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PubMed1979

Influence of age and spironolactone on lysosomal enzyme activities, DNA and protein content of the rat liver after partial hepatectomy.

Measurements of DNA and protein content and determinations of lysosomal enzyme activities (beta-glucuronidase, beta-acetylglucosaminidase, cathepsin D) were performed in the rat liver following partial hepatectomy and spironolactone administration. The rats (SIV) were divided into three age-groups: 6 weeks old, 10 months old and 18 months old. 60 h after the administration of spironolactone (2 x 10 mg Aldactone/100 g body weight/day orally via gastric tube for 3 days) partial hepatectomy was performed. The removed two thirds of the liver and the regenerating liver (24 h after partial hepatectomy) were prepared for the biochemical examinations at 4 degrees C. The measurements of the enzyme activities were performed in liver homogenates. The results indicate that the administration of spironolactone cause (1) a weight increase in the normal as well as in the regenerating liver, especially in the older animals; (2) an increase of the protein content of the normal liver in the oldest age-group; (3) a decrease in the DNA content of the normal and regenerating liver of old rats, and (4) an age-dependent increase of decrease of the three lyososomal enzymes beta-glucuronidase, beta-acetylglucosamidase and cathepsin D.

Acetylglucosaminidase↗

PubMed1992

Role of diethylnitrosamine, 2-acetylaminofluorene and partial hepatectomy in the expression of glutathione-S-transferase-P and gamma-glutamyltranspeptidase in the early steps of rat liver carcinogenesis.

Three factors involved in the Solt and Farber model of rat liver carcinogenesis were studied alone and in various combinations: diethylnitrosamine (DEN) initiating dose, 2-acetylaminofluorene (2-AAF) feeding and partial hepatectomy. The administration of DEN alone (200 mg/kg) was able to switch on glutathione-S-transferase, placental type (GST-P) expression 3 weeks later at a low level (85 U/micrograms protein) which was stable for 10 weeks in the absence of histopathological lesions. During the same time, gamma-glutamyl transpeptidase (GGT) activity presented 2 waves of increase. The feeding of 0.03% 2-AAF for 2 weeks appeared as a determinant factor in the expression of GST-P protein as well as GGT induction (15- and 7-fold versus DEN alone, respectively). The addition of partial hepatectomy enhanced again GST-P expression (1.5-fold) and GGT induction (2-fold). However, GST-P foci increased in size, not in number while GGT foci increased both in size and in number. These data indicated that 2-AAF was a crucial component of the selection procedure since partial hepatectomy alone, with or without DEN initiation was inefficient in promoting GST-P expression. Therefore, 2-AAF would be able to promote the growth of GST-P-positive cells initiated by DEN, a mechanism likely responsible for its tumor-promoting effect.

2-Acetylaminofluorene↗

PubMed1981

Effects of hepatectomy, nephrectomy, and nephrectomy/uremia on the metabolism of parathyroid hormone in the rat.

Reports from several laboratories, showing extensive hepatic extraction of circulating parathyroid hormone, led us to examine the effect of near-total hepatectomy on the metabolism of the hormone to circulating fragments, and on its clearance from plasma. The rate of disappearance of (125)I-labeled and unlabeled bovine parathyroid hormone from plasma, and the appearance, disappearance, and chemical and immunochemical characteristics of circulating fragments were examined by gel filtration and either sequence-specific radioimmunoassays or sequence analysis using the Edman reaction. Results from awake rats subjected to near-total hepatectomy were compared with those found in sham-treated, nephrectomized, and short-term uremic rats (studied 2 d after nephrectomy). When compared with the sham-treated group, all other groups clear (125)I-labeled hormone more slowly; after hepatectomy, however, the clearance rate is most strikingly decreased. After injection of intact hormone, the concentration of carboxy-terminal fragments in the circulation of hepatectomized rats is greatly reduced at all time intervals when compared with that in sham-treated rats. Sequence analysis of plasma samples, collected from rats into which (125)I-labeled hormone had been injected, shows that carboxy-terminal fragments having positions 34 and 37 of the intact hormone sequence as their amino-terminal amino acids are abundant in sham-treated, nephrectomized, and nephrectomized/uremic rats, but are undetectable in hepatectomized rats. The data suggest that inasmuch as the liver in vivo generates most of the carboxy-terminal fragments resulting from the metabolism of injected hormone, specific cell types within the liver must be the principal locus of the responsible enzyme(s); thus, studies of the enzymic properties of isolated hepatic cells in vitro most likely will yield information of physiologic relevance to the metabolism of the hormone in the intact animal.

