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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↗

Treatment of centrally located hepatocellular carcinoma with central hepatectomy.

BACKGROUND: For treatment of centrally located hepatocellular carcinoma (HCC), central hepatectomy (including central trisegmentectomy [Couinaud's segments 4, 5, and 8] and anterior segmentectomy [Couinaud's segments 5 and 8]) may have an important advantage (ie, preservation of nontumorous parenchyma) over conventional lobectomy or extended lobectomy. For determination of the efficacy of this technique, we compared the outcomes of patients with HCC who underwent treatment with the central and conventional methods. PATIENTS AND METHODS: In our institute, 52 patients with HCC underwent treatment with central hepatectomy (group 1) and 63 patients with comparable tumor size underwent treatment with conventional major hepatectomy (group 2) from November 1993 to April 1999. Overall patient survival and disease-free survival rates were calculated and analyzed. The possible prognostic risk factors for patient and disease-free survival in group 1 were analyzed. RESULTS: Group 1 had comparable overall patient and disease-free survival rates with those of group 2. Vascular invasion, higher pathology grading, and resection margin less than 1 cm appeared to be the prognostic factors for overall patient survival, and vascular invasion was the only risk factor for disease-free survival. CONCLUSION: Central hepatectomy is a safe and effective operative procedure for the treatment of centrally located HCC. The patient and disease-free survival rates were the same as those of conventional major hepatectomy. Although it is technically more demanding, central hepatectomy preserves more nontumor liver parenchyma, which is important for the survival of those patients with liver cirrhosis.

Adult↗

Paradoxical effects of glucose feeding on liver regeneration and survival after partial hepatectomy.

Although glucose is regularly administered to patients after partial hepatic resection, its contribution to survival and/or liver regeneration is unclear. To examine this question fed and anesthetized rats underwent 68% or 90% hepatectomy and received either oral 20% glucose solution or tap water (controls) ad lib for 24 h. Survival was compared by life table analysis and the regeneration response measured by 3H-thymidine uptake into liver deoxyribonucleic acid (DNA). Profound hypoglycemia (60 +/- 8 mg/dl) following 90% hepatectomy in controls was corrected by glucose feeding (99 +/- 25 mg/dl) and survival was enhanced (75 +/- 0.09% vs. 42 +/- 0.1%, p less than 0.01). No deaths occurred in the 68% hepatectomy groups wherein untreated hypoglycemia was not as severe (106 +/- 6 mg/dl). However, after 68% hepatectomy glucose adversely affected the regeneration response. We conclude that glucose feeding corrected the life threatening hypoglycemia following 90% hepatectomy. Prophylactic glucose administration after 68% hepatectomy reduced the liver regeneration response. Selective glucose administration to prevent lethal hypoglycemia may provide optimal survival and conditions for regeneration.

Administration, Oral↗

Pretreatment with IFN-gamma decreases infectious complications after partial hepatectomy in the rat.

Infectious postoperative complications occur commonly after hepatectomy and may lead to a long hospital stay or death. The potential beneficial effects of interferon-gamma (IFN-gamma) in this setting were evaluated in a model of hepatectomy and sepsis in rodents. Incidence of bacterial translocation was measured in animals on days 1, 2, and 5 after partial hepatectomy. Macrophage function was quantified by in vitro tumoricidal activity and superoxide anion (O2-) production. Survival after partial hepatectomy and cecal ligation and puncture (CLP) was recorded. After partial hepatectomy, bacterial translocation was decreased on days 1 and 2 in animals pretreated with IFN-gamma (p < 0.05). Macrophages from animals treated with IFN-gamma had higher in vitro tumoricidal activity and production of O2- (p < 0.05). Hepatectomized animals pretreated with IFN-gamma had an increased survival after CLP (p < 0.05). IFN-gamma may be useful in decreasing the incidence of infectious complications after partial hepatectomy.

Animals↗

Early effects of total hepatectomy on haemodynamic state and organ uptake of catecholamines in the pig.

