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)

Punica granatum L. (pomegranate) is a widely used plant that has high nutritional value. The aim of this study was to assess the effect of chronic administration of pomegranate peel extract (PPE) on liver fibrosis induced by bile duct ligation (BDL) in rats. PPE (50 mg kg(-1)) or saline was administered orally for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage. Proinflammatory cytokines (tumor necrosis factor-alpha and interleukin 1 beta) in the serum and antioxidant capacity (AOC) were measured in plasma samples. Samples of liver tissue were taken for measurement of hepatic malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence assay. Serum AST, ALT, LDH and cytokines were elevated in the BDL group compared with the control group; this increase was significantly decreased by PPE treatment. Plasma AOC and hepatic GSH levels were significantly depressed by BDL but were increased back to control levels in the PPE-treated BDL group. Increases in tissue MDA levels and MPO activity due to BDL were reduced back to control levels by PPE treatment. Similarly, increased hepatic collagen content in the BDL rats was reduced to the level of the control group with PPE treatment. Thus, chronic PPE administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic structure and function. It therefore seems likely that PPE, with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver from fibrosis and oxidative injury due to biliary obstruction.
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PMID:Pomegranate peel extract prevents liver fibrosis in biliary-obstructed rats. 1793 10

The aim of this study was to evaluate and compare the effectiveness of N-acetylcysteine (NAC) and liposomally-encapsulated NAC (L-NAC) in ameliorating the hepatotoxic effects of lipopolysaccharide (LPS). LPS, a major cell wall molecule of Gram-negative bacteria and the principal initiator of septic shock, causes liver injury in vivo that is dependent on neutrophils, platelets, and several inflammatory mediators, including tumour necrosis factor-alpha (TNF-alpha). Male Sprague-Dawley rats were pretreated intravenously with saline, plain liposomes (dipalmitoylphosphatidylcholine [DPPC]), NAC (25 mg/kg body weight), or L-NAC (25 mg/kg NAC body weight) and 4 h later were challenged intravenously with LPS (Escherichia coli O111:B4, 1.0 mg/kg body weight); animals were killed 20 h post-LPS challenge. Hepatic cell injury was evaluated by measuring the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in plasma. LPS-induced activation of the inflammatory response was evaluated by measuring the levels of myeloperoxidase activity and chloramine concentration in liver homogenates as well as TNF-alpha levels in plasma. The hepatic levels of lipid peroxidation products and non-protein thiols (NPSH) were used to assess the extent of involvement of oxidative stress mechanisms. In general, challenge of animals with LPS resulted in hepatic injuries, activation of the inflammatory response, decreases in NPSH levels and increases in the levels of lipid peroxidation products (malondialdehyde and 4-hydroxyalkenals). Pretreatment of animals with NAC or empty liposomes did not have any significant protective effect against LPS-induced hepatotoxicity. On the other hand, pretreatment of animals with an equivalent dose of L-NAC conferred protection against the liver injuries induced following LPS challenge. These data suggest that NAC when delivered as a liposomal formulation is a potentially more effective prophylactic pharmacological agent in alleviating LPS-induced liver injuries.
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PMID:Prophylactic effect of liposomal N-acetylcysteine against LPS-induced liver injuries. 1798 88

Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats were injected intravenously with lipopolysaccharide (LPS) 24 h after 70% hepatectomy. Glycyrrhizin, pre-administered three times with 24 h intervals 48 h before hepatectomy, prolonged the survival of rats submitted to partial hepatectomy and LPS injection, compared with saline controls. Glycyrrhizin was shown to attenuate histological hepatic changes and significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase, at all the indicated times (6 rats from each were sacrificed 1, 3, 6, and 9 h after LPS injection), compared with saline controls. Glycyrrhizin also significantly inhibited hepatocyte apoptosis by down-regulating the expression of caspase-3 and inhibiting the release of cytochrome C from mitochondria into the cytoplasm. The anti-inflammatory activity of glycyrrhizin may rely on the inhibition of release of tumor necrosis factor-a, myeloperoxidase activity, and translocation of nuclear factor-kappa B into the nuclei. Glycyrrhizin also up-regulated the expression of proliferating cell nuclear antigen, implying that it might be able to promote regeneration of livers harmed by LPS. In summary, glycyrrhizin may represent a potent drug protecting the liver against endotoxin-induced injury, especially after massive hepatectomy.
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PMID:Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats. 1799 67

