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)

Oxidative lipid metabolism as a result of acute cyanobacterial toxin-induced hepatotoxicity was monitored in male Sprague-Dawley rats using electron spin resonance (ESR) spectroscopy and image-guided proton nuclear magnetic resonance (1H-NMR) spectroscopy. ESR spectroscopy, coupled with spin trapping, was used to trap and detect lipid-derived radicals, formed in rat livers after acute in vivo exposure (LD50) to the cyanobacterial toxin, microcystin-LR (MCLR). A statistically significant increase in the levels (spectral peak integrals) of lipid radicals was detected in MCLR-treated livers (p < 0.05) (n = 8), in comparison to control livers (n = 6). In order to monitor lipid metabolism, before and for a period of 3 h, following toxin exposure, in vivo proton image-guided NMR spectroscopy was used. A statistically significant decrease in the levels of lipid methylene hydrogen resonances (spectral peak integrals) was observed from MCLR-treated livers (n = 6) 2 and 3 h post-exposure (p < 0.05), in comparison to controls (n = 6). Image-guided NMR spectroscopy was also used to detect significant decreasing levels of in vivo glutamine/glutamate, following exposure to MCLR. Biochemical assessment of perchloric extracts of liver glutamine and glutamate levels correlated with NMR spectroscopy results. Lactate levels measured as perchloric acid extracts, were also found to significantly decrease. In addition, assessment of serum enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were used to confirm hepatotoxicity (n = 20). This study strongly suggests that oxidative stress related processes are involved in in vivo microcystin-induced hepatotoxicity in mammals, and may play an integral role in MCLR-induced toxicity.
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PMID:Assessment of in vivo oxidative lipid metabolism following acute microcystin-LR-induced hepatotoxicity in rats. 1199 4

The effects of cPrG x HCl and epirubicin on the suppression of cell growth were examined on human breast cancer cell line (MDA-MB-231). Either cPrG x HCl or epirubicin alone showed a tumor growth inhibition in a time- and dose-dependent manner, however, the combinatory use of cPrG x HCl together with epirubicin resulted in prominent synergistic effects on the breast cancer cells. In the in vitro studies, the combinatory use of these two drugs accelerated apoptotic cell death as revealed by morphological changes as well as by the appearance of subG1 population by flow cytometry. In addition, confocal microscopy revealed that the accumulation of epirubicin in nucleus increased apparently when cPrG x HCl were present. In the in vivo assay, nude mice bearing xenografted tumor cells received 4 weeks of intraperitoneal administration of cPrG-HCl and epirubicin. After 12 days, the combinatory treatment significantly suppressed the tumor growth compared to the controls. The TUNEL staining revealed that tumor cells in cPrG x HCl plus epirubicin-treated mice exhibited a higher apoptotic rate. In addition, 31P-NMR studies on the xenografted tumor revealed that cPrG x HCl lowered tumor pHi (below pH 6.9). while it did not affected muscle pHi. No pathological changes were observed in any intrinsic organs and the serum alanine aminotransferase levels remained within normal limits among the groups. These results suggest that the combinatory use of cPrG x HCl and epirubicin may be useful for breast cancer therapy.
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PMID:Synergistic effects induced by cycloprodigiosin hydrochloride and epirubicin on human breast cancer cells. 1200 Feb 16

