Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholestasis is a major complication in sepsis although the underlying mechanisms remain elusive. The aim of this study was to evaluate the role of P-selectin and leukocyte recruitment in endotoxemia-associated cholestasis. C57BL/6 mice were challenged intraperitoneally with endotoxin (0.4 mg/kg), and 6 h later the common bile duct was cannulated for determination of bile flow and biliary excretion of bromosulfophthalein. Mice were pretreated with an anti-P-selectin antibody or an isotype-matched control antibody. Leukocyte infiltration was determined by measuring hepatic levels of myeloperoxidase. Tumor necrosis factor-alpha and CXC chemokines in the liver was determined by ELISA. Liver damage was monitored by measuring serum levels of alanine aminotransferase and aspartate aminotransferase. Apoptosis was quantified morphologically by nuclear condensation and fragmentation using Hoechst 33342 staining. Endotoxin induced a significant inflammatory response with increased TNF-alpha and CXC chemokine concentrations, leukocyte infiltration, liver enzyme release, and apoptotic cell death. This response was associated with pronounced cholestasis indicated by a >70% decrease of bile flow and biliary excretion of bromosulfophthalein. Immunoneutralization of P-selectin significantly attenuated endotoxin-induced leukocyte infiltration reflected by a >60% reduction of hepatic myeloperoxidase levels. Interference with P-selectin decreased endotoxin-mediated hepatocellular apoptosis and necrosis, but did not affect hepatic levels of tumor necrosis factor-alpha and CXC chemokines. Of interest, inhibition of P-selectin restored bile flow and biliary excretion of bromosulfophthalein to normal levels in endotoxin-challenged animals. Our study demonstrates for the first time that P-selectin-mediated recruitment of leukocytes, but not the local production of proinflammatory mediators, is the primary cause of cholestasis in septic liver injury.
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PMID:Sepsis-associated cholestasis is critically dependent on P-selectin-dependent leukocyte recruitment in mice. 1725 63

Mercury(II) is a highly toxic metal which induces oxidative stress in the body. In this study we aimed to investigate the possible protective effect of Ginkgo biloba (EGb), an antioxidant agent, against experimental mercury toxicity in rat model. Following a single dose of 5mg/kg mercuric chloride (HgCl(2); Hg group) either saline or EGb (150mg/kg) was administered for 5days. After decapitation of the rats trunk blood was obtained and the tissue samples from the brain, lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Formation of reactive oxygen species in the tissue samples was monitored by chemiluminescence (CL) technique. BUN, creatinin, ALT, and AST levels and tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) activity were assayed in serum samples. The results revealed that HgCl(2) induced oxidative damage caused significant decrease in GSH level, significant increase in MDA level, MPO activity and collagen content of the tissues. Treatment of rats with EGb significantly increased the GSH level and decreased the MDA level, MPO activity, and collagen contents. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the Hg group as compared to control group. On the other hand, EGb treatment reversed all these biochemical indices. Our results implicate that mercury-induced oxidative damage in brain, lung, liver, and kidney tissues protected by G. biloba extract, with its antioxidant effects.
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PMID:Ginkgo biloba extract protects against mercury(II)-induced oxidative tissue damage in rats. 1726 89

This study was designed to investigate the protective effect of oleanolic acid (OA) against isoproterenol-induced myocardial ischemia in rat myocardium. Wistar strain rats were pretreated with OA (20, 40, and 60 mg/kg, s.c) for 7 days and then intoxicated with isoproterenol (ISO, 85 mg/kg, sc for 2 consecutive days). Heart were excised from the experimental animals and assessed for the activities of marker enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK)], the levels of lipid peroxide products [thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD)], myeloperoxidase (MPO), lipid profiles [total cholesterol (TC), free cholesterol, ester cholesterol, triglycerides (TG), free fatty acids (FFA) and phospholipids (PL)], and membrane-bound ATPase enzymes (total ATPase, Na(+)K(+) ATPase, Ca(2 +) ATPase, and Mg(2 +) ATPase). Troponin T and I were estimated in plasma. Leakage of cardiac markers, elevated lipid peroxidation with increased lipid profiles and decreased activities of membrane-bound ATPase enzymes were confirmed the severe myocardial damage occurring as a consequence of isoproterenol-induced ischemia, and they also showed the significant improvement effected by oleanolic acid pretreatment. These findings provided evidence that oleanolic acid was found to be protecting rat myocardium against ischemic insult and the protective effect could attribute to its anti-oxidative, anti-hyperlipedemic, and anti-arrhythmic properties as well as its membrane-stabilizing action.
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PMID:Cardioprotective effect of oleanolic acid on isoproterenol-induced myocardial ischemia in rats. 1745 91

