Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Temporary portal triad clamping (Pringle maneuver) during liver resection reduces intraoperative blood loss. A normal liver can safely tolerate normothermic ischemia for up to 60 min. However, its safety in patients with surgical obstructive jaundice (SOJ) is not known. Therefore, we investigated the effect of hepatic ischemia in an experimental rat model of SOJ created by ligating the bile duct. Four groups of rats were created: Group I (sham operation, 10 days later, liver resection); Group II (sham operation, 10 days later, liver resection with 5 min of hepatic ischemia); Group III (bile duct ligation, 10 days later, liver resection); and Group IV (bile duct ligation, 10 days later, liver resection with 5 min of hepatic ischemia). The ischemic injury was assessed by the survival of rats, liver tissue malondialdehyde and total glutathione (markers of free radical injury), serum alanine aminotransferase, aspartate aminotransferase, and liver histology. The results showed decreased survival (47.6% vs. 90% [p = .046]), increased liver tissue malondialdehyde (161 +/- 35 vs. 129 +/- 33 microg/gm liver tissue [p = .05]), and decreased liver tissue total glutathione (565 +/- 169 vs. 1075 +/- 276 nmol/gm liver tissue [p = .05]) in rats with SOJ subjected to hepatic ischemia when compared to nonjaundiced rats. The changes in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase showed an increasing trend in the SOJ group but were not statistically significant. Ischemic changes in liver histology were seen more often in the SOJ group but were not statistically significant. These data suggest that temporary portal triad clamping in an experimental model of SOJ is detrimental to the outcome of liver resection.
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PMID:Evaluation of Pringle maneuver during liver resection in a rat model of surgical obstructive jaundice. 1603 81

Expression of intracellular adhesion molecule-1 (ICAM-1) in an obstructive jaundice model and the potential protective role of platelet activating factor antagonist over small intestine and liver together with its effects on bacterial translocation are examined in this study. Forty-eight male Wistar albino rats were assigned into four equal groups of 12. In groups I and II, animals were sham operated. In groups III and IV, common bile duct ligation and division were performed. In group I and group III, 0.5 ml/day normal saline was applied intraperitoneally daily from day 2 to 6 of the study; in group II and group IV, 1 mg/kg/day BN 52021 was applied intraperitoneally daily from day 2 to 6 of the study. All animals were sacrificed on postoperative day 7. ICAM-1 expression (CD54 positivity) was analyzed in the liver and ileum tissue by immunohistochemical method. Samples from blood, liver mesenteric lymph nodes, and spleen were cultured under aerobic conditions. It is revealed that ICAM-1 expression was statistically higher in group III, with highest bacterial translocation and liver and spleen injury when compared to other groups. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyltranspeptidase (GGT), bilirubin, tumor necrosis factor alpha (TNFalpha), and interleukin 1beta(IL-1beta) values were at the highest level in group III, and there was a statistical decrease in group IV compared to group III. The administration of BN52021 in experimental obstructive jaundice is a useful way to reduce liver and intestinal mucosal villi damage by inhibiting bacterial translocation and systemic inflammatory response.
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PMID:The effect of platelet activating factor antagonist BN 52021 on bacterial translocation and ICAM-I expression in experimental obstructive jaundice. 1624 68

Inhibitors of 3-hydroxy-3methylglutarly coenzyme A, reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. In ex vivo and in vitro studies, statins have antioxidative and antiinflammatory effects. Herein, we sought to determine whether treatment with fluvastatin (FV) would be beneficial in a rat model of common bile duct ligation (BDL)-induced liver injury. Female rats were subjected to a sham (n=10) or BDL (n=20). Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Three days after operation, rats subjected to CBDL were randomized to receive treatment with either FV (10 mg/kg) or saline every day over a 10 days experimental period. High levels of alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase decreased significantly (P<0.05) in animals treated with FV with compared to saline-administrated BDL animals. Compared with sham-operated rats, CBDL rats showed significantly higher levels of total nitrite and nitrate, malondihaldehyde, tumor necrosis factor alpha, myeloperoxidase, and lower concentrations of glutathione, superoxide dismutase, and catalase in the liver tissue (P<0.001). All of these changes were significantly attenuated (P<0.05) by treatment with FV after CBDL. CBDL was associated with increased apoptosis and nuclear factor kappa beta expression in saline-treated rats. Treatment with FV also decreased these parameters. These data support the view that FV ameliorates hepatic inflammation, lipid peroxidation, and tissue injury in rats subjected to CDBL. FV warrants further evaluation as an adjunctive treatment to ameliorate liver injury from extrahepatic biliary obstruction.
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PMID:Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis. 1708 24