Animals↗

PubMed1993

Induction patterns of 70 genes during nine days after hepatectomy define the temporal course of liver regeneration.

Liver regeneration is an important process that allows for recovery from hepatic injuries caused by viruses, toxins, ischemia, surgery, and transplantation. Previously, we identified > 70 immediate-early genes induced in regenerating liver after hepatectomy, 41 of which were novel. While it is expected that the proteins encoded by these genes may have important roles in regulating progression through the G1 phase of the cell cycle during regeneration, we were surprised to note that many of these "early" genes are expressed for extended periods during the hepatic growth response. Here we define several patterns of expression of immediate-early, delayed-early, and liver-specific genes during the 9-d period after hepatectomy. One pattern of induction parallels the major growth period of the liver that ends at 60-72 h after hepatectomy. A second pattern has two peaks coincident with the first and second G1 phases of the two hepatic cell cycles. A third group, which includes liver-specific genes such as C/EBP alpha, shows maximal expression after the growth period. Although the peak in DNA synthesis in nonparenchymal cells occur 24 h later than in hepatocytes, most of the genes studied demonstrate similar induction in both cell types. This finding suggests that the G0/G1 transition occurs simultaneously in all cells in the liver, but that the G1 phase of nonparenchymal cells may be relatively prolonged. Finally, we examined the expression of > 70 genes in clinical settings that could induce liver regeneration, including after perfusion in a donor liver, hepatic ischemia, and fulminant hepatic failure. We found that a small number of early and liver-specific genes were selectively activated in human livers under these conditions, and we thereby provide a potential means of measuring the caliber of the regenerative response in clinical situations.

Adult↗

PubMed2003

Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy.

Stem cell factor (SCF) is a molecule with known proliferative effects on hematopoietic cells. More recent studies suggest that this molecule may also have effects on cellular differentiation and proliferation in other types of cells. The current investigations demonstrate that there is a large reservoir of SCF in the liver, that hepatic SCF levels change dramatically following partial hepatectomy in mice, and that SCF blockade, either by administration of anti-SCF antibodies or by using genetically altered, SCF-deficient mice, inhibits hepatocyte proliferation after partial hepatectomy; if SCF is replaced in the genetically SCF-deficient mice after partial hepatectomy, hepatocyte proliferation is restored to that seen in WT animals. Furthermore, SCF administration to IL-6 knockout mice also restores hepatocyte proliferation to normal. In vitro studies using primary mouse hepatocytes demonstrate that SCF causes hepatocyte proliferation and is induced by IL-6 and that treatment with anti-SCF antibodies inhibits IL-6-induced hepatocyte proliferation. Further in vivo studies in IL-6 knockout mice demonstrate that SCF administration to these animals increases p-stat3 levels, suggesting that the SCF-induced increase in hepatocyte proliferation in this system is stat3-mediated.

Animals↗

PubMedDate not supplied

Effect of nucleotide and nucleoside mixture on rats given total parenteral nutrition after 70% hepatectomy.

After partial hepatectomy rats were used as a model of patients with liver tumor after extensive hepatectomy. Supplementation of a nucleotide and nucleoside mixture to the total parenteral nutrition solution in rats after 70% hepatectomy resulted in earlier restoration of the nitrogen balance in the first 3 days than the solution without this supplementation. This supplementation had no unfavorable effects on the compositions of the blood and urine, and particularly the metabolites of nucleic acids such as uric acid, beta-alanine, and beta-aminoisobutyric acid. A suitable ratio of nucleotides plus nucleoside to amino acids was tentatively concluded to be 1:2 g N with a calorie supply of 400 kcal.

