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

---

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

Naltrexone, an opioid antagonist, has been reported to possess an anti-inflammatory effect via blockade of opioid receptor. The aim of this study is to evaluate the protective effect of naltrexone on LPS-induced septic shock in rats. Sepsis was induced by administration of LPS (10 mg/kg, i.v.) in anesthetized rats. Results demonstrated that pretreatment with naltrexone (10 mg/kg, i.v.) significantly ameliorated hypotension and bradycardia of rats 6 h after LPS administration. In isolated blood vessel, study showed that pretreatment with naltrexone significantly improved norepinephrine-induced vasoconstriction and ACh-induced vasorelaxation in aorta of endotoxemic animals. Naltrexone significantly reduced the elevation of serum glutamate-oxalacetate transaminase and glutamate-pyruvate transaminase (as index of hepatic function) induced by LPS. The infiltration of polymorphonuclear neutrophils into liver 48 h after LPS treatment in mice was also reduced by naltrexone. On the other hand, naltrexone significantly decreased the levels of plasma TNF-alpha and inhibited overproduction of superoxide anions in aortic rings. However, naltrexone did not suppress the overproduction of NO (measured by its metabolites nitrite/nitrate in plasma) and iNOS expression in lungs induced by LPS. In in vitro study, naltrexone did not attenuate non-enzymatic iron-induced lipid peroxidation in rat brain homogenates. In conclusion, pretreatment with naltrexone significantly improved circulatory failure and hepatic dysfunction in sepsis. These effects were associated with reduction of TNF-alpha levels and superoxide anion formation, which may be attributed to antagonism of opioid receptors.
...
PMID:Effects of naltrexone on lipopolysaccharide-induced sepsis in rats. 1591 99

Ischemia/reperfusion injury (IRI) represents the major problem in clinical liver transplantation. We have shown that toll-like receptor 4 (TLR4) signaling is specifically required in initiating antigen-independent IRI leading to liver inflammation, whereas local induction of anti-oxidant heme oxygenase-1 (HO-1) is cytoprotective. This study analyzes in vivo interactions between HO-1 and sentinel TLR system in the pathophysiology of liver IRI. Using a 90-min lobar warm ischemia model, wild type (WT), TLR4 KO/mutant and TLR2 KO mice were first assessed for the severity of hepatocellular damage at 6 h postreperfusion. Unlike in WT or TLR2-deficient mice, disruption/absence of TLR4 pathway reduced IRI, as manifested by liver function (serum alanine aminotransferase levels), histology (Suzuki's scores), neutrophil infiltration (myeloperoxidase activity) and local/systemic TNF-alpha production (mRNA/protein levels). Moreover, defective TLR4 but not TLR2 signaling increased mRNA/protein HO-1 expression. In contrast, tin protoporphyrin-mediated HO-1 inhibition restored hepatic damage in otherwise IRI-resistant TLR4 mutant/KO mice. CoPP-induced HO-1 overexpression ameliorated hepatic damage in IRI-susceptible TLR2 KO mice, comparable with WT controls, and concomitantly diminished TLR4 levels. In conclusion, this study highlights the importance of cross talk between HO-1 and TLR system in the mechanism of hepatic IRI. Hepatic IRI represents a case for innate immunity in which HO-1 modulates proinflammatory responses that are triggered via TLR4 signaling, a putative HO-1 repressor.
...
PMID:Toll-like receptor and heme oxygenase-1 signaling in hepatic ischemia/reperfusion injury. 1599 25

