Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that fructose-1,6-diphosphate (FDP) stimulates the synthesis of nitric oxide probably by stimulating the hepatic inducible nitric oxide synthase (iNOS). The aim of the present study was to evaluate the hepatoprotective role of FDP in acetaminophen-induced liver injury and whether this hepatoprotective effect is mediated by nitric oxide. Liver injury was induced in adult Sprague-Dawley rats by the administration of acetaminophen (1.6 g/kg by gavage) 10 min prior to the intraperitoneal injection of either FDP or normal saline. Liver injury was assessed by alanine aminotransferase (ALT) activity in the serum. iNOS and malondialdehyde (MDA) levels were determined in liver homogenates. Acetaminophen produced striking elevations of serum ALT, high MDA levels and a profound decrease in the liver iNOS. Administration of FDP attenuated the ALT and MDA elevations and prevented the liver iNOS depletion caused by acetaminophen. Pretreatment of the animals with the iNOS inhibitor L-NAME abolished this hepatoprotection. These findings suggest that FDP protects against acetaminophen-induced liver injury, at least partly, by stimulating production of nitric oxide.
 ...
PMID:Fructose diphosphate attenuates the acetaminophen-induced liver injury in the rat evidence for involvement of nitric oxide. 1568 24

We assessed the prevention of hepatic fibrogenesis by water-extract of Panax notoginseng Buck F.H. Chen. (Arialiaceae) root (PNS) in Long-Evans rats with cinnamon coat color (LEC rats). LEC rats were divided into three groups A, fed on a basal diet (BD); B, fed on BD plus 1% PNS; and C), fed on BD plus 0.005% lycopene as a control. All rats were sacrificed at 26 weeks of age. The percentage of the total area involved by fibrosis was 1.46 +/- 0.47 in group A, 0.83 +/- 0.10 in B (P=0.0030, B vs A) and 0.91 +/- 0.45 in C (P=0.0035, C vs. A). The percentage of the total area that was stained for alpha-SMA was 0.56 +/- 0.34 in group A, 0.15 +/- 0.02 in B (P=0.0016, B vs. A and 0.11 +/- 0.01 in C (P=0.0025, C vs. A. In group B, malondialdehyde (MDA) in the liver was lower than in group C (P=0.007). In group C, the concentration of iron in the liver was lower than in group A (P=0.0053). Thus, PNS suppressed fibrogenesis through reduced generation of lipid peroxides. The mechanisms of this preventive effect of fibrogenesis with PNS were suggested to inhibit the stellate cell activity. Second objective of this study was to determine whether PNS affects hepatic microvascular dysfunction elicited by gut ischemia and reperfusion (I/R), since gut I/R causes hepatic microvascular dysfunction, and to investigate the role of nitric oxide (NO). Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor the number of non-perfused sinusoids (NPS). In another set of experiments, PNS (1 g/kg per day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. In control rats, gut I/R elicited increases in the number of NPS, and plasma TNF-alpha and ALT activities, and these changes were mitigated by the pretreatment with PNS. Pretreatment with an NO synthase inhibitor diminished the protective effects of PNS on the increase in NPS and plasma TNF-alpha levels, but not its effect on the increase in plasma ALT activities. Pretreatment with PNS increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. These results suggest that PNS attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-alpha production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect.
 ...
PMID:A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats. 1569 47

In this study, we investigated the interaction between lipopolysaccharide (LPS) and lead (Pb) and the involvement of tumor necrosis factor-alpha (TNF-alpha) and oxidative stress in Pb-plus-LPS (Pb/LPS)-induced liver damage in rats. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-alpha, nitric oxide (NO), and lipid peroxidation (LPO) were determined in rats treated with Pb and/or LPS. Pb ranging from 0 to 15 mg/kg dose dependently increased AST, ALT, NO, or LPO in LPS-treated rats. Pretreatment with iNOS inhibitor 1400W reduced NO, LPO, TNF-alpha, AST, and ALT in Pb/LPS-treated rats. Thus, Pb increased LPS-induced liver damage, which might be associated with increased NO-initiated oxidative stress and TNF-alpha in rats.
 ...
PMID:Coexposure of lead- and lipopolysaccharide-induced liver injury in rats: involvement of nitric oxide-initiated oxidative stress and TNF-alpha. 1580 60

