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

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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)

The popular seafood squid contains high levels of naturally occurring amines such as dimethylamine (DMA) trimethylamine and trimethylamine-N-oxide (TMAO). The hepatotoxicity and hepatocarcinogenicity of squid with or without exogenous nitrite were investigated in rats. Acute necrosis including polymorphogenic neutrophil infiltration, haemorrhage and cholangiofibrosis were observed in the livers of most rats fed squid. Hepatocellular carcinoma (HCC) was induced in two out of 12 rats (16%) by feeding 10% squid in Purina rat chow for 10 months. The incidence of HCC was increased to four out of 10 rats (33%) when 0.3% NaNO2 was added to the above diet. At the end of the experiment a marked elevation of serum gamma-glutamate transferase was observed in treated groups, but no significant changes in the activities of serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were detected. Vitamin C (0.3%) gave partial protection against hepatic damage. The concentration of DMA in squid is estimated to be 0.19%; this concentration did not induce HCC under the experimental conditions used. Therefore it is suggested that another major naturally occurring amine in squid, TMAO, could be one of the important factors involved in the induction of hepatotoxicity and hepatocarcinogenicity in rats.
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PMID:Hepatotoxicity and hepatocarcinogenicity in rats fed squid with or without exogenous nitrite. 132 3

The purpose of this study was to estimate the effects of lipid peroxidation in regenerating rat liver. Partial 70% hepatectomy was performed in rat according to Higgings and Anderson. EPC (alpha Toc: Ascorbic acid = 6:4, radical scavenger) was injected intravenously (5mg/kg weight) one hour before operation. Lipid peroxidation in regenerating liver reached a peak at 24 hours after operation. The administration of EPC markedly suppressed the increase of lipid peroxide in the plasma and remnant liver and that of GPT after hepatectomy, with subsequent good liver regeneration ratio. Moreover, the pretreatment with EPC remarkably elevated the activity of thymidine kinase (index of DAN synthesis). The EPC administration had not notable effects on the level of plasma ketone body ratio in animal but pathologically caused early advent of glycogen granule in the remnant liver tissue after partial hepatectomy, which reflected restoration of mitochondrial energy level. The results of the present study suggest that scavenger may be useful not only for impairment of liver dysfunction but also for recovery of mitochondrial energy level and DNA synthesis after liver resection.
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PMID:[Investigation of lipid peroxidation in regenerating rat liver]. 143 8

2-Bromo-(diglutathion-S-yl)hydroquinone [2-Br-(diGSyl)HQ] causes severe necrosis of the proximal renal tubules in the rat, elevations in blood urea nitrogen (BUN) and increased urinary excretion of protein, glucose, and lactate dehydrogenase. In contrast, 2-Br-3-(GSyl)HQ, 2-Br-5-(GSyl)HQ, and 2-Br-6-(GSyl)HQ caused differentially less toxicity than the diglutathionyl conjugate. None of these conjugates had any apparent effect on liver pathology and serum glutamate-pyruvate transaminase remained within the normal range. Pretreatment of rats with probenecid, an organic anion transport inhibitor, offered only slight protection against 2-Br-(diGSyl)HQ-mediated elevations in BUN, proteinuria, or glucosuria. In contrast, quinine, an organic cation transport inhibitor, potentiated the nephrotoxicity of 2-Br-(di-GSyl)HQ. Thus, in contrast to other nephrotoxic sulfur conjugates, probenecid-sensitive organic ion transport systems do not contribute to the kidney-specific toxicity of 2-Br-(diGSyl)HQ. However, inhibition of renal gamma-glutamyl transpeptidase by AT-125 completely protected rats from the nephrotoxic effects of 2-Br-(diGSyl)HQ. Aminooxyacetic acid, an inhibitor of cysteine conjugate beta-lyase, caused a 20-25% decrease in 2-Br-(diGSyl)HQ-mediated elevations in BUN and urinary excretion parameters. The isomeric 35S conjugates covalently bound to rat kidney 10,000 x g homogenate in the order 2-Br-6-(GSyl)HQ greater than 2-Br-5-(GSyl)HQ greater than 2-Br-3-(GSyl)HQ greater than 2-Br-(diGSyl)HQ. AT-125 (0.4 mM) decreased covalent binding by 25%, 17%, 33%, and 28%, respectively. Aminooxyacetic acid (0.1 mM) inhibited covalent binding by 26%, 10%, 17%, and 17% respectively. Ascorbic acid (1.0 mM) inhibited covalent binding by 63%, 87%, 62%, and 28%, respectively, and this inhibition correlated, inversely, with the redox potential of the conjugates. Thus, the covalent binding is mediated preferentially by oxidation of the quinol moiety, although the formation of reactive thiols cannot be excluded. In addition, the initial conjugation of 2-BrHQ with GSH does not result in the formation of a less redox-active species. However, the subsequent addition of a second molecule of GSH results in the formation of a more redox-stable compound, which, paradoxically, enhances toxicity. The metabolism of 2-Br-(diGSyl)HQ by renal proximal tubular gamma-glutamyl transpeptidase and trans-membrane transport of the cysteine conjugate(s) followed by oxidation of the quinol moiety is probably responsible for the target organ toxicity of this compound.
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PMID:2-Bromo-(diglutathion-S-yl)hydroquinone nephrotoxicity: physiological, biochemical, and electrochemical determinants. 317 33