In a previous study, we showed that plasma concentrations of catecholamines were increased during the anhepatic phase in pigs. In this study, we investigated if a constant depth of anaesthesia would prevent these changes and, if not, if the changes were caused by impaired extraction of catecholamines. We measured arterial and venous pressures, heart rate and cardiac output in 10 anaesthetized pigs. Hepatic arterial and portal venous flows were measured. Blood for measurement of catecholamines was sampled from carotid and pulmonary arteries and portal, hepatic and renal veins. After a 2-h observation period, the liver was removed and the circulation reconstituted. Measurements were made and samples obtained for another 2 h. Catecholamine concentrations increased 2-10-fold after hepatectomy. Before hepatectomy, noradrenaline was extracted by the lung (mean extraction ratio 23 (SEM 8)%) and the liver (30 (11)%); after hepatectomy, there was extraction by the kidney (24 (12)%) but extraction by the lung (29 (8)%) was unchanged. Before hepatectomy, adrenaline was extracted predominantly by the kidney (73 (5)%) and the liver (70 (6)%), with minimal extraction by the lung; after hepatectomy, extraction by the lung increased (25 (4)%) and decreased slightly in the kidney (56 (6)%). While mean arterial pressure did not change, heart rate increased by approximately 50% and cardiac index declined (ns) within 2 h after hepatectomy. There was a sharp increase in pulmonary vascular resistance after removal of the liver and changes correlated with increases in arterial plasma concentrations of catecholamines.

Anesthesia, General↗

Rescue hepatectomy for initial graft non-function after liver transplantation.

BACKGROUND: Early retransplantation is the therapy of choice in patients with initial graft nonfunction (INF). In rare cases the patients' conditions deteriorate dramatically with severe cardiovascular and/or pulmonary insufficiency while on the waiting list for retransplantation. In this life-threatening situation removal of the graft and temporary portocaval shunt before allocation of a new liver proved to be effective. Our experience with this two-stage hepatectomy and subsequent liver transplantation in patients with complicated INF is reported. METHODS: Hepatectomy was performed in 20 patients with INF associated with severe cardiovascular and pulmonary insufficiency while on the waiting list for emergency liver retransplantation. The mean age was 41.75+/-16.64 years. The time period between primary transplantation and hepatectomy was 2.80+/-2.84 days with a range from 1 to 9 days. RESULTS: Hepatectomy reduced the need for vasopressive agents and improved pulmonary function in the majority of patients. Four patients died before a liver was available due to brain death in one patient and multiorgan failure in three patients. In the remaining 16 patients liver transplantation could be performed after 19.82+/-15.34 hr (range 6.58 to 72.50 hr). Two of the 16 transplanted patients died on the first postoperative day due to multiorgan failure and pneumonia. The remaining 14 of 16 patients survived retransplantation, but 7 died between days 13 and 105 mostly due to sepsis. Seven patients were discharged from the hospital in good condition and show long-term survival. CONCLUSION: Hepatectomy was able to stabilize the cardiovascular and pulmonary function. This study confirms the beneficial effects of hepatectomy and subsequent liver transplantation as a life-saving procedure in patients with INF complicated by cardiovascular and/or pulmonary instability.

Adolescent↗

Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to evaluate prognostic factors in patients with recurrence after curative resection of hepatocellular carcinoma (HCC) and to identify selection criteria for repeat resection. SUMMARY BACKGROUND DATA: Recent studies have demonstrated that repeat hepatectomy is effective for treating intrahepatic recurrent HCC in selected patients. However, the prognostic factors in these patients have not been fully evaluated. METHODS: From October 1994 to December 2000, 334 patients underwent primary resection for HCC, and 67 received a 2nd hepatectomy for recurrent HCC. The survival results in these 67 patients were analyzed, and prognostic factors were determined using 38 clinicopathological variables. The prognosis and operative risk in 11 and 6 patients who received a 3rd and 4th resection were also evaluated. RESULTS: The overall 1-, 3-, and 5-year survival rates of the 334 patients after primary hepatectomy were 94%, 75%, and 56%, while those of the 67 patients after a 2nd resection were 93%, 70%, and 56%, respectively. There was no difference in survival (P = 0.64). All of the patients who underwent a 3rd or 4th are currently alive at a median follow-up of 2.5 and 1.4 years, respectively. The operative time and blood loss in the 2nd resection in patients who underwent a major primary resection were not different from those in patients who underwent minor hepatectomy at the 1st resection, and there were also no differences in these variables among the 2nd, 3rd, and 4th resections. In a multivariate analysis, absence of portal invasion at the 2nd resection (P = 0.01), single HCC at primary hepatectomy (P = 0.01), and a disease-free interval of 1 year or more after primary hepatectomy (P = 0.02) were independent prognostic factors after the 2nd resection. Twenty-nine patients with all 3 of these factors showed 3- and 5-year survival rates of 100% and 86%, respectively, after the 2nd resection. CONCLUSIONS: Repeat hepatic resection is the treatment of choice for patients who have previously undergone resection of a single HCC at the primary resection and in whom recurrence developed after a disease-free interval of 1 year or more and the recurrent tumor had no portal invasion.