Animals↗

PubMedDate not supplied

Energy substrate for liver regeneration after partial hepatectomy in rats: effects of glucose vs fat.

This study evaluated the effects of glucose or fat on liver regeneration after partial hepatectomy in rats. Partial hepatectomy with resection of the median and left lateral lobes (67.31%) was performed on three rat groups. Two groups were infused with high-glucose (HG) or high-fat (HF) solutions intravenously 2 days before surgery. The control (C) group was allowed to eat instead of receiving intravenous infusions. Another group with sham operation only was also allowed to eat. Rats were killed 6, 24, 48, or 72 hours after the operation. Remnant liver weight, DNA synthetic rate, DNA content, and mitotic index were chosen as comparing indicators. Blood glucose, serum free fatty acid (FFA), total ketone bodies, and ketone body ratio were measured. Transmission electron microscopy was also used to observe the remnant liver. The results showed that the HG rat group had a better regenerative condition than did the HF rat group (p less than .01). Glucose is the predominant energy substrate when enough is offered during the immediate posthepatectomy phase. FFA utilization occurred only very early after partial hepatectomy, and it was remarkable in the control group, moderate in the HF group, and low in the HG group. Shifting of the energy substrate to FFA occurred only when glucose was not available for utilization. The disappearance and reappearance of glycogen, and accumulation of fat in cytoplasm as shown by transmission electron microscope pictures support this conclusion.

Animals↗

PubMed2005

Role of transforming growth factor-beta1 (TGF-beta1) in endotoxin-induced hepatic failure after extensive hepatectomy in rats.

Postoperative infections after hepatectomy sometimes lead to fatal hepatic failure, but the mechanism of the hepatic failure is unclear. Wistar rats underwent 90% hepatectomy, and were then divided into three groups: (i) the SAL group, injected with normal saline; (ii) the LPS group, injected with lipopolysaccharide (LPS) every day for 1 week; and (iii) the LPS plus TGF-Ab (LPS+TGF-Ab) group, injected with LPS with anti-transforming growth factor-beta1 (TGF-beta1) antibody. We investigated survival rates, TGF-beta1 expression in the liver, liver regeneration by proliferating cell nuclear antigen labeling index, hepatocyte apoptosis by single stranded DNA labeling index, and perisinusoidal fibrosis using Masson's trichrome staining. The LPS group (30.4%) had a significantly lower survival rate than the SAL group (84%) and tended to be lower than the LPS+TGF-Ab group (49.4%). Liver regeneration in the LPS group was significantly lower than in the other groups. In the LPS group, hepatocyte apoptosis and perisinusoidal fibrosis was significantly more remarkable, and TGF-beta1 expression was significantly higher than in the SAL group. TGF-beta1 enhanced by LPS plays an important role in the mechanism of hepatic failure by infections after hepatectomy, especially in inhibition of liver regeneration, and induction of hepatocyte apoptosis and perisinusoidal fibrosis.

Alanine Transaminase↗

PubMed2005

Evaluation of intraoperative autotransfusion filtration for hepatectomy and pancreatectomy.

BACKGROUND: Hepatectomy and pancreatectomy are often associated with significant intraoperative blood loss leading to postoperative anemia, which has been demonstrated to lead to increased perioperative morbidity, a prolonged hospital stay, and decreased overall survival. Cancer has remained an absolute contraindication to autotransfusion because of the unproven concern about reinfusion of malignant cells. Thus, the aim of this study was to test for the presence of malignant cells in autotransfused filtered blood in patients undergoing major pancreatic and liver resection. METHODS: A prospective study of 20 consecutive patients evaluated the presence of malignant cells from autotransfusion filtered blood after resection by flow cytometric and immunohistochemical methods. RESULTS: Ten patients underwent major hepatectomy for metastatic colorectal cancer, with a median blood loss of 500 mL (range, 200-700 mL). Three patients received a total of six units of packed red blood cells. Ten patients underwent pancreaticoduodenectomy for adenocarcinoma with a median blood loss of 400 mL (range, 200-1300 mL). Five patients received a total of nine units of packed red blood cells. Flow cytometry did not demonstrate the presence of any cytokeratin-positive carcinoma cells in filtered blood. CONCLUSIONS: Intraoperative autotransfusion for major hepatectomy in metastatic colorectal cancer and pancreatectomy for adenocarcinoma is safe and should begin to be evaluated in a phase II study for efficacy.