Endotoxemia is a life-threatening, inflammatory condition that involves multiple organ injury and dysfunction. Preprotachykinin-A (PPT-A) gene products, substance P (SP), and neurokinin-A have been shown to play an important role in neurogenic inflammation. To investigate the role of PPT-A gene products on multiple organ injury in LPS-induced endotoxemia, endotoxemia was induced by LPS administration (10 mg/kg, i.p.) in PPT-A gene-deficient mice (PPTA(-/-)) and the wild-type (WT) control mice (PPT-A+/+). I.p. administration of LPS to WT mice caused a significant increase in circulating levels of SP as well as in liver, lung, and kidney. PPT-A gene deletion significantly protected against liver, pulmonary, and renal injury following LPS-induced endotoxemia, as evidenced by tissue myeloperoxidase activities, plasma alanine aminotransferase, aspartate aminotransferase levels, and histological examination. Furthermore, PPT-A(-/-) mice had significantly attenuated chemokines, proinflammatory cytokines, and adhesion molecule levels in the liver, lung, and kidney. These results show that PPT-A gene products are critical proinflammatory mediators in endotoxemia and the associated multiple organ injury. In addition, the data suggest that deletion of the PPT-A gene protected mice against organ damage in endotoxemia by disruption in neutrophil recruitment.
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PMID:Role of preprotachykinin-A gene products on multiple organ injury in LPS-induced endotoxemia. 1799 2

This study was designed to determine the possible protective effect of grape seed extract (GSE), a widely used antioxidant dietary supplement, on hepatic ischemia/reperfusion (I/R) injury. Wistar albino rats were subjected to 45 min of hepatic ischemia, followed by a 60 min reperfusion period. GSE was administered in a dose of 50 mg/kg/day orally for 15 days before I/R injury and repeated before the reperfusion period. Liver samples were taken for histological examination or determination of hepatic malondialdehyde (MDA), glutathione (GSH) and myeloperoxidase (MPO) activity. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver functions. Lactate dehydrogenase (LDH) and cytokines (TNF-alpha and IL-1 beta) were also assayed in serum samples for the evaluation of generalized tissue damage. Ischemia/reperfusion caused a significant decrease in hepatic GSH, and significant increases in MDA level, and MPO activity. Serum AST and ALT levels, as well as LDH activity and plasma TNF-alpha and IL-1beta levels were also elevated in the I/R group. Treatment with GSE reversed all these biochemical parameters as well as histological alterations induced by I/R. In conclusion, GSE reduced I/R-induced organ injury through its ability to balance the oxidant-antioxidant status, to inhibit neutrophil infiltration and to regulate the release of inflammatory mediators.
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PMID:Grape seed extract treatment reduces hepatic ischemia-reperfusion injury in rats. 1816 41

