Melatonin regulates L-arginine transport and NADPH oxidase in young rats with bile duct ligation: role of protein kinase C.

BACKGROUND: Bile duct ligation (BDL) is a commonly used cholestatic liver disease (CLD) model. We recently found that L-arginine levels were significantly raised by melatonin in young rats with BDL. We hypothesized that protein kinase C-α (PKC-α) is involved in the increases of L-arginine in melatonin-treated BDL rats. In addition, we tested whether melatonin prevents nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-induced reactive oxygen species (ROS) production, in rats with BDL, through PKC. METHODS: Four groups of young male rats were studied: shams (n = 6), untreated BDL rats (n = 9), melatonin-treated shams (n = 6, M), and melatonin-treated BDL rats (n = 6, BDL + M). Melatonin-treated rats received daily melatonin 1 mg/kg/d via i.p. injection. All surviving rats were killed 14 d after surgery. RESULTS: Melatonin prevented BDL-induced mortality and kidney injury. Melatonin additionally increased L-arginine concentrations in BDL liver, which is correlated with decreased PKC-α translocation. Next, melatonin increased L-arginine levels in BDL kidneys, which was correlated with decreased renal levels of arginase II. In the BDL kidney, melatonin decreased PKC-ß translocation, reduced p47phox translocation, and diminished NADPH-dependent superoxide production. CONCLUSION: Melatonin inhibits PKC-α to increase cationic amino acid transporter-1 (CAT-1)-mediated L-arginine uptake in BDL liver, whereas it inhibits PKC-ß to reduce NADPH-dependent superoxide production.

Effects of albumin administration in serum liver enzymes of rats in the presence of extrahepatic biliary obstruction.

PURPOSE: To study the influence of albumin on changes of liver function in the extrahepatic biliary obstruction through an experimental model in rats. METHODS: Sixty rats were divided into four groups: Group C (Control): 6 animals. Group M (Fictitious Operation): 18 rats underwent laparotomy and handling of the bile ducts; Groups O (extrahepatic biliary obstruction) and A (Treated with 2% albumin): 18 animals in each group underwent ligation of the ductus liver; The animals in groups M, O and A were divided into three subgroups of 6 animals each to be killed in the 7, 14 and 21 days postoperative (POD). Blood was drawn for determination of total bilirubin (TB), indirect bilirubin (IB), direct bilirubin (DB), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: On POD 7, BI levels were 4.5 mg / dl in group O and 2.1 mg / dl in group A (p = 0.025). On the 14th POD, the levels of PA were 1185.2 U / l in the group and O 458.3 U / l in group A (p = 0.004). ALT levels were 101.7 U / l in the group O and 75.7 U / l in group A (= 0.037). On POD 21, the levels of ALP were 1069.5 U / l in the group O and 468.3 U / l in group A (p = 0, 004). CONCLUSION: The administration of albumin reduced the serum levels of bilirubin in the 7th day of supplementation.

Effects of albumin administration in serum liver enzymes of rats in the presence of extrahepatic biliary obstruction / Efeitos da administração de albumina nos níveis séricos de enzimas hepáticas em ratos com obstrução biliar extra-hepática

PURPOSE: To study the influence of albumin on changes of liver function in the extrahepatic biliary obstruction through an experimental model in rats. METHODS: Sixty rats were divided into four groups: Group C (Control): 6 animals. Group M (Fictitious Operation): 18 rats underwent laparotomy and handling of the bile ducts; Groups O (extrahepatic biliary obstruction) and A (Treated with 2 percent albumin): 18 animals in each group underwent ligation of the ductus liver; The animals in groups M, O and A were divided into three subgroups of 6 animals each to be killed in the 7, 14 and 21 days postoperative (POD). Blood was drawn for determination of total bilirubin (TB), indirect bilirubin (IB), direct bilirubin (DB), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: On POD 7, BI levels were 4.5 mg / dl in group O and 2.1 mg / dl in group A (p = 0.025). On the 14th POD, the levels of PA were 1185.2 U / l in the group and O 458.3 U / l in group A (p = 0.004). ALT levels were 101.7 U / l in the group O and 75.7 U / l in group A (= 0.037). On POD 21, the levels of ALP were 1069.5 U / l in the group O and 468.3 U / l in group A (p = 0, 004). CONCLUSION: The administration of albumin reduced the serum levels of bilirubin in the 7th day of supplementation.