Hypercreatinuria is a well-known feature of liver and testicular toxicity and we have recently proposed that hepatotoxin-induced hypercreatinuria would arise as a consequence of increased cysteine synthesis associated with the provision of protective substances (glutathione and/or taurine). Here a direct relationship between hepatotoxin-induced hypercreatinaemia and hypercreatinuria is shown and the possible relationships of hepatotoxin-induced hypercreatinaemia and hypercreatinuria to hepatic damage and to weakened nutritional status are examined. Male Sprague-Dawley rats were dosed with a variety of model hepatotoxins at two dose levels per toxin. Blood plasma samples taken at 24 h post-dosing and urine samples collected from 24-31 h post-dosing were analysed by (1)H NMR spectroscopy. Both hypercreatinaemia and hypercreatinuria were found in rats dosed with allyl formate (75 mg/kg), chlorpromazine (30 and 60 mg/kg), alpha-naphthylisothiocyanate (ANIT, 100 mg/kg) and thioacetamide (200 mg/kg), whilst significant hypercreatinuria, but not hypercreatinaemia, was found after dosing with thioacetamide (50 mg/kg). Neither hypercreatinaemia nor hypercreatinuria were found after dosing with allyl formate (25 mg/kg), ethionine (300 and 1000 mg/kg) or ANIT (30 mg/kg). Reduced feeding is known to cause hypercreatinuria in rats and, of the four hepatotoxins that induced hypercreatinaemia and hypercreatinuria at the given time-points, two, chlorpromazine and ANIT, also affected nutritional status with ketosis being clearly identifiable from the plasma (1)H NMR spectra. Thus, the creatine changes induced by ANIT and chlorpromazine are potentially attributable, in whole or in part, to reduced feeding rather than to liver effects alone and, consequently, the results were examined with and without inclusion of the ANIT and chlorpromazine data. With all of the data included, there were eight out of ten points of correspondence between the incidence of hypercreatinaemia and/or hypercreatinuria and the incidence of increases in plasma alanine aminotransferase (ALT) activity. At the same time there were nine out of ten points of correspondence between the incidence of hypercreatinaemia and/or hypercreatinuria and the incidence of increases in plasma aspartate aminotransferase (AST) activity. However, with the ANIT and chlorpromazine data excluded there was complete (six out of six points) correspondence between the incidence of hypercreatinaemia and/or hypercreatinuria and the incidence of increases in plasma AST and ALT in the remaining data. Likewise, with all of the data included, there was some apparent correlation (correlation coefficient, r=0.80) between the group mean levels of plasma AST and plasma creatine when expressed relative to the mean values for controls sampled at the same time-point. However, with the ANIT and chlorpromazine data excluded, that correlation coefficient was increased to 0.95. The findings of these studies suggest that the ANIT- and chlorpromazine-induced creatine changes may have been caused by reduced feeding rather than by liver toxicity. The allyl formate and thioacetamide data indicate that hepatocellular necrosis is accompanied by increases in plasma and urinary creatine, and suggest the possibility of a quantitative relationship between the increases in plasma AST and the increases in plasma creatine that are associated with hepatocellular necrosis. The ethionine and ANIT data suggest that fatty liver (steatosis) and cholestatic damage may not be associated with hypercreatinaemia and hypercreatinuria.
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PMID:Hepatotoxin-induced hypercreatinaemia and hypercreatinuria: their relationship to one another, to liver damage and to weakened nutritional status. 1452 May 8

Steatotic livers are highly susceptible to I/R (ischaemia/reperfusion) injury and, therefore, the aim of the present study was to evaluate the in vivo effect of NAC (N-acetylcysteine) on hepatic function in the early and initial late phase of warm liver I/R injury in steatotic rabbits. Twelve New Zealand White rabbits were fed a high-cholesterol (2%) diet. The control group (n=6) underwent lobar liver ischaemia for 1 h, followed by 6 h of reperfusion. In the treated group receiving NAC (n=6), an intravenous infusion of NAC was administered prior to and during the 6 h reperfusion period. Systemic and hepatic haemodynamics were monitored continuously. ALT (alanine aminotransferase) activity and bile production were measured. NMR spectroscopy was used to analyse bile composition. Oxidation of DHR (dihydrorhodamine) to RH (rhodamine) was used as a marker of production of reactive oxygen and nitrogen species. Moderate centrilobular hepatic steatosis was demonstrated by histology. The results showed that NAC administration significantly improved portal flow, hepatic microcirculation, bile composition and bile flow after 5 h of reperfusion. NAC administration was also associated with less hepatocellular injury, as indicated by ALT serum activity, and decreased the oxidation of DHR to RH. In conclusion, NAC administration decreased the extent of I/R injury in the steatotic liver, particularly during the late phase of reperfusion.
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PMID:N-Acetylcysteine ameliorates the late phase of liver ischaemia/reperfusion injury in the rabbit with hepatic steatosis. 1598 89

