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)

This study investigated the effect of a spontaneous nitric oxide (NO) donor, FK409 (FK), in a rat model of segmental hepatic ischemia. Rats were allocated to four experimental groups. Two of the groups underwent segmental hepatic ischemia of 60 min duration and received FK (0.4 mg/kg, iv) or vehicle alone before inducing ischemia and again 5 min before reperfusion. Sham-FK and sham groups were treated identically, but did not have vascular occlusion. Serum aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) were measured, and the livers were examined for histological evidence of injury, polymorphonuclear neutrophil (PMN) infiltration, and immunohistochemical expression of inducible NO synthase (iNOS) before and 6 h after reperfusion. AST, ALT, and LDH levels were significantly (p < .05) reduced 6 h after reperfusion in the FK-treated group compared with the vehicle-treated control group. FK treatment also reduced the degree of hepatic damage apparent on histopathology and reduced PMN infiltration and iNOS expression. Thus, FK treatment is protective against hepatic ischemia reperfusion injury and attenuates neutrophil infiltration and iNOS expression.
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PMID:NO donor ameliorates ischemia-reperfusion injury of the rat liver with iNOS attenuation. 1612 30

The potential use of hydrophilic cyclodextrins (CyDs) as an inhibitor for lipopolysaccharide (LPS) was examined. Of the five CyDs used in this study, dimethylacetyl-beta-cyclodextrin (DMA7-beta-CyD) had greater inhibitory activity than other CyDs against the production of nitric oxide (NO) and various proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) in murine macrophages stimulated with two serotypes of LPS and lipid A. The inhibitory effect of DMA7-beta-CyD on NO production was also observed in macrophages stimulated with lipoteichoic acid (LTA), but not peptidoglycan (PGN), polyinosinic-polycytidylic acid (poly I:C) or CpG oligonucleotide (CpG-ODN). Several studies have suggested that the inhibitory effects of DMA7-beta-CyD could be ascribed to the interaction with LPS. Simultaneous administration of DMA7-beta-CyD not only intraperitoneally but also intravenously and intraperitoneal injection of aqueous solution containing LPS and d-galactosamine in murine endotoxin shock model suppressed fatality. Also, DMA7-beta-CyD decreased blood level of TNF-alpha as well as serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) in mice. In conclusion, DMA7-beta-CyD may have promise as a new therapeutic agent for endotoxin shock induced by LPS.
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PMID:Inhibitory effects of dimethylacetyl-beta-cyclodextrin on lipopolysaccharide-induced macrophage activation and endotoxin shock in mice. 1621 16

Biliary atresia (BA) remains one of the most intractable liver diseases in children. The aim of this study was to investigate the possible roles of nitric oxide (NO) in BA. Serum levels of nitrite and nitrate (NO production) were determined using a colorimetric method from 65 post-operative BA patients and 12 healthy children. The patients were categorized into two groups according to their jaundice status, and serum alanine aminotransferase (ALT, a marker for liver injury). Unpaired t tests were used. Data are expressed as mean and SD in terms of mumol/l. Age and gender between BA patients and controls were comparable. Serum NO metabolites of BA patients was higher than the controls (79.77+/-21.22 vs. 65.75+/-9.44, P=0.001). Subgroup analysis revealed that there was no difference in serum nitrate/nitrite levels of BA patients without jaundice compared to those with jaundice (78.85+/-23.23 vs. 80.90+/-18.76, P=0.70). However, patients with serum ALT> or =100 IU/l had higher levels of serum NO metabolites compared to those with serum ALT<100 IU/l. In conclusion, NO production was elevated in BA patients compared to normal controls. Serum NO was associated with serum ALT levels, but not with jaundice status, in BA patients. These suggest that NO plays a role in the pathophysiology of liver injury in post-operative BA.
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PMID:Elevated serum nitric oxide metabolites in biliary atresia. 1628 36

From the leaves of Viburnum tinus L. (Adoxaceae) two acylated iridoid glucosides (viburtinoside A and B), a coumarin diglucoside scopoletin 7-O-beta-D-sophoroside and a natural occurred dinicotinic acid ester 2,6-di-C-methyl-nicotinic acid 3,5-diethyl ester were isolated. In addition to these, 10 known compounds were isolated, namely two bidesmosidic saponins, a hexamethoxy-flavone and five flavonol glycosides, as well as suspensolide A and oleanolic acid were isolated for the first time in this genus and species, respectively. The structures were determined mainly by spectroscopic methods (UV, IR, ESI-MS, 1H-, 13C NMR and DEPT). Toxicity of the investigated extract was determined (LD50=500 mg/kg). CCl4-induced hepatotoxicity has been evaluated in terms of the determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid peroxide and nitric oxide levels in serum and compared using adult male rats weighing 150-180 g. Their highly elevated levels were significantly reduced by treatment with the investigated aqueous methanol extract in dose-dependent manner.
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PMID:Phytochemical constituents and hepatoprotective activity of Viburnum tinus. 1630 55

Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study evaluated antioxidant and hepatoprotective activity of pomegranate flowers. Alcoholic (ethanolic) extract of flowers was prepared and used in the present study. The extract was found to contain a large amount of polyphenols and exhibit enormous reducing ability, both indicative of potent antioxidant ability. The extract showed 81.6% antioxidant activity in DPPH model system. The ability of extract to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) was tested and it was found to significantly scavenge superoxide (O(2)(.-)) (by up to 53.3%), hydrogen peroxide (H(2)O(2)) (by up to 30%), hydroxyl radicals (()OH) (by up to 37%) and nitric oxide (NO) (by up to 74.5%). The extract also inhibited (.)OH induced oxidation of lipids and proteins in vitro. These results indicated pomegranate flower extract to exert a significant antioxidant activity in vitro. The efficacy of extract was tested in vivo and it was found to exhibit a potent protective activity in acute oxidative tissue injury animal model: ferric nitrilotriacetate (Fe-NTA) induced hepatotoxicity in mice. Intraperitoneal administration of 9 mg/kg body wt. Fe-NTA to mice induced oxidative stress and liver injury. Pretreatment with pomegranate flower extract at a dose regimen of 50-150 mg/kg body wt. for a week significantly and dose dependently protected against Fe-NTA induced oxidative stress as well as hepatic injury. The extract afforded up to 60% protection against hepatic lipid peroxidation and preserved glutathione (GSH) levels and activities of antioxidant enzymes viz., catalase (CAT), glutathione peroxidase (GPX) glutathione reductase (GR) and glutathione-S-transferase (GST) by up to 36%, 28.5%, 28.7%, 40.2% and 42.5% respectively. A protection against Fe-NTA induced liver injury was apparent as inhibition in the modulation of liver markers viz., aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin and albumin in serum. The histopathological changes produced by Fe-NTA, such as ballooning degeneration, fatty changes, necrosis were also alleviated by the extract. These results indicate pomegranate flowers to possess potent antioxidant and hepatoprotective property, the former being probably responsible for the latter.
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PMID:Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. 1642 22

Human granulocytic anaplasmosis (HGA), caused by the granulocytic rickettsia-like organism Anaplasma phagocytophilum, is the 3rd most frequent vector-borne infection in North America. To understand the disease mechanisms of HGA, we developed a murine model that lacks clinical disease yet exhibits characteristic histopathologic and immunologic changes. Because the degree of hepatic histopathology is unrelated to high bacterial numbers, tissue injury in HGA is thought to occur due to products of innate immunity, such as nitric oxide (NO) and reactive nitrogen species (RNS) from cytokine-activated macrophages. To test the hypothesis that RNS cause hepatic tissue damage, mice received either water treated with a nonspecific inhibitor of inducible nitric oxide synthase, L-NAME, or untreated water for 7 to 10 d before infection and continuing thereafter. Mice were euthanized for tissue harvest at 0, 7, 14, or 21 d after infection to assess differences in histopathology, hepatic bacterial load, RNS quantity in urine and liver, and serum chemistry values. Overall, L-NAME treatment had a beneficial effect, resulting in lower histopathology scores and RNS levels compared with those of untreated mice. There were no significant differences in hepatic bacterial load among treatment groups of infected mice. The observed increases in serum glucose and alanine aminotransferase levels on day 14 appear to be unexpected side effects of L-NAME administration. HGA is best characterized as an immunopathologic disease rather than one caused by direct bacterial injury to the host. Therefore, human and animal patients with HGA likely would benefit from therapy targeting reduced inflammation to supplement anti-infective modalities.
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PMID:Role of reactive nitrogen species in development of hepatic injury in a C57bl/6 mouse model of human granulocytic anaplasmosis. 1652 60