To examine the role of histamine H1 and H2 receptors in the regulation of lipopolysaccharide (LPS)-induced liver injury, a combination of D-galactosamine and LPS (GalN/LPS) was administered to histamine H1 receptor knockout (H1-R KO) and H2 receptor knockout (H2-R KO) mice. The numbers of necrotic and apoptotic hepatocytes in the liver, as well as the levels of serum aspartate transaminase (AST) and alanine transaminase (ALT), were increased significantly by GalN/LPS treatment compared to the appropriate controls. Pretreatment with histamine ameliorated the GalN/LPS-induced necrotic and apoptotic changes in the hepatocytes and inhibited the elevation of serum AST and ALT levels. Histamine attenuated the GalN/LPS-induced increases in the levels of TNF-alpha, but augmented those of IL-10 both in the liver and serum. Histamine inhibited the GalN/LPS-induced caspase-3 activity in the liver. Furthermore, these effects of histamine were completely or partially attenuated in H2-R KO mice, but not in H1-R KO mice. Peritoneal macrophages from H2-R KO mice exhibited blunted changes in the effects of histamine on LPS-induced TNF-alpha and IL-10 production in vitro compared to the wild-type (WT) controls. In summary, the present findings suggest that the histamine H2-R-TNF-alpha and -IL-10 pathways play protective roles in endotoxin-induced hepatic injury.
...
PMID:The role of histamine H1 receptor and H2 receptor in LPS-induced liver injury. 1605 91

Moderate alcohol consumption is associated with increased insulin sensitivity and a reduced risk for type 2 diabetes. An important endogenous mediator of insulin sensitivity is adiponectin (AN), an adipokine that displays numerous antiatherogenic, antidiabetogenic and antiinflammatory effects. Recently, acute increase in alcohol consumption has been shown to be associated with increase in plasma adiponectin and, concomitantly, insulin sensitivity. Whether chronic alcohol consumption predicts an increase in plasma AN and whether this is independent of adiposity, markers of liver dysfunction, and plasma adipokines such as tumor necrosis factor (TNF)-alpha is not known. We, therefore, investigated these relationships in 75 men who were diagnosed with liver steatosis using ultrasound/liver biopsy. We examined 75 men, who were diagnosed for having liver steatosis (ultrasound/liver biopsy). Each filled in a questionnaire on alcohol intake. Subjects were divided into two subgroups according to alcohol history and CDT concentrations--drinkers and non-drinkers. All individuals were examined for serum concentrations of AN, glucose, triglycerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate transferase (GMT) activity; carbohydrate-deficient transferrin (CDT%) a marker of chronic alcohol consumption, insulin and TNF-alpha. The Quicki insulin sensitivity index was calculated. Forty-eight individuals were found to be moderate drinkers and 27 subjects non-drinkers. Moderate drinkers had significantly higher concentrations of AN (13.8 +/- 3,7 versus 9.1 +/- 5.4 mg/l, means +/- SD, p = 0.012) compared with non-drinkers, independent of adiposity. Plasma AN concentrations in the whole group were positively correlated with TNF-alpha concentrations (r = 0.6; p = 0.0001), CDT (r = 0.26; p = 0.0084), AST/ALT index (r = 0.3, p = 0.009), AST (r = 0.29; p = 0.011) and GMT (r = 0.29; p = 0.011) and negatively with BMI (r = -0.48; p = 0.0002) and glycemia (r = -0.22; p = 0.049). The positive associations of AN with TNF-alpha (0.8; p = 0.001), CDT (0.55; p = 0.017), AST/ALT index (0.55; p = 0.019) and the negative correlation with glycemia (-0.35; p = 0.0158) were independent of BMI. Stratified according to alcohol intake, in moderate drinkers, a positive correlation was found between AN and TNF-alpha concentrations (r = 0.6, p = 0.0001, AST/ALT index (r = 0.34, p = 0.0295) whereas in non-drinkers no such correlations were found. The concentration of AN and BMI displayed a negative correlation in both drinker and nondrinker patients (r = -0.42, p = 0.01 and -0.61; p = 0.012, respectively). We concluded that plasma AN is higher in moderate drinkers compared to non-drinkers, even after correction for BMI. Drinkers suffering from liver steatosis were found to have a positive correlation between AN concentrations, laboratory markers of liver disease and TNF-alpha. Such correlation was absent in non-drinkers suffering from liver steatosis. This suggests that alcohol may modulate the inhibitory effect of TNF-alpha on AN production, and thus, increase its plasma concentrations.
...
PMID:High adiponectin and TNF-alpha levels in moderate drinkers suffering from liver steatosis: comparison with non drinkers suffering from similar hepatopathy. 1617 Mar 95

