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)

Chronic liver damage induced by thioacetamide (TAM) was accompanied by changes in the expression of genes related to growth (beta-actin) and function (albumin and haptoglobin) of the liver. Their messenger RNA (mRNA) levels increased during the first days after TAM administration, but 4 to 7 days after prolonged treatment with this drug, liver gene expression was considerable decreased. TAM-induced changes in albumin and beta-actin mRNA levels were prevented by cotreatment with S-adenosyl-L-methionine (SAM). We have investigated the possible involvement of glutathione in the protective mechanism of SAM. Firstly, we found that TAM treatment in the rat induced changes in liver glutathione disulfide (GSSG) levels, with a concomitant increase in the glutathione reductase enzymatic activity, these changes being abolished when animals were cotreated with TAM and SAM. Secondly, when rats were pretreated with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, before thioacetamide administration, the beneficial effect of SAM on liver gene expression was completely abolished. These results were confirmed by assaying the alanine transaminase serum activity, a parameter of liver injury. TAM-treated animals had increases in this serum enzyme, this effect being partially blocked by SAM. However, in BSO-pretreated rats, the protective effect of SAM was impaired. Taking together all these results, we propose a glutathione-dependent mechanism in the SAM protection against TAM hepatotoxicity in the rat.
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PMID:Changes in rat liver gene expression induced by thioacetamide: protective role of S-adenosyl-L-methionine by a glutathione-dependent mechanism. 861 42

The influence of r-HuEPO on the activity of erythrocyte transketolase (ETKA), glutathione reductase (GSH) and glutamic-pyruvic transaminase (EGPT) was determined by spectrophotometry. 150 IU/kg BW/week of r-HuEPO was given i.v. during 2 months to 12 predialyzed uremics (PDU). Twenty healthy volunteers (HV) served as controls. GSH and EGPT activity were expressed as a coefficient. ETKA in HV = 2.39 +/- 0.10 and PDU = 1.53 +/- 0.10 mumol/ml/min differed significantly (p < 0.001). GSH in HV = 1.20 +/- 0.09 and PDU = 1.25 +/- 0.07, EGPT in HV = 1.20 +/- 0.10 and PDU = 1.38 +/- 0.11 differed significantly (p < 0.01 and p < 0.001, respectively). After 2 months of r-HuEPO treatment, ETKA, GSH and EGPT rose significantly (p < 0.01). Thus, r-HuEPO increases the activity of enzymes related with the content of vitamins B1, B2 and B6 in uremics.
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PMID:Recombinant human erythropoietin improves enzyme activity in erythrocytes of predialysis uremics. 867 97

The present study reports on the effects of horminone on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, on hepatic cytochrome P450 (P450) and cytochrome b5 (cyt b5) contents and on the activities of NADPH-cytochrome P450 reductase (NR), mixed function mono-oxygenases (MFO), glutathione-S-transferase (GST) and glutathione reductase (GR) of Wistar male rat. Horminone is a diterpenoid quinone (7,12-dihydroxyabiet-8,12-diene-11,14-dione) present in several species of the Labiatae family and used as medicinal plants in folk medicine. In this study, horminone was administered by the intraperitoneal route (i.p.) at a concentration of 1 or 10 mg/kg to each group of six mice, using water as a vehicle. On the one hand, results showed that horminone increased serum ALT and AST levels and cyt b5 content and induced the activities of ethylmorphine N-demethylase (EMD). On the other hand, horminone decreased P450 content and inhibited the activities of 7-ethoxyresorufin O-deethylase (ERD), 7-ethoxycoumarin O-deethylase (ECD), aniline 4-hydroxylase (AH) and NR. Based on these results, the possibility of toxic effects occurring after administration of plant extracts containing horminone must be considered.
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PMID:Effects of horminone on liver mixed function mono-oxygenases and glutathione enzyme activities of Wistar rat. 932 1