Adult↗

Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database.

OBJECTIVE: To assess the trends in perioperative outcome of hepatectomy for hepatobiliary diseases. METHODS: Data of 1222 consecutive patients who underwent hepatectomy for hepatobiliary diseases from July 1989 to June 2003 in a tertiary institution were collected prospectively. Perioperative outcome of patients in the first (group I) and second (group II) halves of this period was compared. Factors associated with morbidity and mortality were analyzed. RESULTS: Diagnoses included hepatocellular carcinoma (n = 734), other liver cancers (n = 257), extrahepatic biliary malignancies (n = 43), hepatolithiasis (n = 101), benign liver tumors (n = 61), and other diseases (n = 26). The majority of patients (61.8%) underwent major hepatectomy of > or = 3 segments. The overall hospital mortality and morbidity were 4.9% and 32.4%, respectively. The number of hepatectomies increased from 402 in group I to 820 in group II, partly as a result of more liberal patient selection. Group II had more elderly patients (P = 0.006), more patients with comorbid illnesses (P = 0.001), and significantly worse liver function. Nonetheless, group II had lower blood loss (median 750 versus 1450 mL, P < 0.001), perioperative transfusion (17.3% versus 67.7%, P < 0.001), morbidity (30.0% versus 37.3%, P = 0.012), and hospital mortality (3.7% versus 7.5%, P = 0.004). On multivariate analysis, hypoalbuminemia, thrombocytopenia, elevated serum creatinine, major hepatic resection, and transfusion were the significant predictors of hospital mortality, whereas concomitant extrahepatic procedure, thrombocytopenia, and transfusion were the predictors of morbidity. CONCLUSIONS: Perioperative outcome has improved despite extending the indication of hepatectomy to more high-risk patients. The role of hepatectomy in the management of hepatobiliary diseases can be expanded. Reduced perioperative transfusion is the main contributory factor for improved outcome.

Adult↗

Perioperative parenteral tranexamic acid in liver tumor resection: a prospective randomized trial toward a "blood transfusion"-free hepatectomy.

OBJECTIVE: To examine the feasibility of a real "blood transfusion"-free hepatectomy in a large group of patients with liver tumors. SUMMARY BACKGROUND DATA: Bleeding control and blood transfusion remains problematic in liver resection. A real "blood transfusion"-free hepatectomy in a large group of patients has rarely been reported. The impact of tranexamic acid (TA), an antifibrinolytic agent, on blood transfusion in liver resection is unknown. METHODS: A prospective double-blind randomized trial was performed on elective liver tumor resections. In group A, TA 500 mg was intravenously administered just before operation followed by 250 mg, every 6 hours, for 3 days. In group B, only placebo was given. The patients' background, blood transfusion rates, and early postoperative results in the 2 groups were compared. Factors that influenced blood requirement were analyzed. RESULTS: There were 108 hepatectomies in group A and 106 hepatectomies in group B. The patients' backgrounds, operative procedures, and hepatectomy extent did not significantly differ between the 2 groups. Although the differences of the operative morbidity and postoperative stay were not significant, a significantly lower amount of operative blood loss, lower blood transfusion rate, shorter operative time, and lower hospital costs were found in group A patients. No patient in group A received blood transfusion. No hospital mortality occurred in either group. Tumor size and use of TA were independent factors that influenced blood transfusion. CONCLUSIONS: Perioperative parenteral use of TA reduced the amount of operative blood loss and the need for blood transfusion in elective liver tumor resection. A real "blood transfusion"-free hepatectomy may be feasible with the assistance of parenteral TA.

Aged↗

Relationship between glutathione and polyamine metabolism after partial hepatectomy in alcohol-treated rats.