Adenocarcinoma↗

PubMed2006

Profile of plasma angiogenic factors before and after hepatectomy for colorectal cancer liver metastases.

BACKGROUND: Circulating angiogenic factors in patients with colorectal cancer liver metastases may promote tumor growth and contribute to liver regeneration after partial hepatectomy. METHODS: We analyzed blood samples from 26 patients with colorectal cancer liver metastases before and after liver resection and used samples from 20 healthy controls as a reference. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and hepatocyte growth factor (HGF) were measured, and levels were correlated with recurrence. RESULTS: The median preoperative levels of all four factors were significantly higher and more variable in colorectal cancer liver metastasis patients than in controls. HGF and bFGF levels increased significantly 3 days and 1 month after hepatectomy, respectively, and returned to near preoperative levels at 3 months. Postoperative VEGF and EGF levels remained relatively stably increased over 3 months. After a median follow-up of 19 months, 10 patients (42%) experienced recurrence. Higher preoperative VEGF and HGF levels correlated with subsequent recurrence (P = .018 and .021, respectively), and a preoperative adjusted total value of all four factors accurately identified patients at low, moderate, and high risk of recurrence (P = .034). Patients who experienced disease recurrence also had relatively higher bFGF levels 3 months after operation (P = .035). CONCLUSIONS: Plasma angiogenic factors are increased in patients with colorectal cancer liver metastases and remain increased at least 3 months after partial hepatectomy. Measurement of certain factors before and after hepatic resection can predict recurrence. Targeted biological agents may counteract the tumor-promoting effects of these circulating factors on subclinical disease.

Adult↗

PubMed1987

[Effects of TJN-101, a lignan compound isolated from Schisandra fruits, on liver fibrosis and on liver regeneration after partial hepatectomy in rats with chronic liver injury induced by CCl4].

TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. 1) Effect of TJN-101 on liver fibrosis was investigated in rats which were injected with CCl4 (1 ml/kg) subcutaneously twice a week for 12 weeks. TJN-101 was given orally at the dose of 10 or 30 mg/kg/day for 6 or 3 weeks beginning on the 6th or 9th week after the start of CCl4-intoxication, respectively. The elevations of serum transaminase activities and the increase of liver 4-hydroxyproline content were observed depending on the period of CCl4-intoxication. These changes were marked on the 9th and 12th weeks after. In the histopathological study, the degenerative fatty change on the 6th week after and the formation of pseudolobule caused by fibrosis proliferation on the 9th or 12th week after were mainly observed. When rats were treated with TJN-101, the abnormalities in biochemical parameters and the fibrosis proliferation caused by CCl4-intoxication were improved. 2) Chronic liver injury was induced by the treatment with CCl4 (1 ml/kg) subcutaneously twice a week for 10 weeks to investigate the effect of TJN-101 on liver regeneration after partial hepatectomy. TJN-101, which was given orally at the dose of 10, 30 or 100 mg/kg/day for 6 days from the 1st day after partial hepatectomy, dose-dependently increased the liver regeneration rate and improved the serum BSP retention rate. These results suggest that TJN-101 suppresses the fibrosis proliferation and accelerates both the liver regeneration and the recovery of liver function after partial hepatectomy in chronic liver injury.

Administration, Oral↗

PubMed1994

[Modification of surface phenotype and function in intrahepatic lymphocytes during liver regeneration after partial hepatectomy].