Mercury is a widespread metal in the environment and consequently large populations are currently exposed to low levels of mercury. Endotoxin, a component of the Gram-negative bacteria, promotes inflammatory responses. We recently reported that mercury modulates the production of nitric oxide and various inflammatory cytokines induced by endotoxin in a macrophage cell line (Nitric Oxide 2002, 7:67). The present study was designed to determine the impact of mercury on endotoxin-induced inflammatory cytokine expression and corresponding signal transduction in mouse liver. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercury in drinking water for 14 days and at the end of the treatment period lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 hr prior to euthanasia. The doses of mercury and LPS did not cause hepatotoxicity as indicated by unaltered circulating alanine aminotransferase and aspartate aminotransferase levels. Mercury decreased liver glutathione (GSH) and with LPS additively decreased GSH. Mercury activated p38 mitogen-activated protein kinase (MAPK) and additively increased LPS-induced p38 MAPK phosphorylation. In contrast, mercury alone had no effect on activation of extracellular signal-regulated kinase (ERK) but inhibited LPS-induced ERK activation. Mercury increased the expression of tumor necrosis factor alpha (TNFalpha) and further potentiated LPS-induced TNFalpha expression. Mercury did not affect LPS-induced interleukin (IL)-1beta expression but decreased LPS-induced IL-6 expression. Results indicated that low levels of mercury augment LPS-induced TNFalpha expression by altering GSH and p38 MAPK. Mercury modulates LPS-induced p38 and ERK activation and downstream TNFalpha and IL-6 expression in mouse liver.
 ...
PMID:Mercury alters endotoxin-induced inflammatory cytokine expression in liver: differential roles of p38 and extracellular signal-regulated mitogen-activated protein kinases. 1580 65

We examined the role of nitric oxide (NO) produced by an inducible isoform of NO synthase (iNOS) using N[6]-(iminoethyl)-lysine (L-NIL), a selective iNOS inhibitor, in the rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) and investigated changes in organ function, plasma levels of NOX (metabolites of NO) and endothelin. We induced experimental DIC by the sustained infusion of 30 mg kg(-1) LPS for 4 h via the tail vein. We then investigated the effect of L-NIL (6 mg kg(-1), from - 0.5 to 4 h) on LPS-induced DIC. Blood was withdrawn at 4 and 8 h, and all four groups (LPS with or without L-NIL at 4 and 8 h) consisted of eight rats. Three of the animals in the 8-h LPS group died, and we examined blood samples from five rats in this group. None of the other rats died. The LPS-induced elevation of creatinine, alanine aminotransferase, glomerular fibrin deposition and plasminogen activator inhibitor was significantly suppressed by L-NIL coadministration, although L-NIL did not affect the platelet count, fibrinogen concentration or the level of thrombin-antithrombin complex. Moreover, plasma levels of the D-dimer that reflect the lysis of cross-linked fibrin were significantly increased by L-NIL coadministration in the LPS-induced DIC model. Plasma levels of NOX and endothelin were obviously increased by LPS infusion. However, both levels were significantly suppressed in the LPS + L-NIL group, when compared with the LPS group. Although mean arterial pressure (MAP) was significantly decreased between 2 and 8 h compared with the control in the LPS group, this depression was significantly attenuated in the LPS + L-NIL group. Our results suggest that NO induced by iNOS contributes to hypotension (depressed MAP), the progression of hepatic and renal dysfunction, microthrombus deposition and elevated endothelin levels in the rat model of LPS-induced DIC.
 ...
PMID:Selective inducible nitric oxide synthase inhibition attenuates organ dysfunction and elevated endothelin levels in LPS-induced DIC model rats. 1586 3

Nutritional supplementation with glutamine, arginine and their precursors has been proposed to contribute to the protection against ischemia-reperfusion-related injuries. The aim of this study was to evaluate in an isolated perfused rat liver model the preventive effect of a 4-day oral ornithine alpha-ketoglutarate (OKG) supplementation against warm ischemia-reperfusion (I-R) injury, and the involvement of nitric oxide synthesis. Rats were fed a controlled regimen supplemented with either OKG (5 g kg(-1); n=15) or an isonitrogenous mixture of non-essential amino acids (Control; n=6) for 4 days. Livers were subsequently prepared for isolated perfusion experiments, including a 45 min no-flow ischemic period. The OKG-treated group was divided into two groups according to the absence (OKG; n=8) or presence of a NO-synthase inhibitor, L-N(omega)-nitro-arginine methyl ester (OKG L-NAME; n=7) during liver perfusion. Liver cytolysis after ischemia was demonstrated by an elevated alanine aminotransferase release during the last 15 min of reperfusion that was significantly higher in the OKG-L-NAME group. Tumor necrosis factor alpha (TNF(alpha)) production was transiently increased only in the control group just after ischemia. At the end of the reperfusion period, liver superoxide dismutase activity was significantly lower in the OKG-L-NAME group compared to control animals. Dietary OKG administration had only a limited effect in this model of mild hepatic I-R, leading mainly to reduced TNF(alpha) production. As the content of lipid peroxidation products was not modified, it seems that OKG acts on the inflammatory response rather than on oxidative reactions. This action can tentatively be attributed to the role of OKG as a glutamine precursor rather than to the synthesis of arginine and nitric oxide.
 ...
PMID:Does dietary ornithine alpha-ketoglutarate supplementation protect the liver against ischemia-reperfusion injury? 1589 23