Severe burn induces the activation of an inflammatory cascade that contributes to the development of subsequent immunosuppression, increased susceptibility to sepsis, as well as generation of reactive oxygen radicals and lipid peroxidation, leading to multiple organ failure. In the present study, we investigated whether rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats were exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10s. Rosiglitazone (4 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn. Rats were decapitated 24h after injury and the tissue samples from lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and creatinine, blood urea concentrations (BUN) were determined to assess liver and kidney function, respectively. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and lactate dehydrogenase (LDH) were also assayed. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH, IL-1 beta and TNF-alpha were elevated in the burn group as compared to the control group. Rosiglitazone treatment reversed all these biochemical indices. According to the findings of the present study, rosiglitazone possesses a anti-inflammatory effect that prevents burn-induced damage in remote organs and protects against organ damage.
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PMID:Rosiglitazone, a PPAR-gamma ligand, protects against burn-induced oxidative injury of remote organs. 1746 12

This study was performed to investigate a novel strategy to pharmacologically inhibit high-mobility group box 1 protein (HMGB1) expression with sodium butyrate, a short-chain fatty acid. Using a sepsis model induced by cecal ligation and puncture (CLP), 100 male Wistar rats were randomly divided into 4 groups as follows: control group (10 rats), sham operation group (10 rats), CLP group (further randomized into 2, 6, 12, 24, 48, and 72 h post-CLP subgroups, each 10 rats), and sodium butyrate treatment group (further randomized into 12 and 24 h post-CLP subgroups, each 10 rats). Animals of all groups were killed at designated time points, and blood and tissue samples from livers, lungs, kidneys, and small intestines were harvested to determine organ damage-related variables, and HMGB1 mRNA expression was assessed by the reverse-transcription-polymerase chain reaction. In addition, we observed the effect of treatment with sodium butyrate on survival rate in septic rats. The results showed that early treatment with sodium butyrate can markedly reduce serum alanine aminotransferase, creatinine levels at 12 h, and pulmonary myeloperoxidase activity at 24 h post-CLP, and significantly improve the 1- to 6-day survival rates in animals subjected to CLP (P < 0.05-0.01). These findings suggest that HMGB1 is excessively expressed and produced in sepsis. Sodium butyrate can markedly inhibit HMGB1 mRNA expression and may have protective effect on multiple organ damage in sepsis.
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PMID:Sodium butyrate prevents lethality of severe sepsis in rats. 1750 8

We examined how oxidative stress and cell damage develop in the liver of rats subjected to water-immersion stress (WIRS). In rats subjected to WIRS for 1.5, 3 or 6 h, serum alanine aminotransferase and aspartate aminotransferase activities increased time-dependently. In the liver tissue, vacuolization and apoptosis occurred at 1.5 h of WIRS and vacuolization further developed without further appearance of apoptosis at 3 h or 6 h. Serum lipid peroxide (LPO) and NOx (nitrite/nitrate) concentrations increased at 3 h of WIRS and these increases were enhanced at 6 h. In liver tissue, increases in LPO and NOx concentrations and myeloperoxidase activity and decreases in ascorbic acid and reduced glutathione concentrations and superoxide dismutase activity occurred at 3 h of WIRS and these changes were enhanced at 6 h, although vitamin E concentration and xanthine oxidase activity were unchanged. These results indicate that oxidative stress in the liver of rats with WIRS develops after the appearance of cell damage in the tissue, and suggests that oxidative stress is caused through disruption of the antioxidant defense system and increases in NO generation and neutrophil infiltration in the liver, which may contribute to the progression of cell damage in the tissue.
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PMID:Development of oxidative stress and cell damage in the liver of rats with water-immersion restraint stress. 1762 21

The aim of this study was to investigate the influence of enalaprilat on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in a significant increase in the mortality rate, pancreatic necrosis, serum activity of amylase, alanine aminotransferase (ALT), and interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, and tissue activity of myeloperoxidase (MPO) and maondialdehyde (MDA) in the pancreas and lung, and a significant decrease in concentrations of calcium, blood pressure, urine output and p0(2). The use of enalaprilat inhibited the changes in urine output, blood pressure, serum concentration of urea, p0(2), and tissue activity of MPO and MDA in the pancreas and lungs. It reduced the mortality and pancreatic damage. Enalaprilat demonstrated a beneficial effect on the course of ANP in rats; therefore, it may be used in the treatment of acute pancreatitis.
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PMID:Effects of enalaprilat on acute necrotizing pancreatitis in rats. 1765 97