In the intrahepatic lymphocyte fraction (IHL) of mice whose livers have been perfused by Ca+2 and Mg+2 free Hank's balance salt solution, flow cytometric analysis reveals various cells similar to those found in the spleen (CD3+ cell, CD4+ cell, CD8+ cell, alpha beta TCR+ cell, gamma delta TCR+ cell, Thy1.2+ cell, B220+ cell and asialo-Gm1+ cell). The cytotoxic activity against YAC-1 cells in IHL is significantly higher than that in spleen cells. Furthermore, IHL has cytolytic activity against syngeneic thymoma BW5147 cells which is not found in spleen cells. Both cytotoxic activities of IHL are greatly weakened by the pretreatment of IHL with anti asialo-Gm1 Ab and rabbit complement. During liver regeneration after a partial hepatectomy, the percentages of lymphocyte subsets of IHL such as alpha beta TCR+ cells, gamma delta TCR+ cells and asialo-Gm1+ cells transiently increase 2 days after the partial hepatectomy and their cytotoxic activities against YAC-1 and BW5147 cells also reach a peak at that time. It is well known that the peak of mitotic index in regenerating parenchymal liver cells peaks 2 days after a partial hepatectomy and that the number of Pit cells peaks 10 to 14 days after. Compared with the time for reaching the highest mitotic index in regenerating parenchymal liver cells, the proliferation of Pit cells comes very late. It has not been clear which proliferation process in parenchymal liver cells is suppressed by activated Pit cells. Our findings in this paper reveal that the percentages and the cytotoxic activities of asialo-Gm1+ cells in IHL reach their peak 2 days after an operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1979

The release and metabolism of pancreatic hormones after major hepatectomy in the dog.

Major hepatectomy in the dog induced a 50% decrease in peripheral serum glucose, a 11-fold increase in portal plasma glucagon and a 36-fold increase in the portal glucagon/insulin ratio 3 hr after operation. Peripheral serum glucose levels were inversely correlated to the logarithmic value of portal plasma glucagon (r = -0.50, p less than 0.01) and that of the portal glucagon/insulin ratio (r = -0.85, p less than 0.01) for 1-6 hr after operation. The ratio of peripheral to portal plasma glucagon was also inversely correlated to the logarithmic value of portal plasma glucagon (r = -0.59, p less than 0.01). In case of glucose infusion, plasma glucagon levels were not elevated after major hepatectomy. The data suggest that glucose deficiency after major hepatectomy in the dog may cause hyperglucagonemia with an enhanced glucagon requirement.

Animals↗

PubMed1978

Increase of the gluconeogenic and decrease of the glycolytic capacity of rat liver with a change of the metabolic zonation after partial hepatectomy.

During the first 72 h after 67% partial hepatectomy of female Wistar rats (160 g) the specific activities [mumol X min-1 X (g liver)-1] of the glucogenic glucose-6-phosphatase and fructose-bisphosphatase and of the glycolytic hexokinase and 6-phosphofructokinase remained essentially constant. However, the activity of the glycolytic pyruvate kinase (L- plus M2-type) was decreased slightly and that of glucokinase was decreased markedly to below 30%, while the glucogenic phosphoenolpyruvate carboxykinase was increased to over 200%. Between 10 and 40 h after partial hepatectomy, when the proliferation started in the periportal area, a shift of the glucogenic glucose-6-phosphatase-rich zone from its normal periportal to an intermediate or even perivenous position was observed histochemically. After 48 h, when the proliferation was no longer restricted to the periportal zone, the normal glucose-6-phosphatase zonation (as before partial hepatectomy) was restored. Glycogen was degraded rapidly during the first 4 h after operation; it was later repeatedly resynthesized and degraded in correlation with the feeding rhythm of the animals. The zonation of glycogen metabolism was in accord with the observed zonation of glucose-6-phosphatase.

Animals↗

PubMedDate not supplied

Hepatic regeneration after partial hepatectomy in mice infected with Schistosoma mansoni, at the acute and chronic phases of the disease.