Endosulfan is a chlorinated cyclodiene insecticide which induces oxidative stress. In this study, we investigated the possible protective effect of melatonin, an antioxidant agent, against endosulfan (Endo)-induced toxicity in rats. Wistar albino rats (n = 8) were administered endosulfan (22 mg/kg/day orally) followed by either saline (Endo group) or melatonin (10 mg/kg/day, Endo + Mel group) for 5 days. In other rats, saline (control group) or melatonin (10 mg/kg/day, Mel group) was injected for 5 days, following corn oil administration (vehicle of endosulfan). Measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were performed in liver and kidney. Furthermore, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine levels, lactate dehydrogenase (LDH) activity were measured in the serum samples, while tumor necrosis factor-alpha (TNF-alpha), interleukin-beta (IL-beta) and total antioxidant capacity (AOC) were assayed in plasma samples. Endosulfan administration caused a significant decrease in tissue GSH and plasma AOC, which was accompanied with significant rises in tissue MDA and collagen levels and MPO activity. Moreover, the proinflammatory mediators (TNF-alpha and IL-beta), LDH activity, AST, ALT, creatinine and BUN levels were significantly elevated in the endosulfan-treated rats. On the other hand, melatonin treatment reversed all these biochemical alterations induced by endosulfan. Our results suggest that oxidative mechanisms play an important role in endosulfan-induced tissue damage and melatonin, by inhibiting neutrophil infiltration, balancing oxidant-antioxidant status and regulating the generation of inflammatory mediators, ameliorates oxidative organ injury as a result of endosulfan toxicity.
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PMID:Melatonin protects against endosulfan-induced oxidative tissue damage in rats. 1820 31

Resveratrol administration after adverse circulatory conditions is known to be protective, however, the mechanism by which resveratrol produces the salutary effects remains unknown. Recently, it was shown that resveratrol activates estrogen receptor (ER) in endothelial cells. We hypothesized that resveratrol administration in males after trauma-hemorrhage decreases cytokine production and protects against hepatic injury through an ER-dependent pathway. To study this, male Sprague-Dawley rats were subjected to trauma-hemorrhage (mean blood pressure, 40 mmHg for 90 min) then resuscitation. A single dose of resveratrol (30 mg/kg of body weight) with or without an ER antagonist (ICI 182,780), ICI 182,780, or vehicle was administered i.v. during resuscitation. Tissue myeloperoxidase activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant 1 (CINC-1), CINC-3, intercellular adhesion molecule 1, and interleukin 6 (IL-6) levels in the liver and plasma aspartate aminotransferase and alanine aminotransferase concentrations were measured at 2 and 24 h postresuscitation (n = 6 rats per group). One-way ANOVA and Tukey test were used for statistical analysis. Results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, CINC-1, CINC-3, intercellular adhesion molecule 1, and IL-6 levels and plasma aspartate aminotransferase and alanine aminotransferase concentrations. These parameters were significantly improved in the resveratrol-treated rats at both 2 and 24 h postresuscitation. Coadministration of the ER antagonist ICI 182,780 prevented the beneficial effects of resveratrol administration on postresuscitation proinflammatory responses and hepatic injury. Thus, resveratrol administration after trauma-hemorrhage attenuated hepatic injury, likely through reduction of proinflammatory mediators. Resveratrol-mediated hepatic preservation seemed to progress via an ER-related pathway.
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PMID:Resveratrol attenuates hepatic injury after trauma-hemorrhage via estrogen receptor-related pathway. 1827 52

Severe acute pancreatitis (SAP) characterized by atrocious progression and numerous complications often leads to a high mortality rate due to hypermetabolism, systemic inflammatory response syndrome (SIRS), and multiple organs dysfunction syndrome (MODS). Studies have revealed that both early enteral nutrition (EEN) and emodin are potent agents in the management of SAP. However, whether the combined strategy is rational and more effective than either one alone remains unknown. In this regard, Wistar rats were treated with emodin-assisted EEN (EAEEN) through enteral nutrient tubes after induction of SAP by retrograde infusion of 5.0% sodium taurocholate into the common pancreatic duct. Serum levels of amylase, tumor necrosis factor-alpha (TNF-alpha), angiotensin II (AngII), maleic dialdehyde (MDA), glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) and C-reactive protein (CRP), intestinal secretory IgA (SIgA), pancreatic and hepatic myeloperoxidase (MPO) activity as well as plasma levels of D-lactate and endotoxin were measured. In addition, pathologic alterations of pancreas and liver were observed microscopically. We found that EAEEN could significantly ameliorate these parameters and prevent pancreas and liver from serious damage. In conclusion, Our results indicated that EAEEN could exert beneficial effects on experimental SAP and obviously abate the severity of secondary hepatic injury. The combined strategy was safe and more effective than either one alone in the acute stage of SAP. This study also provided an experimental base for the clinical treatment of SAP patients with EAEEN.
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PMID:The effect of emodin-assisted early enteral nutrition on severe acute pancreatitis and secondary hepatic injury. 1828 70