Nitric oxide (NO) is known to be a messenger molecule that plays an important role in physiological and pathological conditions. It is synthesized by an enzyme called nitric oxide synthase (NOS). Inducible NOS (iNOS), one of the three isomers of NOS, has both protective and toxic properties. In this study, the role of NO has been evaluated by gastrointestinal symptoms induced by orlistat which is used in obesity treatment. Orlistat was given to Wistar rats with and without iNOS inhibition. The effects of orlistat and inhibition of NOS were studied. Glucose, urea, alanine transaminase (ALT), and gamma glutamil transpeptidase (GGT) were descreased after short- and long- term orlistat applications. Dexamethasone increased level of these enzymes. Cholesterol and triglyceride were increased in all experimental groups than the controls. This increment was more severe in animals received orlistat and dexamethasone together. Small intestinal tissue also were researched histologically and NADPH-diaphorase (NADPH-d) histochemistrically. Orlistat caused histological damages in brush border membranes, connective tissues of villi, and lymphocyte migration also increased. Dexamethasone treatment prevented these damages partially while orlistat increased the NOS distribution in the tissue sections. Dexamethasone, which is an iNOS inhibitor, decreased NADPH-d histochemistry. There was a similiar NOS distribution both in the control and orlistat+dexamethasone group. Hence, we concluded that long- term trials with orlistat and similar drugs are needed.
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PMID:Effects of orlistat and its relationship with nitric oxide in the small intestinal mucosa. 1654 24

Ovarian hormone depletion in ovariectomized experimental animals is a useful model with which to study the physiopathological consequences of menopause in women. It has been suggested that menopause is a risk factor for the induction of several cardiovascular disorders. In the present study we analyzed the effects of ovarian hormone depletion by ovariectomy (OVX) in a model of oxidative stress and cardiopathy induced by adriamycin (AD). To evaluate these effects, we measured parameters related to cardiac damage (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) and oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione, nitric oxide and carbonyl proteins) in cardiac tissue and erythrocytes. OVX was found to alter all markers of oxidative stress and cell damage in cardiac tissue. Similarly, the OVX-derived loss of ovarian hormones enhanced cardiac damage and oxidative stress induced by AD. Our results suggest that antioxidant status in cardiac tissue and erythrocytes is seriously compromised by OVX during the cardiomyopathy induced by AD in experimental animals. In conclusion, the absence of hormones caused by OVX or menopause may induce or accelerate pre-existing cardiovascular dysfunctions.
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PMID:Ovariectomy exacerbates oxidative stress and cardiopathy induced by adriamycin. 1660 31

The aim of this study was to investigate the contribution of inducible nitric oxide synthase (iNOS)-derived nitric oxide on the liver and lung injury following hepatic ischemia-reperfusion (I/R) using a novel and potent iNOS inhibitor, ONO-1714. Rats were subjected to 90 min of partial hepatic ischemia followed by 3, 6, 12, and 24 hr of reperfusion. Expression of iNOS mRNA peaked at 3 hr of reperfusion in the liver and lung. Plasma nitric oxide levels were increased fourfold at 24 hr of reperfusion and plasma ALT was increased, reaching a peak at 12 hr of reperfusion; both were significantly inhibited by ONO-1714. Histological examination revealed extensive liver damage, whereas this was not seen in the ONO-1714 group. Lung injury was not significantly changed in groups with versus without ONO-1714. Nitrotyrosine expression was seen in regions similar to those of the histological injuries of the liver, while this staining was absent in the ONO-1714 group. These data show that generation of peroxynitrite could be involved in the pathogenesis of liver injury but not lung injury after hepatic I/R. Inhibition of iNOS could be applied for attenuation of liver injury following hepatic I/R.
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PMID:Inhibition of inducible nitric oxide synthase prevents hepatic, but not pulmonary, injury following ischemia-reperfusion of rat liver. 1661 69

Chronic bile duct ligation (BDL) is a useful model of cirrhosis. However, its parallel plasma and liver changes in levels of cytokines and nitric oxide (NO), involved in liver damage, remain unknown. The aims of this work were to quantify both the plasma and hepatic levels of five cytokines and NO in cirrhotic rats, 28 days after bile BDL, and to analyze their relationship with liver damage markers. One group of male Wistar rats was bile duct ligated and another group was sham operated, both groups were sacrificed 28 days after BDL. Plasma and liver cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, -1beta, -10 (IL-6, -1beta, -10) and interferon-gamma (IFN-gamma), were measured by ELISA. Plasma and hepatic NO was determined as NO(2)(-)+NO(3)(-) by an enzymatic method. Alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase and bilirubins were determined in plasma. Collagen, lipid peroxidation and glycogen were quantified in liver. Two histopathological staining techniques were performed. BDL-induced cirrhosis was corroborated by the elevated liver damage markers and histopathological analysis. Chronic BDL significantly increased (P<0.05) most of plasma and hepatic cytokine levels and diminished the hepatic IFN-gamma amount. NO was increased in both tissues, but such change was only significant in plasma. Biliary cirrhosis produces interesting changes in plasma and hepatic levels of cytokines and NO. This finding in chronic BDL model in rats has not been previously described in both tissues for such cytokines and NO. Cytokines and NO imbalance favor establishment and perpetuation of cirrhosis.
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PMID:Chronic bile duct obstruction induces changes in plasma and hepatic levels of cytokines and nitric oxide in the rat. 1661 7


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