OBJETIVO: Estudar a influência da albumina em alterações funcionais do fígado na obstrução biliar extra-hepática por meio de um modelo experimental desenvolvido em ratos. MÉTODOS: 60 ratos distribuídos em quatro grupos: Grupo C (Controle): 6 animais. Grupo M (Operação Fictícia): 18 ratos submetidos à laparotomia e manuseio das vias biliares; Grupos O (Obstrução Biliar Extra-hepática) e A (Tratados com albumina a 2 por cento): 18 animais, em cada grupo, submetidos à ligadura do ducto hepático; Os animais dos grupos M, O e A foram distribuídos em três subgrupos de 6 animais cada, para serem mortos nos 7°, 14° e 21° dias pós- operatórios (DPO). Foi colhido sangue para dosagem de bilirrubina total (BT), bilirrubina indireta (BI), bilirrubina direta (BD), fosfatase alcalina (FAL), aspartato aminotransferase (AST) e alanina aminotransferase (ALT). RESULTADOS: no 7º DPO, os níveis de BI foram 4,5 mg/dl no grupo O e 2,1mg/dl no grupo A (p=0,025). No 14º DPO, os níveis de FAL foram 1185,2 U/l no grupo O e 458,3 U/l no grupo A (p=0,004). Os níveis de ALT foram de 101,7 U/l no grupo O e 75,7 U/l no grupo A (=0,037). No 21º DPO, os níveis de FAL foram de 1069,5 U/l no grupo Oe de 468,3 U/l no grupo A (p =0, 004). CONCLUSÃO: a administração de albumina reduziu os níveis séricos de bilirrubina indireta no 7°dia de suplementação.

Effect of L-arginine on metabolism of polyamines in rat's brain with extrahepatic cholestasis.

Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of L-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with L-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with L-arginine. Increased plasma gamma-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of L-arginine (P < 0.001). Cholestasis increased the brain's putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of L-arginine in BDL rats prevents metabolic disorders of polyamines and establishes a neuroprotective role in the brain during cholestasis.

Metabolic changes in rat brain histaminergic neurons during subhepatic cholestasis.

The aim of the present work was to assess metabolic changes in histaminergic neurons in the rat brain during subhepatic cholestasis. Studies were performed on male Wistar rats using quantitative histochemical methods. The results showed that in cholestasis, histaminergic neurons in the rat hypothalamus developed significant changes in succinate dehydrogenase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase activity, in NADH and NADPH, and in acid phosphatase and monoamine oxidase B. These changes depended on the duration of cholestasis and had a dynamic, wave-like nature. The changes were apparent after five days of cholestasis, reached a maximum at 10-20 days, decreased at 45 days, and completely disappeared at 90 days.

[Analysis of tear enzymes in the diagnosis of obstructive jaundice associated with subhepatic cholestasis].

The activity of enzymes, such as alkaline phosphatase, gamma-glutamyl transpeptidase, and leicine aminopeptidase, was found to be increased in the serum and tear of 28 patients with obstructive jaundice. In malignant tumor-induced jaundice, the activity of the enzymes, the indicators of cholestasis, was higher than that in obstructive jaundice caused by extrahepatic bile duct calculi. A new method has been devised for noninvasive diagnosis of obstructive jaundice from tear enzyme immunoassay. The method is simple, reliable, and usable at a clinical laboratory.

Effects of lexipafant (BB-882), a platelet activating factor receptor antagonist, on liver damage due to bile duct ligation in rats.

BACKGROUND AND STUDY AIMS: Extrahepatic cholestasis is one of the main factors causing liver fibrosis. In this study, we aimed to evaluate the effects of lexipafant (BB-882), a platelet activating factor receptor antagonist, on liver damage in rats with bile duct ligation. METHODS: A total of 30 male Sprague-Dawley rats weighing 160-190 g were used in this study. Group 1 (Sham-control, n = 10) rats were undergone laparotomy alone and bile duct was just dissected from the surrounding tissue. Group 2 rats (BDL/Untreated, n = 10) were subjected to bile duct ligation and no drug was applied. Group 3 rats (BDL/BB-882, n = 10) received a daily dose of BB-882 intraperitoneally for 14 days after BDL. At the end of the two-week period, biochemical and histological evaluation was processed. RESULTS: The mean serum bilirubin and liver enzymes level significantly decreased, and Superoxide dismutase, catalase and glutathione peroxidase values were significantly increased in BDL/BB-882 group when compared to BDL/Untreated group. The histopathological score was significantly less in the BDL/BB-882 group compared to the BDL/Untreated rats. In the BDL/BB-882 group was observed less fibrosis and neutrophil infiltration CONCLUSIONS: These results suggest that BB-882 (lexipafant) may reduce the severity of the inflammatory response to liver injury produced by bile duct ligation in rats.

