, morphological and biochemical changes during the process of liver regeneration, the exact (patho)physiological mechanism is still unknown. A short survey of literature is given of the kinetics of liver regeneration and the significance of different hepatotrophic factors. A distinction is made between factors promoting cell hypertrophy and factors stimulating hyperplasia. Loss of cell-cell contact inhibition, metabolic overload or elimination of inhibitory substance are discussed as trigger mechanisms for cell proliferation after partial hepatectomy (PH). Trophic factors like insulin may create optimal conditions for cell growth. The Hepatic Stimulatory Substance (HSS) of LaBrecque is probably the most purified proliferation factor at present, but there are several claims for other hepatotrophic factors too.

Animals↗

PubMed1985

The endoplasmic reticulum in regenerating liver cells.

Light-microscopic analysis of mouse liver homogenates six days after partial hepatectomy, showed a higher percentage of nuclei with adherent cytoplasm than homogenates from normal liver. This observation was true for animals with either a slow or rapid recovery of body weight after the operation. The phenomenon was not a function of the changes in the proportions of parenchymal and non-parenchymal tissue in the regenerating liver. Electron-microscopic analysis of random samples from normal and regenerating livers indicated an increase in the perinuclear rough endoplasmic reticulum, and a displacement of the glycogen depots within the regenerating cells six days after partial hepatectomy. The marked resistance towards homogenization, shown by the cytoplasm of the regenerating cells, may have been due to the observed increase of perinuclear membranes. However, qualitative changes of the cell membranes and a general decrease of proteolytic activity connected with liver regeneration may also have contributed.

Animals↗