The oral treatment of rats with sodium ascorbate in combination with sodium nitrite and aminopyrine prevents the rise in serum alanine aminotransferase (EC 2.6.1.2) observed when nitrite and aminopyrine are given alone. Ascorbic acid also affords protection, whereas dehydroascorbic acid exerts no protective effect.
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PMID:Protective effect of ascorbic acid on hepatotoxicity caused by sodium nitrite plus aminopyrine. 451 87

Administration of large doses of acetaminophen or cocaine to male CD-1 mice produces significant hepatic injury with marked elevation in serum glutamate-pyruvate transaminase activity and severe hepatocellular necrosis. The proposed mechanism for this phenomenon is activation of both parent compounds to hepatotoxic metabolites. Ascorbic acid, 1 g/kg, given to mice 1 hour before and 1 hour after either acetaminophen or cocaine treatment prevented development of the severe hepatocellular damage observed with administration of either drug alone. Plasma disappearance of acetaminophen was less rapid in ascorbic acid-treated animals, suggesting that in vivo metabolism of acetaminophen was altered by ascorbic acid treatment. However, ascorbic acid treatment alone produced a modest decrease in hepatic glutathione content and did not prevent marked hepatic glutathione depletion when administered concomitantly with acetaminophen. Furthermore, a 2-mM ascorbic acid concentration did not alter in vitro hepatic microsomal metabolism of cocaine as measured by formaldehyde formation. While the mechanism(s) for its protective effect remains to be elucidated, these results raise the possibility that ascorbic acid may be useful in preventing hepatic injury caused by some hepatotoxic drugs.
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PMID:Ascorbic acid protects against acetaminophen- and cocaine-induced hepatic damage in mice. 651 Feb 39

The in vivo effects of ascorbic acid on the reoxygenated liver tissue were examined, with regard to the following effects: (i) the effects of scavenging radicals and/or reducing peroxidative reactions, and (ii) the effects of the chelation with low-molecular-weight iron and increasing its reactivity (radical production). Ascorbic acid is one of the water-soluble vitamins known to have various physiological effects involving both chelating and reducing properties at once. Lipid peroxidation of the reoxygenated liver tissue estimated by the production of TBARS (thiobarbituric acid-reactive substance) and LPO (lipid hydroperoxides) was suppressed effectively by the preischemic intraperitoneal administration of ascorbic acid. Ascorbic acid also showed this anti-oxidant effect in a dose-dependent manner. The analysis of the levels of ascorbic acid and glutathione of the liver tissue revealed that ascorbic acid works as an anti-oxidant probably by being oxydized finally to dehydroascorbic acid just after the reoxygenation. The latter was reduced to ascorbic acid again, coupled with the conversion of GSH to GSSG in the postischemic time course. The predominant effect of ascorbic acid on the reoxygenated liver tissue seems to be caused by the scavenging radicals and/or reducing peroxidative reactions, rather than by chelating iron and increasing its reactivity (radical production). Cellular integrity (estimated by the release of GOT, GPT, and LDH) and the energy state of the postischemic liver tissue (estimated by the tissue ATP level) were also well preserved by the administration of ascorbic acid.
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PMID:The in vivo cytoprotection of ascorbic acid against ischemia/reoxygenation injury of rat liver. 773 75