Serum gamma glutamyl transferase activity in horses with right or left dorsal displacements of the large colon.

The purpose of this study was to test the hypothesis that horses with right dorsal displacement of the large colon (RDDLC) have elevations in serum gamma glutamyl transferase (GGT) activity when compared with horses with left dorsal displacement of the large colon (LDDLC). Medical records from 37 horses with RDDLC and 48 horses with LDDLC were reviewed. Horses were included for study if the RDDLC or LDDLC was confirmed by exploratory laparotomy or postmortem examination and if a serum GGT measurement was obtained within 24 hours before surgery. The proportion of horses with GGT activity within or above the reference range was determined. Of 37 horses, 18 (49%; exact binomial 95% confidence interval, 32-66%) with RDDLC and, of 48 horses, 1 (2%; 95% CI, 0-11%) with LDDLC had GGT above the reference range. Horses with RDDLC had higher serum GGT than did horses with LDDLC. Of 37 horses, 36 (97%) with RDDLC were discharged with a good prognosis and none returned as a result of hepatic disease. Evaluation of surgical and postmortem examinations revealed that positioning of the colon in horses with RDDLC results in compression of the bile duct, which can cause extrahepatic bile duct obstruction and a subsequent elevation in serum GGT activity.

Protective effect of IGF-1 on experimental liver cirrhosis-induced common bile duct ligation.

BACKGROUND/AIMS: The causes of malnutrition in liver cirrhosis are multifactorial. Levels of IGF-1 (insulin like growth factor-1) that is a crucial regulator of intermediary metabolism decreases. The aim of this study was to analyze the effect of IGF-1 supplementation during liver cirrhosis induced by common bile duct ligation. METHODOLOGY: Rats were divided into five different groups: One sham and four experimental groups. Rats in three of four groups were treated with 2 micrograms/day IGF-1 with a different time of experiment in each group. Blood biochemical parameters, tissue malondialdehyde, glutathione levels and the activity of tissue antioxidant enzymes and conventional and immunohistochemical analysis of liver samples were studied for each group. RESULTS: Serum albumin, total protein, fibrinogen levels decreased and prothrombin time was prolonged in the bile duct ligated and transected experimental group but not in the IGF-I treated rats compared with the rats in sham group. Liver malondialdehyde levels significantly increased in control group but not in IGF-1 treated groups. The activities of antioxidant enzymes were decreased compared with the other groups. Histopathology findings of liver biopsy demonstrated intense degree fibrosis and overexpression of fibroblast growth factor and desmin in the control group but a lesser degree of those in the IGF-1 treated groups. CONCLUSIONS: IGF-1 treatment improves liver function and decreases oxidative liver damage and histopathological findings. Further studies are required to delineate the mechanisms of protective effects of IGF-1.

Low enzyme content in the pancreas does not reduce the severity of acute pancreatitis induced by bile-pancreatic duct obstruction.

Enzyme load in pancreas has been considered a risk factor in the development of acute pancreatitis. In order to confirm this hypothesis our aim was to analyze the development and evolution of acute pancreatitis (AP) induced by bile-pancreatic duct obstruction (BPDO) after reducing the pancreatic enzyme content. L-364,718 - a potent CCK-receptor antagonist - was administered (0.1 mg/kg/day) for 7 days before inducing AP by BPDO. The course of AP was evaluated at different times from 1.5-48 h after BPDO. Amylase and trypsinogen contents and cytosolic calcium levels were measured by flow cytometry using specific antisera against pancreatic enzymes labelled with isothiocyanate of fluorescein and Fluo 3, respectively. The severity of the disease at the different stages was evaluated by measurements of amylase activity in ascites and plasma, percentage of pancreatic fluid and haematocrit. Electron microscopy study of the pancreas showed an increased number of zymogen granules spread through the acinar cells of control rats treated with L-364,718 for 7 days, however, total enzyme content in individual acinar cells was significantly (p < 0.01) diminished. AP significantly increased intracellular amylase and trypsinogen load from 3-12 h after BPDO, and prior L-364,718 treatment enhanced the blockade of enzyme secretion. As a result, acinar enzyme content was significantly increased from earlier stages (1.5 h after BPDO). In parallel, increased cytosolic calcium levels observed up to 24 h after BPDO appeared earlier in L-364,718-treated rats than in those not treated. The severity of AP seems to have been higher in rats previously treated with the CCK-receptor antagonist as indicated by the significantly higher pancreatic fluid and amylase activity in ascites and plasma observed at different times after BPDO. Our results indicate that there is no correlation between the severity of pancreatitis and the amount of enzymes accumulated in the pancreas before the disease is induced.