Cisplatin [cis-dichlorodiammineplatinum (II)] is a widely used chemotherapeutic drug that is toxic to the kidney. Concurrent administration of cysteine together with vitamin E, Crocus sativus and Nigella sativa reduced the toxicity of cisplatin in rats. When administered i.p. for 5 alternate days with 3 mg/kg cisplatin, cysteine (20 mg/kg) together with vitamin E (2 mg/rat) an extract of Crocus sativus stigmas (50 mg/kg) and Nigella sativa seed (50 mg/kg) significantly reduced blood urea nitrogen (BUN) and serum creatinine levels as well as cisplatin-induced serum total lipids increases. In contrast, the protective agents given together with cisplatin led to an even greater decrease in blood glucose than that seen with cisplatin alone. The serum activities of alkaline phosphatase, lactate dehydrogenase, malate dehydrogenase, aspartate aminotransferase and alanine aminotransferase of cisplatin-treated rats were significantly decreased, whereas the activities of glutathione reductase and isocitrate dehydrogenase were significantly increased. Addition of cysteine and vitamin E, Crocus sativus and Nigella sativa in combination with cisplatin partially prevented many changes in the activities of serum enzymes. In cisplatin-treated rats, the liver activities of isocitrate dehydrogenase and aspartate aminotransferase were significantly increased, whereas much greater changes were found in the kidneys, with increased activity of glucose-6-phosphate dehydrogenase and decreased activities of alkaline phosphatase, isocitrate dehydrogenase, malate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, sorbitol dehydrogenase and gamma-glutamyl transferase, as well as a decreased phosphorylation to oxidation ratio in the mitochondria, indicating reduced adenosine triphosphate production. Also, administration of cysteine and vitamin E, Crocus sativus and Nigella sativa together with cisplatin partially reversed many of the kidney enzymes changes induced by cisplatin. Cysteine together with vitamin E, Crocus sativus and Nigella sativa tended to protect from cisplatin-induced falls in leucocyte counts, haemoglobin levels and mean osmotic fragility of erythrocytes and also prevented the increase in haematocrit. The results of this study indicate a basis for the toxic effects of cisplatin, and suggest a possible way of counteracting the toxicity by introducing protective agents such sulphydryl compounds, other antioxidants and extracts of natural products. It also appears that cells adapt to the effects of cisplatin through the induction of systems that produce NADPH, which in turn compensates the decrease of free sulphydryl groups. We conclude that cysteine and vitamin E, Crocus sativus and Nigella Sativa may be a promising compound for reducing cisplatin-toxic side effects including nephrotoxicity.
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PMID:Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. 960 69

Male albino rats were intramuscularly administered a single dose of lead acetate (100 micromol/kg b.wt). Another group of rats were injected with sodium selenite (10 micromol/kg b.wt) before lead intoxication. After 3 and 24 hours, lead treatment resulted in significant increases in acid and alkaline phosphatases, GOT and GPT, total proteins, and cholesterol in serum. The total triglycerides in serum was decreased after 24 hours of intoxication. Lead treatment also produced significant elevation of lipid peroxidation in liver and kidney. The antioxidant capacity of hepatic and renal cells in terms of the activities of superoxide dismutase, glutathione reductase, and glutathione content was diminished. It appears from these results that lead may exert its toxic effect via peroxidative damage to renal and hepatic cell membranes after 24 hours. Selenium administration prior to lead injection produced pronounced prophylactic action against lead effects, and it is observed that selenium enhances the endogenous antioxidant capacity of the cells by increasing the activities of the superoxide dismutase and glutathione reductase and the glutathione content. As a result, the lipid peroxidation was decreased in both liver and kidney.
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PMID:Role of selenium against lead toxicity in male rats. 973 83

Alcohol and cocaine are abused by the general population as well as by pregnant women. Since alcohol and cocaine are hepatotoxic, pregnant mice were used to study the effect of alcohol and/or cocaine on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and on liver ultrastructure. Also, blood glutathione (GSH) and GSH related enzymes such as glutathione reductase (GSH-Rx) and glutathione peroxidase (GSH-Px) were studied. The mice were treated with 0.6 g/kg ethanol twice daily via gavage and/or 20 mg/kg of cocaine hydrochloride intravenously once daily. The treatment was from day 6 to 15 of gestation and these studies were performed at day 18. Our results indicated a significant increase in AST level after treatment with ethanol alone or in combination with cocaine. The blood GSH levels decreased significantly in all the treated groups compared to the control. The activity of GSH-Px was significantly decreased only in the ethanol and cocaine combination group compared to the control. Histopathological studies indicated that co-administration of ethanol and cocaine lead to a significant potentiation in liver toxicity as indicated by increased fatty infiltration.
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PMID:Effect of alcohol and/or cocaine on blood glutathione and the ultrastructure of the liver of pregnant CF-1 mice. 977 56

Enzyme activity modulation by cadmium in the liver of the teleost fish Sparus aurata was investigated in vivo following 3 and 6 days of CdCl2 administration (2.5 mg/kg body wt). The specific activities of the mitochondrial enzymes NAD-isocitrate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase were stimulated by approximately 20% after 3 days administration and were further increased (by about 40%) after 6 days treatment. In comparison with these enzymes, the activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) in mitochondria were less stimulated after the two indicated intervals of treatment. Cadmium significantly reduced the activities of liver cytoplasmic GOT and GPT while a simultaneous increase occurred in the serum activities of these same enzymes. The activity of liver NADPH-cytochrome P450 reductase was stimulated by 25 and 40% after 3 and 6 days cadmium intoxication, respectively. Lastly, the antioxidant enzymes glutathione peroxidase and glutathione reductase in liver and catalase in both liver and blood were strongly reduced after 3 and 6 days cadmium administration. These data suggest that cadmium in fish hepatocytes alters cell membrane structure and concomitantly induces some perturbation in the integrity of the mitochondrial membrane.
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PMID:Changes in liver enzyme activity in the teleost Sparus aurata in response to cadmium intoxication. 1033 Mar 29