Although IPC (ischaemic preconditioning) is considered as a protective strategy in HI/R (hepatic ischaemia/reperfusion), the mechanisms for this effect have not been fully elucidated. In the present study we investigate whether PPC (pharmacological preconditioning) by transient activation of A(1)R (adenosine A(1) receptor) protects against long-term HI/R and whether the protective effects of IPC depend on A(1)R activation and whether both preconditionings affect remote organs. Wistar rats underwent IPC and long-term HI/R. Another set of animals were pharmacologically preconditioned with the A(1)R-agonist CCPA [2-chloro-N(6)-cyclopentyladenosine; 0.1 mg/kg of body weight, i.p. (intraperitoneally)] 24 h before HI/R. In other groups, rats received an A(1)R-antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine; 0.1 mg/kg of body weight, i.p.) 24 h before HI/R. Hepatic damage was evaluated by transaminase [AST (aspartate transaminase), ALT (alanine transaminase)] release; inflammation was assessed by hepatic MPO (myeloperoxidase) and serum TNFalpha (tumour necrosis factor alpha) and NO; oxidative stress was estimated by MDA (malondialdehyde) and 4-HDA (4-hydroxyalkenals), SOD (superoxide dismutase) activity, GSH and ADA (adenosine deaminase) as adenosine metabolism. Both preconditionings protected liver and lung against HI/R as indicated by the reduction in transaminases, MPO, MDA+4-HDA, NO, TNFalpha and ADA activity as compared with HI/R (P<0.05). However, pre-treatment with DPCPX abolished the protective effects of IPC and PPC. Preconditionings induced a significant increase in hepatic MnSOD (manganese SOD) activity and NO generation compared with the sham group, and this activity was abolished by DPCPX pre-treatment. A(1)R activation induced hepatic delayed preconditioning and blockade of A(1)R abolished hepatic IPC. IPC, as well as PPC, were able to prevent lung damage. These protective effects are associated with a reduction in oxidative stress, inflammation and endogenous antioxidant preservation.
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PMID:Ischaemic and pharmacological preconditionings protect liver via adenosine and redox status following hepatic ischaemia/reperfusion in rats. 1830 14

Extracellular adenosine has been implicated as an innate antiinflammatory metabolite, particularly during conditions of limited oxygen availability such as ischemia. Because extracellular adenosine generation is primarily produced via phosphohydrolysis from its precursor molecule adenosine-monophosphate (AMP) through the enzyme ecto-5'-nucleotidase (CD73), we examined the contribution of CD73-dependent adenosine production in modulation of intestinal ischemia-reperfusion (IR) injury. Following transcriptional and translational profiling of intestinal tissue that revealed a prominent induction of murine CD73, we next determined the role of CD73 in protection against intestinal IR injury. Interestingly, pharmacological inhibition or targeted gene deletion of CD73 significantly enhanced not only local intestinal injury, but also secondary organ injury, following IR as measured by intestinal and lung myeloperoxidase, aspartate and alanine aminotransferase, interleukin (IL) -1, IL-6, and histological injury. To confirm the role of CD73 in intestinal adenosine production, we measured adenosine tissue levels and found that they were increased with IR injury. In contrast, CD73-deficient (cd73(-/-)) mice had lower adenosine levels at baseline and no increase with IR injury. Finally, reconstitution of cd73(-/-) mice or treatment of wild-type mice with soluble 5'-nucleotidase was associated with significantly lower levels of injury. These data reveal a previously unrecognized role of CD73 in attenuating intestinal IR-mediated injury.
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PMID:Role of extracellular nucleotide phosphohydrolysis in intestinal ischemia-reperfusion injury. 1835 66


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