Differential expression of canalicular membrane Ca2+/Mg(2+)-ecto-ATPase in estrogen-induced and obstructive cholestasis in the rat.

Extracellular adenosine triphosphate (ATP) may regulate hepatocyte and cholangiocyte functions, and under some conditions it may have deleterious effects on bile secretion and cause cholestasis. The canalicular membrane enzyme Ca2+/Mg2+-ecto-ATPase (ecto-ATPase) hydrolyzes ATP/adenosine diphosphate (ATP/ADP) and regulates hepatic extracellular ATP concentration. Changes in liver ecto-ATPase in estrogen-induced cholestasis were examined in male rats receiving 17alpha-ethinylestradiol (E groups) for 1, 3, or 5 days (5 mg/kg/day, sc) and compared with changes in rats subjected to obstructive cholestasis (O groups) for 1, 3, or 8 days. Activity of ecto-ATPase, protein mass in canalicular membranes and bile (estimated by Western blotting), steady state mRNA levels (by Northern blotting), and cellular and acinar distributions of the enzyme (histochemistry and immunocytochemistry) were assessed in these groups. Activity of ecto-ATPase, protein mass in isolated canalicular membranes, and enzyme mRNA levels were significantly increased in E group rats as compared with controls. In contrast, these parameters were markedly decreased in O group rats, and the enzyme protein was undetectable in bile. The ecto-ATPase histochemical reaction was markedly increased in the canalicular membrane of E group rats, extending from acinar zone 2 to zone 1, whereas it decreased in the O group. The ecto-ATPase immunocytochemical reaction was present in the canalicular membrane and pericanalicular vesicles in control and E group hepatocytes, but it decreased in obstructive cholestasis and was localized only to the canalicular membrane. Thus, significant changes in liver ecto-ATPase were apparent in 17alpha-ethinylestradiol-induced cholestasis that were opposite to those observed in obstructive cholestasis. Assuming that the alterations observed in obstructive cholestasis are the result of the cholestatic phenomenon, we conclude that changes in ecto-ATPase in 17alpha-ethinylestradiol-treated rats might be either primary events or part of an adaptive response in 17alpha-ethinylestradiol-induced cholestasis.

Effects of obstructive jaundice on the antioxidative capacity of human red blood cells.

Transient haemolysis and shortened erythrocyte lifespan are reported in association with extrahepatic biliary tract obstruction. An increase in lipid peroxidation has been noted as evidence of oxidative damage in red cells due to cholestasis. The influence of surgical relief on the antioxidative capacity of the erythrocyte is less well defined. The ability of erythrocytes to regenerate the antioxidative capacity after side-to-side choledo-choduodenostomy was assessed by measuring the two principal antioxidant enzymes, namely superoxide dismutase (SOD) and catalase (CAT), as well as the glutathione (GSH) content in the red blood cells (RBC) taken from patients with obstructive jaundice. A comparison of patients and healthy volunteers revealed a consistent decrease in enzyme activities (pSOD = 0.01, pCAT = 0.0002) and glutathione concentrations (PGSH = 0.0000) in cholestatic patients. Statistical analysis proved a clear correlation between the surgical relief of common bile duct obstruction and restored antioxidative capacity of red cells. These observations suggest that the red cells from patients with multiple common bile duct stones almost completely regenerated their antioxidative capacity four weeks after side-to-side choledochoduodenostomy.

Respective value of alkaline phosphatase, gamma-glutamyl transpeptidase and 5' nucleotidase serum activity in the diagnosis of cholestasis: a prospective study of 80 patients.