O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO) is a liver-selective nitric oxide donor that has been shown to protect against hepatotoxic effects of endotoxin, acetaminophen and cadmium. This study examined the effects of V-PYRRO/NO on alpha-naphthylisothiocyanate (ANIT)-induced hepatotoxicity in mice. Mice were given V-PYRRO/NO via osmotic pumps (5.4mg/ml; 0.5 microl/h) starting 24h before receiving a hepatotoxic dose of ANIT (150mg/kg in olive oil, i.g.), and continuing for additional 48h (3-day pumps). V-PYRRO/NO administration partially ameliorated ANIT-induced hepatotoxicity, as evidenced by reduced serum alanine aminotransferase and alkaline phosphatase, markers of liver cell death, and by improved liver pathology. However, V-PYRRO/NO had no effect on ANIT-induced cholestasis, as ANIT-increased serum bilirubin levels and gamma-glutamyl transpeptidase activity were not ameliorated. Microarray and real time RT-PCR analysis revealed that ANIT intoxication altered expression of various genes, including genes encoding metabolic enzymes, transporter proteins, acute phase proteins, inflammation- and, apoptosis-related genes, as well as other genes related to liver injury. V-PYRRO/NO treatment attenuated ANIT-induced elevations in certain inflammation- and apoptosis-related genes, but had no effect on ANIT-induced disturbance on the expression of genes related to metabolism, transport, and acute phase proteins. Thus, the liver-selective NO donor, V-PYRRO/NO, was partially protective against ANIT-induced liver injury, without affecting ANIT-induced cholestasis and cholestasis-related gene expression.
 ...
PMID:Limited protective role of V-PYRRO/NO against cholestasis produced by alpha-naphthylisothiocyanate in mice. 1591 67

Boswellia serrata, Linn F (Burseraceae) is commonly used in Indian system of medicine (Ayurvedic) as an anti-inflammatory, analgesic, anti-arthritic and anti-proliferative agent. This study was planned to investigate the water-soluble fraction of the oleoresin gum of Boswellia serrata (BS extract) on lipopolysaccharide (LPS) induced nitric oxide (NO) production by macrophages under in vivo and in vitro conditions. In the previous condition, rats were fed on atherogenic diet (2.5% cholesterol, 1% cholic acid, 15.7 % saturated fat) along with the BS extract for 90 days. Blood was collected for lipid profile and toxicological safety parameters. Peritoneal macrophages were isolated and cultured to see the LPS induced NO production. Under in vivo experiment, BS extract significantly reduced serum total cholesterol (38-48 %), increased serum high-density lipoprotein- cholesterol (HDL-cholesterol, 22-30%). Under in vitro experiments with thioglycolate activated macrophages, it inhibited LPS induced (NO) production with IC 50 value at 662 ng /ml. Further, this fraction, in the dose of 15 mg/100 g body wt for 90 days, did not show any increase in serum glutamate-pyruvate transaminase (SGPT) and blood urea, in normal control animals. However, it significantly reversed the raised SGPT and blood urea in the atherogenic diet-fed animals. Transverse section of liver and kidney also supported its protective effect. Thus it may be concluded that water extract of Boswellia serrata possesses strong hypocholesterolemic property along with increase in serum HDL. It inhibits the LPS induced NO production by the activated rat peritoneal macrophages and show hepato-protective and reno-protective property.
 ...
PMID:Extract of gum resins of Boswellia serrata L. inhibits lipopolysaccharide induced nitric oxide production in rat macrophages along with hypolipidemic property. 1599 75

The present work is aimed at evaluating the protective effect of ferulic acid (FA), a naturally occurring phenolic compound on CCl4 induced toxicity. The activities of liver markers (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase), lipid peroxidative index (thiobarbituric acid-reactive substances, hydroperoxides, nitric oxide, protein carbonyl content), the antioxidant status (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione) were used as biomarkers to monitor the protective role of FA. The liver marker enzymes in plasma and lipid peroxidative index in liver and kidney were increased in CCl4-treated groups, which were decreased significantly on treatment with FA. The antioxidants, which were depleted in CCl4-treated groups, were improved significantly by FA treatment. Administration of FA to normal rats did not produce any harmful effects. Thus our results show that FA is an effective antioxidant without any side-effects and may be a great gain in the current search for natural therapy.
 ...
PMID:Ferulic acid, a natural protector against carbon tetrachloride-induced toxicity. 1601 37

Lead (Pb) increases lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), lipid peroxidation (LPO), and liver damage. In this study, we investigated the role of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase (MAPK) and the causal relationships between TNF-alpha, NO, and LPO in Pb-increased LPS-induced liver damage in rats. Treatment with PKC and p42/44 MAPK inhibitors significantly reduced Pb + LPS-induced NO, TNF-alpha, LPO, and liver damage, which was revealed by elevated serum levels of aspartate aminotransferase and alanine aminotransferase. Pb + LPS coexposure significantly increased phosphorylation of p42/44 MAPK and TNF-alpha expression in peripheral blood cells; however, exposure to Pb + LPS did not induce TNF-alpha, NO, or LPO production and p42/44 MAPK activation in the liver. Pentoxifylline, a TNF-alpha inhibitor, also reduced liver damage but did not alter NO or LPO in Pb + LPS-treated rats. Thus, Pb increased LPS-induced liver damage through PKC and p42/44 MAPK modulation of TNF-alpha and oxidative stress, but modulation of TNF-alpha did not affect NO or LPO in rats.
 ...
PMID:Modulation of tumor necrosis factor-alpha and oxidative stress through protein kinase C and P42/44 mitogen-activated protein kinase in lead increases lipopolysaccharide-induced liver damage in rats. 1604 92


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