To elucidate the roles of enteric bacteria and immunological interactions among liver, spleen and intestine in the pathogenesis of liver injury during obstructive jaundice, we studied the effects of antibiotics and splenectomy on bile-duct-ligated C57BL mice. When animals were subjected to bile-duct-ligation (BDL), plasma levels of bilirubin, alanine aminotransferase and aspartate aminotransferase increased markedly. However, the increases in plasma transaminases were significantly lower in splenectomized or antibiotics-treated groups than in the control BDL group. Histological examination revealed that liver injury was also low in the two groups. BDL markedly increased plasma level of interferon-gamma (IFN-gamma) and the expression of inducible nitric oxide synthase (iNOS) in liver and spleen. These changes were suppressed either by splenectomy or administration of antibiotics. Kinetic analysis revealed that BDL-induced liver injury and the increase of interleukin-10 (IL-10) and INF-gamma were lower in iNOS(-/-) than in wild type animals. BDL markedly increased the expression of IgA in colonic mucosa. These observations suggest that enteric bacteria, nitric oxide and cytokines including IFN-gamma and IL-10 derived from spleen and intestines form a critical network that determines the extent of liver injury during obstructive jaundice.
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PMID:Mechanism of Liver Injury during Obstructive Jaundice: Role of Nitric Oxide, Splenic Cytokines, and Intestinal Flora. 1839 95

Bile duct obstruction is associated with hepatic accumulation of leukocytes and liver injury. Emerging data suggest that platelets may play an important role in tissue damage and inflammation. Herein, we characterized the platelet response in cholestatic liver injury and evaluated the role of Rho-kinase signaling. For this purpose, C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 (10 mg/kg) and vehicle before undergoing bile duct ligation (BDL) for 12 h. Platelet rolling and adhesion, formation of platelet aggregates as well as microvascular perfusion in the liver were analyzed using intravital fluorescence microscopy. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Administration of Y-27632 reduced the BDL-associated increase of ALT and AST by 95% and 89%, respectively. The inhibition of Rho-kinase also reduced cholestasis-induced platelet rolling and adhesion by more than 46% and 73% in postsinusoidal venules and platelet adhesion in sinusoids by 60%. In addition, Y-27632 decreased platelet aggregation in hepatic sinusoids and postsinusoidal venules by 69% and 81%. BDL caused a significant reduction of hepatic microvascular perfusion. Importantly, pretreatment with Y-27632 restored sinusoidal perfusion in cholestatic animals. Our findings demonstrate that Rho-kinase regulates multiple aspects of platelet interaction in the microcirculation of cholestatic animals. Moreover, inhibition of Rho-kinase signaling not only attenuates platelet responses but also maintains microvascular perfusion and protects against hepatocellular injury in cholestasis. Thus, targeting Rho-kinase signaling may be an effective way to protect against platelet-mediated liver injury in obstructive jaundice.
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PMID:The Rho-kinase inhibitor Y-27632 inhibits cholestasis-induced platelet interactions in the hepatic microcirculation. 1937 10

We aimed to investigate the ameliorating effect of dehydroepiandrosterone (DHEA) on the potential hepatocellular damage in experimental obstructive jaundice. Twenty-four male rabbits in the study were randomly allocated into three groups. In the sham group, the choledochal canal was identified and explored. In the obstructive jaundice and treatment groups, the choledochal canal was ligated. Placebo and DHEA were administered to the obstructive jaundice and treatment groups, respectively. Blood samples were obtained at baseline, and both blood samples and liver tissue samples were obtained by re-laparotomy performed on day 8. Biochemical parameters were measured in blood samples, and liver samples were histopathologically evaluated. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP) and bilirubin levels were lower in the treatment group than in obstructive jaundice. Mononuclear inflammation in the portal region and hepatocyte degeneration were milder in the treatment group compared to obstructive jaundice group. Fibrosis and necrosis were also recovered by the DHEA treatment.In conclusion, these findings suggested that DHEA may reduce the obstructive jaundice-induced hepatocellular damage.
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PMID:Dehydroepiandrosterone ameliorates hepatocellular damage in obstructive jaundice. 2080 8

Ellagic acid (EA) is a natural polyphenolic compound. Although, modulator effects of EA on copper (Cu) and zinc (Zn) levels in some liver diseases have been reported in experimental animals, its effects in obstructive jaundice (OJ) has not been clarified. We aimed to evaluate potential effects of EA on Cu and Zn levels in liver and serum of cholestatic rats. Forty Wistar albino rats were equally divided into four groups. First group was used as controls. Second group received EA (60 mg(-1) kg(-1) day(-1)) for 8 days. Third was OJ group, and fourth group was OJ plus EA group. After 8 days, blood and liver samples were obtained. Higher serum and liver Cu and lower serum and liver Zn levels were found in OJ group (p < 0.05) compared with other groups. However, these differences reached to significant levels for Cu in serum and for Zn in lever. Higher serum copper levels were decreased, and lower liver Zn levels were increased by EA treatment in cholestatic rats (p < 0.05). Also, higher Cu/Zn ratio in OJ group was decreased by EA treatment both in liver (p < 0.05) and in serum (p < 0.05). Significantly higher serum bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase values were found in OJ and OJ + EA groups compared with the control and EA groups (p < 0.05). In conclusion, result of the current study indicated that ellagic acid has modulator effects on Cu and Zn levels in liver and serum of cholestatic rats.
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PMID:Effects of ellagic acid on copper, zinc, and biochemical values in serum and liver of experimental cholestatic rats. 2088 64