Outbred male albino mice normal or infected with 30 cercariae of Schistosoma mansoni (LE strain) were submitted to 65% hepatectomy during the acute (70 days) and chronic phase (160 days) phases of the disease. A group of the infected animals was treated with 400 mg/kg of oxamniquine during the acute phase before hepatectomy. Non-infected, infected and treated but not hepatectomized animals were kept as controls. Hepatic regeneration was evaluated by incorporation of tritiated thymidine, intraperitoneally injected into non-hepatectomized and hepatectomized animals, 24 hours after surgery. The results showed that removal of 65% of the hepatic parenchyma, during the acute phase, led to a statistically significant increase of thymidine incorporation, when compared with the uninfected hepatectomized controls. This phenomenon was not observed at the chronic phase. Treatment with oxamniquine administered during the acute phase led to a decrease in thymidine incorporation rate 160 days after infection (90 days after treatment) and 24 hours after hepatectomy. The data suggest that infection with S. mansoni represents a considerable stimulus for the regenerative capacity of the liver during the acute, but not the chronic phase of disease.

Acute Disease↗

PubMed2006

The effect of laser on remanescent liver tissue after 90% hepatectomy in rats.

PURPOSE: To evaluate the effect of laser beam on reminiscent liver after partial hepatectomy 90%. METHODS: Wistar rats, (N=42), were divided into six groups with seven specimens each. The partial hepatectomy (HP) was performed in all animals through exeresis of approximately 90% of the liver parenchyma. The animals from groups HP and Laser application, HPL24, HPL48 and HPL72 undertook laser irradiation carried out through application (dose of 22.5 J/cm2) in five different sites in the reminiscent liver. The rats were then sacrificed 24, 48 and 72 hours after HP procedure, for the liver regeneration analysis,using the Proliferating Cell Nuclear Antigen (PCNA),and for dosage of serum aminotransferases. RESULTS: Were demonstrated an increase of the serum levels of alanine aminotransferase for the group of 24 hours and a decrease for the group of 72 hours exposed to laser. The index of marked cells had a considerable more improvement for the group of 72 hours exposed in laser compared to other groups. CONCLUSION: Laser did not cause hepatic injuries additional to the partial hepatectomy and perhaps led to a benefit by stimulating the proliferative activity.

Animals↗

PubMed1980

99mTc-PI as safe and easy scintigraphy after hepatectomy.

Hepatobiliary scintigraphy with 99mTc-PI was performed on 16 patients after various types of hepatectomy for either primary or secondary liver tumor. 99mTc-PI scintigraphy was found very useful, especially in regard to clinical evaluation of indistinct low-uptake areas observed on a 99mTc colloid liver scintigram in the regenerating liver after hepatectomy. Both tests were conducted successively within a couple of weeks. Colloid scintigrams after hepatectomy were divided into two groups according to the sites of indistinct low-uptake areas; one showed them near the resected margin of the regenerating liver (Type I), and the other showed them in both marginal and intrahepatic. regions (Type II). Of these 16 patients, 8 showed Type I and 7 showed Type II. The remaining one was excluded for postsurgical complications. By comparing the colloid scintigram with the 99mTc-PI scintigram, in all the cases of Type I indistinct low-uptake areas were found to be the hilum with a shifted common bile duct. On the other hand, in 2 cases of Type II indistinct low-uptake areas were caused by the hilum accompanied by the dilated bile ducts. In the remaining 5, indistinct low-uptake areas were not identified as bile ducts but were confirmed to be a recurrence of the tumor.

Adult↗

PubMed1988

Significance of activation of reticuloendothelial function after hepatectomy in cirrhotic rats.

Effect of hepatectomy on the prognosis of cirrhotic rats prepared by oral administration of thioacetamide was studied from the standpoint of the reticuloendothelial function and energy metabolism of the liver. OK-432, a streptococcal preparation, was used to activate reticuloendothelial functions. Administration of OK-432 to cirrhotic rats prior to 70% hepatectomy significantly prevented the elevation of serum GOT, GPT and LDH, the prolongation of blood coagulation and the decrease of serum complement level. Hepatic ATP synthesis and RNA content were significantly increase by the use of OK-432. These findings suggest that activation of reticuloendothelial functions at the time of massive hepatectomy in cirrhotic rats may diminish hepatic injury, maintain serum complement level, and improve protein synthesis of the liver.

Animals↗