In vivo protective effects of s-allyl cysteine (SAC) and s-propyl cysteine (SPC) against acetaminophen-induced hepatotoxicity in Balb/cA mice were studied. SAC and SPC at 1g/L were added into drinking water for four weeks and followed by acetaminophen treatment. Acetaminophen treatment significantly depleted glutathione content, increased oxidation stress and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities (P < 0.05); however, the intake of SAC or SPC significantly alleviated glutathione depletion and the elevation of ALT and AST, enhanced glutathione peroxidase activity, and lowered malondialdehyde formation (P < 0.05). Plasma levels of C-reactive protein (CRP), von Willebrand factor (vWF), IL-6, IL-10 and TNF-alpha were significantly increased by acetaminophen treatment (P < 0.05); and SAC or SPC intake significantly suppressed acetaminophen-induced elevation of CRP, vWF and the three cytokines (P < 0.05). Acetaminophen treatment also significantly increased plasminogen activator inhibitor-1 (PAI-1) activity and plasma fibrinogen level, and decreased antithrombin III (AT-III) and protein C activities (P < 0.05). SAC or SPC intake alleviated AT-III and protein C reduction (P < 0.05); but did not affect PAI-1 activity and plasma fibrinogen level (P > 0.05). These data suggest that SAC and SPC are potential multiple-protective agents against acetaminophen-induced hepatotoxicity.
...
PMID:Protective effect of s-allyl cysteine and s-propyl cysteine on acetaminophen-induced hepatotoxicity in mice. 1618 16

The aim of this work was to investigate the protective role of baker's yeast Saccharomyces cerevisiae against the hepatotoxic effect of the drug flutamide that is widely used for treatment of metastatic prostate adenocarcinoma. Administration of flutamide to adult male rats in a dose of 100 mg/kg b.w. daily for 15 days resulted in serious hepatic injury. Highly significant increase in each of serum ALT, ALP, bilirubin, bile acids and cholesterol level, relative to the control group, was observed. Also, a highly significant increase in the serum glutathione-S-transferase isoforms: alpha-GST and pi-GST and each of TNF-alpha and NO levels was recorded. Moreover, highly significant decrease in hepatic glutathione peroxidase and superoxide dismutase activities was observed. In addition, the authors noticed a significant increase in serum testosterone levels with concomitant highly significant increase in serum acid phosphatase activity. Prophylactic treatment of male rats with baker's yeast in a dose of 4.8 mg/kg b.w. daily for 15 days, followed by a combination of flutamide (100 mg/kg b.w.) and yeast (4.8 mg/kg b.w.) daily for other 15 days resulted in marked improvement in rat's liver function, whereas the serum testosterone and acid phosphatase levels retained values parallel to those recorded for the flutamide-treated rats. Histological examination of liver tissues showed that flutamide caused hydropic degeneration, necrotic areas and marked increase in Kupffer cells. The central vein is congested with blood and signs of apoptosis appeared in the hepatocytes in the form of fragmentation of the nuclei and blebbing of the cytoplasm. On the other hand, in the rats treated with both yeast and flutamide, the hepatic cords were more regularly arranged, signs of degeneration or apoptosis were less pronounced and some hepatocytes appeared binucleated. The authors postulate that each one of the powerful antioxidative components in S. cerevisiae effectively participated in attenuation of the oxidative stress caused by flutamide metabolites, and in promoting regeneration of new hepatocytes and meanwhile could restore liver function beyond normal status.
...
PMID:Saccharomyces cerevisiae intervention for relieving flutamide-induced hepatotoxicity in male rats. 1622 70

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.
...
PMID:Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression. 1625 24