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

Oral administration of alcoholic extracts of Schouwia thebica Webb showed that extracts are safe for human use. The studied extracts are considered safe, since they failed to induce death of mice in doses up to 4000 mg/kg body weight. Hepatoprotective activity was studied for the total alcoholic extracts. The total extract was fractionated in turn with diethyl ether, chloroform, ethyl acetate, and n-butanol, respectively. These extracts were tested for possible hepatoprotective activity. It was found that the ethyl acetate and n-butanol extracts of S. thebica Webb showed hepatoprotective activity. These extracts significantly reduced the increase in activities of ALT, AST, and GGT, and levels of glucose, triglycerides, and cholesterol in serum of CCl(4)-treated rats. The extracts showing activity were found to contain flavonoids; one new compound, chrysoeriol-7-O-xylosoide- (1,2)-arabinofuranoside (2), in addition to another known four compound chrysoeriol (1), quercetin (3), quercetin-7-O-rhamnoside (4), and kaempferol-3-O-beta-D-glucoside (5). The isolated new compound was mainly found to be responsible for this activity when tested on animals in the laboratory. The structures were established by melting point, UV spectroscopy, EI-Mass, Fab-Mass, and 1D and 2D NMR spectroscopic techniques on a 600MHz instrument.
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PMID:Hepatoprotective activity of Schouwia thebica webb. 1679 83

Cochlospermum vitifolium (Willd.) Sprengel is a Mexican medicinal plant that is used in the folk medicine for the treatment of hypertension, diabetes, hepatitis and related diseases. The purpose of the present study was to assess the pharmacological properties of different extracts from Cochlospermum vitifolium bark as potential agent for the treatment of some factors related with metabolic syndrome (MS), a complex disease produced for several pathophysiological factors such as visceral fat obesity, insulin resistance, hypertension, dyslipidemia and liver steatosis. Hexane (HECv), dichloromethane (DECv) and methanol (MECv) extracts were subjected to some pharmacological assays to determine their vasorelaxant and hypoglycemic activity. On the other hand, MECv was also evaluated to determine its hepatoprotective effect on sub-chronic experimental assay. HECv showed a significant endothelium-independent relaxation on rat aorta rings (intact endothelium: IC(50)=14.42+/-5.90 microg/mL, E(max)=92.71+/-8.9%; denuded endothelium: IC(50)=27.94+/-4.0 microg/mL, E(max)=78.68+/-4.6%) and MECv produced an endothelium-dependent relaxation (IC(50)=21.94+/-6.87 microg/mL, E(max)=79.12+/-7.80%) on this tissue. Furthermore, HECv (at a dose of 120 mg/kg) also showed a significant decrease of blood glucose levels (p<0.05) on normoglycemic rats. Moreover, MECv (at a dose of 100 mg/kg) also was administered to bile duct-obstructed rats to determine its hepatoprotective activity, showing a statistically significant decrease of serum glutamic-pyruvic transaminase (PGT, 45%) and alkaline phosphatase (APh, 15%) (p<0.05). Finally, we obtained a crystalline polyphenolic compound from MECv by spontaneous precipitation. Those crystals were identified as (+/-)-naringenin by X-ray diffraction, NMR, IR and GC-MS techniques. Results suggest that Cochlospermum vitifolium could be used as a potential agent against MS since it shows hypoglycemic, vasorelaxant and hepatoprotective properties.
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PMID:Hypoglycemic, vasorelaxant and hepatoprotective effects of Cochlospermum vitifolium (Willd.) Sprengel: a potential agent for the treatment of metabolic syndrome. 1697 15