Serum levels of leucine amino peptidase (LAP) was studied along with bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and the ratio of AST/ALT and GGT/AST in 25 healthy subjects and 52 patients with hepatobiliary malignancies of which 12 were with hepatocellular carcinoma, 12 with liver metastasis, 6 with obstructive jaundice, 9 with carcinoma of gall bladder, 6 with carcinoma of pancreas and 7 with periampullary carcinoma. 24 Of the 52 patients studied had jaundice and 28 were without jaundice.LAP as compared to the other enzymes AST, ALT, GGT, ALP and AST/ALT ratio and GGT/AST ratio showed 100% elevation in obstructive jaundice, carcinoma of gall bladder and pancreas and periampullary carcinoma, 91.7% elevation in hepatocellular carcinoma and 83.3% elevation in liver metastasis. On comparing the levels of these enzymes in non jaundiced and jaundiced groups, LAP was elevated in both jaundiced and non jaundiced groups in 95.8% and 92.9% cases respectively whereas the other enzymes AST showed increase from 67.9% to 100%, ALT from 21.4% to 83.3%, GGT from 71.4% to 95.4% and ALP from 82.1% to 100% in non jaundiced and jaundiced groups respectively indicating that LAP rises in hepatic dysfunction due to hepatobiliary malignancy whereas the other liver function enzymes showed increased hepatic dysfunction due to hepatobiliary malignancy with the onset of jaundice thereby indicating that LAP is a better indicator of hepatobiliary malignancy as compared to other enzymes.The quantitative methods used for determination are reliable, accurate, simple, rapid and cost effective and therefore have better application in a clinical setting.
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PMID:Leucine amino peptidase a better indicator of carcinoma of liver, biliary tract and pancreas. 2310 93

Fasciola hepatica is an endemic zoonotic disease in Turkey and neighboring countries. The usual definitive host is the sheep; humans are accidental hosts in the life cycle of the Fasciola. There are two disease stages: the hepatic (acute) and biliary (chronic) stages. When the flukes enter the bile ducts, the symptoms of cholestasis and cholangitis may present, which can easily be misdiagnosed as obstructive jaundice of other causes. We present a case of fascioliasis, which was difficult to differentiate from cholangiocarcinoma. A 47-year-old woman from Eastern Turkey presented with fever, right upper quadrant abdominal pain, and jaundice. Total bilirubin was 4.2 mg/dl, aspartate aminotransferase 55 IU/L, alanine aminotransferase 65 IU/L, alkaline phosphatase 325 IU/L, and gamma-glutamyl transpeptidase 172 IU/L. All tumor markers including carcinoembryonic antigen and Ca19-9 were in normal values. After extended evaluation, an explorative laparotomy with cholecystectomy, choledochostomy and T-tube drainage was performed. Multiple flukes were removed from the choledochus. One of the parasites was sent to the parasitological clinic for identification. The result of an indirect hemagglutination test for F. hepatica was 1/320 (+). In conclusion, the chronic phase of this zoonotic infection can be easily misdiagnosed as any other cause of obstructive jaundice. Thus, F. hepatica should be considered in the differential diagnosis of common bile duct obstruction, especially in endemic areas.
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PMID:A rare cause of obstructive jaundice: Fasciola hepatica mimicking cholangiocarcinoma. 2316 10

The etiology and epidemiology of obstructive jaundice in Continental Croatia has been studied in 174 patients. The objective of this research was also to explore the importance and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) as a non-surgical method of treatment of obstructive jaundice in the population of Continental Croatia. Obstructive jaundice is the illness of elderly population which is also confirmed by the information on the average age of our patients. The frequency of illness is higher among female population, and the most frequent cause of obstructive jaundice are gallstones (54.1% of patients). In 29.8% of patients the primary or secondary malignant disease was the cause of blockage in gall flow and subsequent jaundice, and the most frequent malignant cause of obstructive jaundice is pancreas cancer in 11.5% of patients. The mean value of serum concentrations of total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and gamma glutamiltransferase 24 hours before the biliary decompression by ERCP has been significantly above the upper referential value, and 24 hours after the ERCP it has dropped to normal with their statistically significant difference (p < 0.0001). The normal values of markers for synthetic liver function (total proteins and prothrombin time) have been noticed as well as elevated values of inflammatory markers in obstructive jaundice independently of etiology. Out of the total number of patients, 37.7% required the surgical treatment while 60.3% of patients were treated by ERCP, i.e. either the stone extraction or the implantation of endobiliary stent was performed.
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PMID:Etiology and epidemiology of obstructive jaundice in Continental Croatia. 2369 62


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