In a liver regeneration inhibiting model after partial hepatectomy in rats, we determined hepatic glutathione concentration and studied its relation with polyamine, an indicator of liver regeneration. Experiment 1: Male ODS rats and Wistar rats as control were maintained with vitamin C-deficient diets for 2 weeks. In the alcohol group, 3 g/kg of ethanol was administered orally 1 hr before partial hepatectomy. Experiment 2: Wistar rats were divided into four groups, according to the presence or absence of alcohol and vitamin E (VE), and a 6-week pair-feeding was done. As for partial hepatectomy, about 70% of the total liver was excised. As a result, in experiment 1, hepatic glutathione levels were significantly decreased by acute alcohol administration in both ODS and Wistar rats, and its level of alcohol administration group of ODS rats was the lowest. Hepatic ornithine decarboxylase activity and putrescine level 4 hr after partial hepatectomy showed almost a similar behavior, being the lowest in the alcohol administration group of ODS rats. In experiment 2, hepatic glutathione level showed no influence by chronic alcohol administration, but was the lowest in the VE-deficient alcohol administration group. Hepatic ODC activity and putrescine level 4 hr after partial hepatectomy showed no influence by chronic alcohol administration, but was the lowest in the VE-deficient alcohol administration group. These results clarified that intrahepatic glutathione levels before partial hepatectomy were decreased in the models in which hepatic ODC activities after surgery were suppressed.

Animals↗

Hepatic regeneration and metabolism after partial hepatectomy in diabetic rats: effects of insulin therapy.

The effect of insulin deficiency on liver regeneration has been assessed in untreated v. insulin-treated streptozotocin (65 mg kg-1) diabetic rats, 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased from 12 to 48 h after partial hepatectomy and insulin treatment caused a further minor increase at 24 h. [6-3H]Thymidine uptake in untreated rats peaked at 24 h (12.5 +/- 3.4% of total cells labelled). Insulin therapy produced a delayed 168% rise in uptake at 48 h. Insulin deficiency alone in sham-operated animals caused a 33% decrease in hepatic [ATP], while [ADP] rose by 43% and [AMP] by 86% at 12 h. Partial hepatectomy produced only minor further abnormalities in untreated animals. Insulin therapy increased hepatic [ATP] and decreased [ADP] and [AMP] 12 h after partial hepatectomy, but [ATP] remained decreased (15%) and [ADP] and [AMP] increased (45% and 73% respectively) compared with insulin-treated sham-operated controls. Metabolite changes observed after partial hepatectomy in untreated animals, including a decrease in hepatic [glycogen] and increases in [triglyceride] and the ratios of [lactate]:[pyruvate] and [3-hydroxybutyrate]:[acetoacetate], were partially reversed by insulin treatment. Insulin deficiency thus impairs regeneration after partial hepatectomy and magnifies the decline in hepatic intracellular energy state and the metabolite changes associated with liver regrowth.

Adenine Nucleotides↗

Effectiveness of chemical biliary duct embolization for chemical hepatectomy.

BACKGROUND AND AIMS: The high recurrence of hepatolithiasis and high operative trauma of hepatectomy necessitate new therapeutic approaches. Thus, this study was designed to (i) investigate the effectiveness of chemical biliary duct embolization (CBDE) for chemical hepatectomy; and (ii) to determine the mechanism of CBDE. METHODS: The median biliary ducts in rats were injected with phenol or absolute ethanol alone, or in conjunction with cyanoacrylate. The effectiveness of CBDE for chemical hepatectomy was assessed by investigating histology, in situ hybridization for Fas and transforming growth factor (TGF)-beta1, immunohistochemistry for alpha-smooth muscle actin, and reverse transcription-polymerase chain reaction (RT-PCR) for procollagen I mRNA. RESULTS: Histologically, phenol or absolute ethanol plus cyanoacrylate could embolize the targeted bile duct and promote hepatic fibrosis and atrophy in the embolized lobe better than using phenol or ethanol alone. In addition, CBDE accelerated hepatocellular apoptosis via up-regulation of Fas, thereby resulting in the death of hepatocytes, which were replaced by proliferative bile ductules and collagen. Importantly, the hepatocytes disappeared completely in the periphery of the embolized lobe, thus achieving the desired effects of chemical hepatectomy. Further investigation indicated that CBDE initiated progressive fibrogenic processes of chemical hepatectomy via up-regulation of TGF-beta1, which greatly enhanced the synthesis of collagen. Indeed, higher levels of TGF-beta1 and procollagen I mRNA were observed in the phenol embolization group than in any other group. CONCLUSION: Chemical biliary duct embolization, especially using phenol plus cyanoacrylate, might achieve the effects of chemical hepatectomy.

Animals↗

Involvement of retinoic acid-induced transglutaminase activity in zonal differences of hepatocyte proliferation after partial hepatectomy.