In this research, the role of leptin on sepsis-induced organ dysfunction was evaluated. Making use of a mice sepsis model, changes of alanine transaminase and uric acid in serum, myeloperoxidase activity, leptin levels and histological alterations in heart, lung, liver and kidney were determined. Results showed that sepsis induced significantly higher levels of serum alanine transaminase and uric acid, decreased tissue myeloperoxidase activity and leptin levels, and triggered distinct histological alterations. However, leptin and indomethacin injections reversed those impairments at 6h and/or 12h after injury. These data reveal a protective role of both leptin and indomethacin on vital organ functions after sepsis by recovering tissue myeloperoxidase activity.
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PMID:Leptin protects vital organ functions after sepsis through recovering tissue myeloperoxidase activity: an anti-inflammatory role resonating with indomethacin. 1768 5

Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (CIH) during sleep. OSA is associated with nonalcoholic steatohepatitis (NASH) in obese individuals and may contribute to progression of nonalcoholic fatty liver disease from steatosis to NASH. The purpose of this study was to examine whether CIH induces inflammatory changes in the liver in mice with diet-induced hepatic steatosis. C57BL/6J mice (n = 8) on a high-fat, high-cholesterol diet were exposed to CIH for 6 mo and were compared with mice on the same diet exposed to intermittent air (control; n = 8). CIH caused liver injury with an increase in serum ALT (461 +/- 58 U/l vs. 103 +/- 16 U/l in the control group; P < 0.01) and AST (637 +/- 37 U/l vs. 175 +/- 13 U/l in the control group; P < 0.001), whereas alkaline phosphatase and total bilirubin levels were unchanged. Histology revealed hepatic steatosis in both groups, with mild accentuation of fat staining in the zone 3 hepatocytes in mice exposed to CIH. Animals exposed to CIH exhibited lobular inflammation and fibrosis in the liver, which were not evident in control mice. CIH caused significant increases in lipid peroxidation in serum and liver tissue; significant increases in hepatic levels of myeloperoxidase and proinflammatory cytokines IL-1beta, IL-6, and CXC chemokine MIP-2; a trend toward an increase in TNF-alpha; and an increase in alpha1(I)-collagen mRNA. We conclude that CIH induces lipid peroxidation and inflammation in the livers of mice on a high-fat, high-cholesterol diet.
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PMID:Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. 1800 63

We investigated in vivo the effect of recombinant bactericidal/permeability-increasing protein (rBPI21) on high-mobility group box 1 protein (HMGB1) expression in sepsis and its potential mechanism. Using a sepsis model induced by cecal ligation and puncture (CLP), rats were randomly divided into four groups as follows: normal control group, sham-operated group, CLP group, and BPI treatment group. Animals were killed at designated time points, and blood and tissue samples from liver, lungs, kidneys, and small intestine were harvested to determine related variables. In addition, we observed the effect of treatment with rBPI21 on survival rate in septic rats. The results showed that endotoxin content and expression levels of HMGB1 and LPS binding protein/CD14 mRNA in various organs were significantly increased at 12 and 24 h after CLP, which can be attenuated by treatment with rBPI21 (P<0.05-0.01). Meanwhile, treatment with rBPI21 in septic rats can markedly reduce serum alanine aminotransferase, creatinine levels, and pulmonary myeloperoxidase activity at 12 and 24 h after CLP, increase diamine oxidase activity at both time points (P<0.05-0.01), and improve the 1- to 10-day survival rates in animals subjected to CLP (P=0.012). These findings suggest that treatment with rBPI21 can significantly reduce endotoxin contents and expression levels of HMGB1 and LPS binding protein/CD14 mRNA in various organs in sepsis induced by CLP, and can protect against multiple organ damage resulting from sepsis. The effect of rBPI21 inhibiting HMGB1 gene expression in sepsis might be associated with endotoxin-dependent mechanisms.
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PMID:Recombinant bactericidal/permeability-increasing protein inhibits endotoxin-induced high-mobility group box 1 protein gene expression in sepsis. 1769 35


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