The purpose of our study was to assess the effects of experimental dicroceliosis on the antioxidant defense capability of the liver in hamsters. Studies were carried out at 80 and 120 days after infection with an oral dose of 40 metacercariae of Dicrocoelium dendriticum. The parasitic pathology was ascertained by the presence of fluke eggs in feces, increased serum ALT and AST activities, and histological findings. The concentration of thiobarbituric acid-reactive substances (TBARS) and the ratio of oxidized to reduced glutathione (GSSG/GSH), measured as markers of oxidative stress, were significantly increased [TBARS: +40% and +84% at 80 and 120 days postinfection (p.i.), respectively; GSSG/GSH: +200% and +117%]. Dicroceliosis increased Se-dependent glutathione peroxidase (GPx) activity in both cytosol (+24% and +46%) and mitochondria (+73% and +41%). Superoxide dismutase activity was significantly reduced in cytosol (-19% and -38%) and mitochondria (-20% and -39%). No significant change was found in the activity of Se-independent GPx or catalase. The ratio of glutathione peroxidase/glutathione reductase at 80 and 120 days p.i. was increased by 25% and 63%, respectively. Gamma-glutamyl cysteinyl synthetase activity was increased by 27% and 20%, respectively. Our data indicate that although dicroceliosis courses with activation of antioxidant enzymes and glutathione synthesis, inefficient scavenging of reactive oxygen species takes place, resulting in oxidative liver damage.
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PMID:Oxidative stress and changes in liver antioxidant enzymes induced by experimental dicroceliosis in hamsters. 1034 40

Redox cycling metabolism of diquat catalyzes generation of reactive oxygen species, and diquat-induced acute hepatic necrosis in male Fischer 344 (F344) rats has been studied as a model of oxidant mechanisms of cell killing in vivo. At equal doses of diquat, female F344 rats sustained less hepatic damage than did male rats, as estimated by plasma alanine aminotransferase (ALT) activities after 6 h. Biliary efflux of glutathione disulfide (GSSG) was greater in male than in female rats at each dose of diquat, but even comparable rates of GSSG excretion were associated with less hepatic injury in female rats. Hepatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were similar in the two genders, and activities of glutathione reductase (GR) and glutathione S-transferase-alpha (GST-alpha) activities were higher in the male rats. Previous studies in male rats have implicated formation of 2,4-dinitrophenylhydrazine (DNPH)-reactive "protein carbonyls" and related iron chelate-catalyzed redox reactions as mechanisms critical to diquat-induced acute cell death in vivo. However, diquat-treated female rats showed higher levels of DNPH-reactive proteins in livers and in bile than did males, both at identical doses of diquat and at doses that produced similar elevations in plasma ALT activities. In female rats, fragmentation of hepatic deoxyribonucleic acids (DNA) was increased by doses of diquat that did not increase plasma ALT activities, and increased fragmentation was observed prior to elevation of plasma ALT activities. In the present studies, hepatic necrosis was most closely associated with DNA fragmentation, although additional studies are needed to determine the mechanisms responsible for and the pathophysiological consequences of the fragmentation.
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PMID:Sex differences in diquat-induced hepatic necrosis and DNA fragmentation in Fischer 344 rats. 1074 47

Repeated dosing of acetaminophen (paracetamol) to rats is reported to decrease their sensitivity to its hepatotoxic effects, which are associated with oxidative stress and glutathione depletion. We determined if repeated acetaminophen dosing produced adaptive response of key antioxidant system enzymes. Male rats (Sprague-Dawley, 10 weeks) were given 800, 1200, or 1600 mg/kg/day acetaminophen by oral gavage for 4 days. Liver was assayed for oxidative stress and antioxidant markers: malondialdehyde (MDA), thiobarbituric acid reactive substance (TBARS), total antioxidant status (TAS), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), catalase (CAT), and superoxide dismutase (SOD), and alanine transaminase (ALT) as a marker of hepatocellular injury. Acetaminophen at 1200/1600 mg/kg decreased GSH 26/47%, GPx 21/26%, CAT 35/28%, SOD 21/12%; and TAS 28/18% (correlated with CAT, r=0.91; SOD, r=0.66; GPx, r=0.45). Despite antioxidant deficiencies, and no TBARS change, MDA decreased 26%/33%/37% at 800/1200/1600 mg/kg, which correlated with increased GR (61%/62%/76%, r=0.77) and G6PD (130%/110%/190%, r=0.78). Both MDA (r=0.68) and G6PD (r=0.71) correlated with hepatic ALT, which decreased 27%/43%/48%, respectively. Resistance to acetaminophen hepatotoxicity produced by repeated exposure is partially attributable to upregulation of hepatic G6PD and GR activity as an adaptive and protective response to oxidative stress and glutathione depletion.
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PMID:Repeated acetaminophen dosing in rats: adaptation of hepatic antioxidant system. 1091 22


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