BACKGROUND: The authors have recently demonstrated that there is inverse correlation between transglutaminase (TGase) activity and DNA synthesis in periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) at 1 day after partial hepatectomy in rats. In order to ensure the involvement of TGase in the differential growth capacities between periportal and perivenous regions of regenerating liver, the aim of this study was to investigate the effect of retinoic acid, an inducer of TGase expression, on zonal differences of hepatocyte proliferation between PPH and PVH isolated from regenerating rat liver. METHODS: Regenerating liver was prepared by 70% partial hepatectomy. PPH and PVH subpopulations were isolated by the digitonin/collagenase perfusion technique. Cell cycle was evaluated for incorporation of BrdU into hepatocytes and detected by flow cytometric analysis. TGase activity was determined by incorporation of 14C-putrescine into dimethylcasein. RESULTS: When retinoic acid was injected immediately after partial hepatectomy, TGase activity greatly increased in both PPH and PVH at 1 day after partial hepatectomy, and activity was higher in PPH than in PVH. DNA synthesis in both subpopulations did not increase 1 day after partial hepatectomy, with peaks of DNA synthesis shifting to 2 days, and synthesis was higher in PVH than in PPH. CONCLUSION: These results suggest that TGase might be involved in differential growth capacities between periportal and perivenous regions of regenerating rat liver after partial hepatectomy.

Animals↗

Serum lipid and lipoprotein alterations represent recovery of liver function after hepatectomy.

BACKGROUND: The assessment of liver function during human liver regeneration is necessary to prevent unexpected liver failure and to prepare for further treatment. We selected patients prospectively and measured serum lipid and lipoprotein levels to identify which lipids and lipoproteins could represent recovery of liver function in human liver regeneration. METHODS: Thirty selected patients who underwent hepatectomy were divided into three groups depending on the serum hyaluronate (HA) level and the type of liver resection. RESULTS: We found three patterns of lipid and lipoprotein alterations after hepatectomy. Among the lipids and lipoproteins examined, the serum beta-lipoprotein and low-density lipoprotein (LDL) levels were significantly different among the groups at 7 days after hepatectomy. The alteration of the apolipoprotein (Apo) B level was similar to that of LDL. The LDL level was correlated with both beta-lipoprotein and Apo B before hepatectomy (r=0.653 and 0.894, respectively) and at 7 days after hepatectomy (r=0.841 and 0.943, respectively). CONCLUSION: Serum HA before hepatectomy can reflect postoperative liver function depending on the type of liver resection. Recovery of the beta-lipoprotein and LDL levels can reflect the recovery of liver function in human liver regeneration within the early period in association with the Apo B level.

Aged↗

Hepatic infection by thymidine kinase-positive and thymidine kinase-negative herpes simplex virus after partial hepatectomy.

Herpes simplex virus (HSV) infection of mouse liver after partial hepatectomy was studied. Partial hepatectomy resulted in the rapid onset of cellular DNA synthesis and the appearance of many mitotic figures (peak, 3 days after surgery). Similar changes were not seen in control animals. After partial hepatectomy, the mice were infected with thymidine kinase-positive (TK+) and -negative (TK-) HSV to investigate virus titers in liver tissue during liver cell replication. In control unoperated mice, liver titers of TK+ HSV (2 X 10(3) PFU/g) were greater than those of mice inoculated with TK HSV (4 X 10(1) to 5 X 10(2) PFU/g). After partial hepatectomy, TK+ and TK- HSV titers increased, and peak TK+ and TK- HSV titers were similar (6 X 10(5) to 8 X 10(5) PFU/g). Hepatic infection was further investigated by infectious center (IC) assays. The numbers of ICs for TK+ HSV increased 50-fold after partial hepatectomy, whereas the increase was less for TK- HSV. From the results of these studies, we hypothesize that the increase in hepatic TK+ HSV after hepatectomy may have been largely due to the increase in ICs, whereas the increase in hepatic TK- HSV was due, in part, to the increase in ICs, but may also have been due to the enhanced synthesis of TK- HSV in replicating liver cells.

Animals↗

Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events.

In understanding mechanisms of liver repopulation with transplanted hepatocytes, we studied the consequences of hepatic polyploidization in the two-thirds partial hepatectomy model of liver regeneration. Liver repopulation studies using genetically marked rodent hepatocytes showed that the number of previously transplanted hepatocytes did not increase in the liver with subsequential partial hepatectomy. In contrast, recipients undergoing partial hepatectomy before cells were transplanted showed proliferation in transplanted hepatocytes, with kinetics of DNA synthesis differing in transplanted and host hepatocytes. Also, partial hepatectomy caused multiple changes in the rat liver, including accumulation of polyploid hepatocytes along with prolonged depletion of diploid hepatocytes, as well as increased senescence-associated beta-galactosidase and p21 expression. Remnant hepatocytes in the partially hepatectomized liver showed increased autofluorescence and cytoplasmic complexity on flow cytometry, which are associated with lipofuscin accumulation during cell aging, and underwent apoptosis more frequently. Moreover, hepatocytes from the partially hepatectomized liver showed attenuated proliferative capacity in cell culture. These findings were compatible with decreased proliferative potential of hepatocytes experiencing partial hepatectomy compared with hepatocytes from the unperturbed liver. Attenuation of proliferative capacity and other changes in hepatocytes experiencing partial hepatectomy offer novel perspectives concerning liver regeneration in the context of cell ploidy.