Acetaminophen (APAP) is one of the most commonly used drugs for the safe and effective treatment of fever and pain. However, it is a well-established hepatotoxin. The objective of this study was to identify alternation in various genes in liver of mice after administration of low and high doses of APAP. Male C57BL/6J mice received APAP (30 or 300 mg/kg, i.p.). They were sacrificed after 6 hr and 24 hr for assessment of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total RNA isolation, cDNA microarray analysis and histopathological analysis of liver injury. Low dose of APAP did not cause hepatotoxicity in mice. However, it was toxic at a high dose. Using microarray technology, we selected changed genes more than 1.5 fold. Gene expression changes were recorded even at a low dose treatment with APAP. Six (6) hr after APAP treatment at low dose, 6 genes were up-regulated and 25 genes were down-regulated. However, 24 hr after treatment at low dose 8 genes were up-regulated and 34 genes were down-regulated. 6 hr after of high dose treatment 29 genes were down-regulated and none was up-regulated. A 24 hr treatment with high dose up-regulated 6 genes and down-regulated 18 genes. These expression patterns provide information on high versus low dose mechanisms of APAP toxicity. Gene expression signatures recorded after a nontoxic dose of APAP strongly support the validity of gene expression changes as meaningful markers of hepatotoxicity.
Physiol Chem Phys Med NMR 2006
PMID:Effects of acetaminophen on hepatic gene expression in mice. 1847 68

Isolated rat hearts were studied by (31)P NMR and (13)C NMR. Hyperpolarized [1-(13)C]pyruvate was supplied to control normoxic hearts and production of [1-(13)C]lactate, [1-(13)C]alanine, (13)CO(2) and H(13)CO(-) (3) was monitored with 1-s temporal resolution. Hearts were also subjected to 10 min of global ischemia followed by reperfusion. Developed pressure, heart rate, oxygen consumption, [ATP], [phosphocreatine], and pH recovered within 3 min after the ischemic period. During the first 90 s of reperfusion, [1-(13)C]alanine and [1-(13)C]lactate appeared rapidly, demonstrating metabolism of pyruvate through two enzymes largely confined to the cytosol, alanine aminotransferase, and lactate dehydrogenase. (13)CO(2) and H(13)CO(-) (3) were not detected. Late after ischemia and reperfusion, the products of pyruvate dehydrogenase, (13)CO(2) and H(13)CO(-) (3) were easily detected. Using this multinuclear NMR approach, we established that during the first 90 s of reperfusion PDH flux is essentially zero and recovers within 20 min in reversibly-injured myocardium.
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PMID:Inhibition of carbohydrate oxidation during the first minute of reperfusion after brief ischemia: NMR detection of hyperpolarized 13CO2 and H13CO3-. 1895 54

In social hornets of sub-family Vespinae there are stripes or areas in the cuticle which are endowed with a bright color (yellow, orange, green) that is different from the customary native brown color. In these brightly colored areas, the middle and bottom layers of the cuticle contain a yellow-colored filling material instead of the ordinary lamellae of which the cuticle is comprised. At high magnification, most of the yellow matter is seen to be made up of yellow granules interlinked by string-like threads. Apart from yellow granules, hemolymph and a surrounding cuticle, these areas are also found to contain glucose, iron and triglycerides as well as enzymes like GOT, GPT, CPK and LDH, in high concentrations that vary considerably from those in vespan hemolymph and whose levels are different under illumination than in the dark. Such high levels of enzymes suggest first an association with liver function activities, and secondly, that the difference in their levels when exposed to light and when subjected to darkness is indicative of the influence of the energy of light upon them.
Physiol Chem Phys Med NMR 2007
PMID:Some qualitative liver functions in hornet yellow cuticle. 1925 56


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