We studied the value of alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), and 5'-nucleotidase (5'-NU) activities in the diagnosis of intrahepatic (IHC) versus extra-hepatic cholestasis (EHC). Eighty patients were included prospectively. All presented with cholestasis as defined by a concomitant increase in at least two of three cholestatic enzymes (AP, GGT, 5'-NU), a low cytolytic ratio (alanine aminotransferase/AP [xN/xN] < or = 5), and no evidence for associated liver tumor. We compared 43 patients with IHC due to chronic liver disease to 37 patients with EHC due to main bile duct obstruction. Fasting blood samples for activity determination (AP, GGT, 5'-NU) were taken before performing liver biopsy in cases of IHC and before endoscopic or surgical management in cases of EHC. Enzyme activities were compared using univariate and multivariate analysis. AP (276 IU/L [35-3,140] vs. 123 IU/L [37-699]: p < 0.0001), GGT (595 IU/L [98-5,200] vs. 211 IU/L [38-925]; p < 0.0001), and 5'-NU (32 IU/L [10-142] vs. 16 IU/L [4-107]: p < 0.0003) were significantly higher in EHC when compared to IHC. Only in GGT and 5'-NU activities were independent variables significantly linked to the mechanism of cholestasis. In IHC, the ratio GGT/5'-NU (xN/xN) was significantly lower than in EHC (2.8 [0.7-7.2] vs. 3.7 [1.8-10.5]: p < 0.006). A threshold of GGT/5'-NU < 1.9 had a sensitivity of 40% and a specificity of 100% for the diagnosis of IHC. Although such hepatobiliary enzymes cannot be regarded as diagnostic, they can provide useful information to orientate the clinician in the diagnosis of cholestasis.

Hepatic cytochrome oxidase in rats with microsurgical cholestasis or portocaval shunt.

AIMS: portocaval shunt and extrahepatic cholestasis are experimental models of chronic hepatic insufficiency of different etiology and histological characteristics, and which probably also differ in the mechanism of impairment of oxidative metabolism. To test this hypothesis we measured hepatic cytochrome oxidase. METHODS: cytochrome oxidase was assayed with a histochemical technique in three groups of Wistar rats: A (n = 8) control; B (n = 8) microsurgical extrahepatic cholestasis; and C (n = 8) end-to-side portocaval shunt. RESULTS: cytochrome oxidase activity was lowest in group B, both in the left middle (p = 0.00019) and in the inferior caudate (p = 0.00014) hepatic lobes, and was highest in group C in both hepatic lobes, especially in the left middle lobe (p = 0.0029). CONCLUSION: the decrease in cytochrome oxidase activity in the liver of rats with extrahepatic cholestasis and the increase in animals subjected to portal flow deprivation demonstrate the different nature of the impairment in hepatic oxidative metabolism in these two pathological conditions.

Morphological adaptations of human liver peroxisomes in cholestasis.

Part of the bile acid synthesis takes place in peroxisomes. An altered enterohepatic circulation of bile acids might influence peroxisomal beta-oxidation enzymes and peroxisomal morphology. We performed a morphological and morphometric investigation of peroxisomes in liver biopsy samples of eight patients with cholestasis of different origin: graft versus host reaction (n = 1), obstruction of the bile flow (n = 3), and drug-induced cholestatic hepatitis (n = 4). Peroxisomes were identified using catalase cytochemistry. They were regularly shaped and showed individual differences in electron density. A perinuclear distribution was observed in a variable number of hepatocytes in each sample. Morphometric analysis of peroxisomes revealed an increase in numerical density and surface density in all, and a decreased mean diameter in four liver samples. Based on previously obtained data in experimental animals, we hypothesize that the observed alterations in peroxisomal morphology indicate an enhanced metabolic activity of the enzymes in the peroxisomal matrix. Among them are enzymes involved in bile acid synthesis.

The role of oxygen free radicals in acute renal failure complicating obstructive jaundice: an experimental study.