Animals↗

Effects of a high-fiber diet on hepatocyte apoptosis and liver regeneration after partial hepatectomy in rats with fatty liver.

BACKGROUND: The morbidity and mortality that accompany fatty liver may occur as a result of increased apoptosis of hepatocytes and decreased liver regeneration. We determined the effects of a high-fiber diet on hepatocyte apoptosis and liver regeneration after partial hepatectomy in rats with fatty liver. METHODS: Fatty liver was induced in male Wistar rats weighing around 200 g through feeding of a high-fat diet for 4 weeks. The rats were then randomly assigned to 3 groups that received a high-fat diet, a normal diet, or a high-fiber diet for another 4 weeks. Partial hepatectomy (around 70%) was performed, and rats were killed 6, 24, 48, or 72 hours after hepatectomy. We then measured (1) the ratio of remnant liver weight to body weight and assessed the histology of the remnant liver as indicators of fatty liver, (2) caspase-3 activity and in situ cell death detection of DNA fragmentation as indicators of apoptosis, and (3) 5-bromo-2-deoxyuridine (BrdU) activity and (4) ornithine decarboxylase (ODC) contents in remnant livers as markers of regeneration. RESULTS: We found that (1) a high-fat diet for 4 weeks can markedly induce fatty liver, (2) apoptosis of hepatocytes is greater in fatty liver than in normal liver (98 +/- 19 vs 36 +/- 7) at 6 hours after partial hepatectomy (p < .05), (3) the capacity of liver regeneration decreases significantly (BrdU index: 30 +/- 5 vs 12 +/- 3, and ODC contents: 604 +/- 48 vs 390 +/- 42 mg/dL) in fatty liver 24 hours after partial hepatectomy (p < .05), (4) a normal diet can partially reverse the effects of fatty liver; (5) a high-fiber diet can significantly reverse the effects of fatty liver (p < .05). CONCLUSIONS: A high-fiber diet can reverse the negative effects of fatty liver on apoptosis and regenerative capacity after partial hepatectomy.

Animals↗

Effect of hyperbaric oxygenation on the regeneration of the liver after partial hepatectomy in rats.

The aim of the present study was to assess the influence of hyperbaric oxygenation (HBO) on rat liver regeneration before and after partial hepatectomy. Rats were sacrificed 54 h after 15% hepatectomy, liver and body weights were measured, and serum alanine transaminase (ALT) and aspartate transaminase (AST) activity and albumin levels were determined. The lipid peroxide level, as indicated by malondialdehyde production in the remnant liver was measured, and liver sections were analyzed by light microscopy. Five groups of 10 rats in each group were studied. The preHBO and pre-hyperbaric pressure (preHB) groups were treated before partial hepatectomy with 100% O2 and 21% O2, respectively, at 202,650 pascals, daily for 3 days (45 min/day). The control group was not treated before partial hepatectomy and recovered under normal ambient conditions after the procedure. Groups postHBO and postHB were treated after partial hepatectomy with HBO and HB, respectively, three times (45 min/day). The preHBO group presented a significant increase in the initiation of the regeneration process of the liver 54 h postoperatively. The liver/body weight ratio was 0.0618 +/- 0.0084 in the preHBO compared to 0.0517 +/- 0016 g/g in the control animals (P = 0.016). In addition, the preHBO group showed significant better liver function (evaluated by the lowest serum ALT and AST activities, P = 0.002 and P = 0.008, respectively) and showed a significant decrease in serum albumin levels compared to control (P < 0.001). Liver lipid peroxide concentration was lowest in the preHBO group (P < 0.001 vs control and postHBO group) and light microscopy revealed that the composition of liver lobules in the preHBO group was the closest to normal histological features. These results suggest that HBO pretreatment was beneficial for rat liver regeneration after partial hepatectomy.

Alanine Transaminase↗