Genipin is a metabolite derived from the herbal medicine Inchinko-to. Little is known about the mechanism of genipin action on acute liver injury through inflammatory cytokines. We examined the effects of genipin on production of TNF-alpha in vivo and in vitro. Mice were given GalN/LPS with or without genipin treatment. All mice not given genipin died within 12h. But in mice given genipin, 8 of 15 mice survived for 24h after GalN/LPS administration. Histologically, hepatic necrosis and inflammatory cells infiltration were significantly slight in mice given genipin. Serum AST and ALT activity were significantly lower in mice given genipin. Serum and liver homogenate TNF-alpha levels were significantly lower in mice given genipin. However, in IL-6 and IL-1beta, there were no significant differences in mice given and not given genipin. TNF-alpha, NF-kappaB activation and TNF-alpha mRNA expression in a cultured mouse macrophage-like cell line J774.1 were significantly suppressed by genipin administration. In conclusion, the present findings suggest that genipin, a metabolite derived form the herbal medicine Inchinko-to improved acute liver dysfunction by suppressive effect of TNF-alpha production.
...
PMID:Genipin prevents fulminant hepatic failure resulting in reduction of lethality through the suppression of TNF-alpha production. 1629 60

Toll-like receptors (TLR) recognize pathogen-derived molecules and induce downstream activation of inflammatory pathways. Fatty liver has been shown to result in increased sensitivity to lipopolysaccharide (LPS), a TLR4 ligand. In this study, we investigated the roles of TLR2 and TLR4 in liver damage and on cytokine induction in a methionine-choline deficient (MCD) diet-induced model of nonalcoholic steatohepatitis. We found that mice with nonalcoholic fatty liver had increased liver injury and inflammatory cytokine induction after challenge with a TLR4 but not with a TLR2 ligand. TLR2 deficient mice were not protected against the development of steatohepatitis after MCD diet feeding. On the contrary, TLR2 mice had significantly higher levels of serum ALT and greater TNF-alpha levels after LPS challenge suggesting increased liver injury. This was associated with reduced production of IL-6, a cytokine with hepatoprotective effects in fatty liver. Increased liver injury in the MCD diet-fed TLR2 mice was associated with reduced baseline and LPS-induced NF-kB and PPRE binding compared to MCS controls. These results demonstrate that TLR2 deficiency results in increased liver injury in association with nonalcoholic steatohepatitis and may suggest a protective role for TLR2-mediated signals in liver injury.
...
PMID:Modulation of non-alcoholic steatohepatitis by pattern recognition receptors in mice: the role of toll-like receptors 2 and 4. 1634 99

P-selectin glycoprotein ligand-1 (PSGL-1) mediates the initial tethering of leukocytes to activated platelets and endothelium. We report molecular cloning and characterization of the rat PSGL-1 gene. A neutralizing Ab was generated, and its binding epitope was mapped to the N-terminal binding region of rat PSGL-1. We examined the effects of early PSGL-1 blockade in rat liver models of cold ischemia, followed by ex vivo reperfusion or transplantation (orthotopic liver transplantation (OLT)) using an anti-PSGL-1 Ab with diminished Fc-mediated effector function. In the ex vivo hepatic cold ischemia and reperfusion model, pretreatment with anti-PSGL-1 Ab improved portal venous flow, increased bile production, and decreased hepatocellular damage. Rat pretreatment with anti-PSGL-1 Ab prevented hepatic insult in a model of cold ischemia, followed by OLT, as assessed by 1) decreased hepatocellular damage (serum glutamic oxaloacetic transaminase/glutamic-pyruvic transaminase levels), and ameliorated histological features of ischemia/reperfusion injury, consistent with extended OLT survival; 2) reduced intrahepatic leukocyte infiltration, as evidenced by decreased expression of P-selectin, ED-1, CD3, and OX-62 cells; 3) inhibited expression of proinflammatory cytokine genes (TNF-alpha, IL-1beta, IL-6, IFN-gamma, and IL-2); and 4) prevented hepatic apoptosis accompanied by up-regulation of antiapoptotic Bcl-2/Bcl-xL protective genes. Thus, targeting PSGL-1 with a blocking Ab that has diminished Fc-mediated effector function is a simple and effective strategy that provides the rationale for novel therapeutic approaches to maximize the organ donor pool through the safer use of liver transplants despite prolonged periods of cold ischemia.
...
PMID:Molecular characterization of rat leukocyte P-selectin glycoprotein ligand-1 and effect of its blockade: protection from ischemia-reperfusion injury in liver transplantation. 1636 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---