Oxidant injury is considered to be an important mechanism in the pathophysiology of acute renal failure. It has been thought that decrease in extracellular and intracellular fluid and endotoxemia seen in obstructive jaundice may cause an increase in production of oxygen free radicals and impairment in antioxidant defense mechanism. This study is designed to investigate the possible role of oxidant injury in renal failure seen in jaundiced patients. In this study, 28 rats were divided into four groups: Control (C)(N = 7); Renal ischemia (RI)(N = 7); Obstructive jaundice+renal ischemia (OJ+RI)(N = 7); Obstructive jaundice (OJ)(N = 7). All groups were compared with each other according to renal failure findings and enzyme activities, such as Xanthine oxidase (XOD), Superoxide Dismutase (SOD) and Catalase in renal cortex and Glutathione Peroxidase (GSH-Px), in blood at 3rd day after ischemia and reperfusion. Renal failure findings monitored by blood urea and creatinine levels, seemed more evident in OJ+RI than RI group (p < 0.05). When compared with RI, in OJ+RI group, increase in XOD activity at 3rd day was statistically significant [0.259 +/- 0.01 U/g (tissue) and 0.362 +/- 0.03 U/g (tissue) respectively] (p < 0.05). SOD and GSH-Px activities of each ischemic group at 3rd day were decreased compared to non-ischemic groups. This fall was significant (p < 0.05). But there was no statistical difference between jaundiced and non-jaundiced groups. Alterations in catalase activities also had no statistical significance. These findings may suggest that the injury induced by oxygen free radicals at re-oxygenation of tissue after ischemia may also play a role in the pathogenesis of acute renal failure developed in obstructive jaundice.

"Significance of serum gamma glutamyl transpeptidase in cholestatic jaundice".

In conclusion, our study showed that serum G.G.T rises in cholestasis, and the rise is significantly higher in extraphepatic cholestasis as compared to intrahepatic cholestasis. Serum G.G.T has not shown any superiority over alkaline phosphatase in the evaluation of cholestatic liver disease. However, two considerations must caution against the use of serum G.G.T. alone for evaluation of hepatobiliary disease. The first of these is the lack of specificity for hepatobiliary disease. Serum G.G.T. activity can be elevated in some non-hepatic disorders such as acute pancreatitis, congestive cardiac failure, myocardial infarction, diabetes mellitus and alcoholism. Determination of serum G.G.T. in these patients is of no value. Second, the possibility that changes in serum G.G.T. activity results from drug administration in man.

[Consequences of cholestasis from the hepatologist's viewpoint]. / Konsequenzen der Cholestase aus der Sicht des Hepatologen.

Chronic cholestasis is associated with a variety of symptoms and dysfunction of most organs. Among them, jaundice and pruritus are the first to be recognized, usually prompting the patients to see a physician. Besides the skin, however, cholestasis also affects, inter alia, the metabolism of plasma lipids and fat-soluble vitamins, as well as bone and liver. In the following article the pathogenesis and therapy of metabolic disturbances and organ dysfunctions occurring frequently in patients with chronic cholestasis are discussed.

Aminotransferase levels in hypothermic preservation medium and liver mitochondrial function in acute extrahepatic biliary obstruction in rats

In acute extrahepatic biliary obstruction (AEBO), serum aminotransferase levels (ALT and AST) are similar to those observed in acute hepatitis (AH). Microscopically, the two pathologies have completely different characteristics, indicating the possibility that different mechanisms underlie the passage of aminotransferase from the intracellular to the intravascular medium. The objective of the present study was to assess serum ALT and AST levels in rats with AEBO and ALT and AST levels in preservation medium (PM) and the hepatic mitochondrial function before and after hypothermic (2-4ºC) liver preservation. Two sets of experiments were performed: The first set was conducted on 14 male Wistar rats (250-350g), 7 of them used as controls and 7 submitted to AEBO of 24-h duration. The second set was conducted on 14 male Wistar rats weighing 250-350 g divided into two groups of 7 animals, each, i. e., a control group (n=7) and an ischemic group. Before being submitted to hypotermic presevation, the animals were submitted to 1 hour of warm ischemia. After hepatectomy, the livers from all groups were preserved in Belzer UW solution at 2-4ºC for 3 h. The serum aminotransferase levels in the AEBO group were significantly increased to 1707 + 223 U/l for AST, 1522 + 45 U/l for ALT, and 1508 + 127 U/l for alkaline phosphatase when compared to the controls (P < 0.0001)...

[Development of biochemical and histopathological parameters in paracetamol overdose in experimental cholestasis]. / Evolución de parámetros bioquímicos e histopatológicos en la sobredosis con paracetamol durante la colestasis experimental.

The aim of the present paper is to determine the effect of Paracetamol (P) acute intoxication in cholestatic rats. Four groups of animals were considered: controls, controls intoxicated with P, rats intoxicated with P and cholestatic rats. Hepatic biochemical tests and liver histology were performed in every group. It is concluded that cholestatic rats intoxicated with P showed less Liver damage than in control groups.