p-Aminophenol (PAP) is a widely used industrial chemical and a metabolite of analgesics, such as acetaminophen (APAP). It was found recently that PAP, a known nephrotoxicant, could cause acute hepatotoxicity in mice but not in rats. The mechanism of hepatotoxicity is not known. The aim of this study was to investigate the role of N-acetylation of PAP to APAP in PAP-induced toxicity. Male C57BL/6 mice injected intraperitoneally (i.p.) with various doses of PAP were sacrificed at 12 hours for measurement of serum glutamic-pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) levels and determination of the extent of hepatic nonprotein sulfhydryl (NPSH) and glutathione (GSH) depletion. Plasma levels of APAP and its metabolites were measured by HPLC after PAP administration. p-Aminophenol depleted NPSH in a dose- and time-dependent manner. Depletion of NPSH in mouse liver occurred at PAP doses above 400 mg/kg. Buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, potentiated the PAP-induced hepatotoxicity. Ascorbate, a reducing agent, did not affect PAP-induced hepatotoxicity and NPSH depletion. After PAP treatment, APAP and its sulfate and glucuronide conjugates as well as GSH conjugates (APAP-cysteine and APAP-mercapturate) were detected in the plasma. The results suggest the roles of GSH and N-acetylation of PAP to APAP in PAP-induced hepatotoxicity.
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PMID:p-Aminophenol-induced liver toxicity: tentative evidence of a role for acetaminophen. 1117 Mar 13

This study was undertaken to evaluate the effectiveness of L-ascorbic acid (AA) in alleviating the toxicity of aflatoxin B1 (AFB1) in male New-Zealand white rabbits. Five rabbits (6 months of age and mean body weight 3.12 kg) per group were assigned to 1 of 6 treatment groups: 0 mg AA and 0 mg AFB1/kg BW (control); 20 mg AA/kg BW; 15 microg AFB1/kg BW; 15 microg AFB1 plus 20 mg AA/kg BW; 30 pg AFB1/kg BW; 30 pg AFB1 plus 20 mg AA/kg BW. Rabbits were orally administered their respective doses every other day for 9 weeks, followed by a 9-week recovery period where all drugs were withdrawn. Evaluations were made for hemato-biochemical parameters and enzymatic activities. Results showed that AFB1 significantly (p < 0.05) decreased hemoglobin (Hb), total erythrocytic count (TEC) and packed cell volume (PCV), in a dose-dependent manner, and these effects were continued during the recovery period. Ascorbic acid caused an increase in these parameters, and alleviated the negative effect of AFB1 during the treatment period. Additionally, serum concentrations of total protein, albumin and glucose were significantly (P < 0.05) declined by treatment with the high dose of aflatoxin and these effects were continued during the recovery period. Ascorbic acid caused non-significant increases in these parameters and alleviated the harmful effect of AFB1. On the other hand, aflatoxin treatment caused significant increases (P < 0.05) in the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AlP) during the treatment period in a dose dependent manner, and this effect was continued during the recovery period, especially with the high dose. Also, treatment with the high dose of aflatoxin caused significant increases (P<0.05) in cholesterol and total bilirubin. Ascorbic acid caused significant decreases in these parameters and alleviated the harmful effects of AFB1. Whereas, Total leukocyte count (TLC), urea and creatinine were not significantly affected by aflatoxin-treatment. Generally, it is interesting feature that the treatment with AA alone had no negative effects on most of the previous parameters. Also, the presence of AA could diminished the adverse effects of AFB1 on most of hematological and biochemical values, and enzymatic activities in rabbits.
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PMID:Influence of ascorbic acid supplementation on the haematological and clinical biochemistry parameters of male rabbits exposed to aflatoxin B1. 1261 57

By breeding and feeding salt to spontaneously hypertensive rats (SHR) continuously over a long period (until 60 wk old), rats with systolic blood pressures (SBP) of over 270 mmHg were prepared. It was studied whether or not supplying large amounts of vitamin C (200 mg/rat/d) over this period might bring any beneficial effect to blood pressure. Moreover, physico-chemical studies were performed to measure the components and enzymes in the blood and urine at 53 and 60 wk-old, and biochemical studies on vitamin C were also carried out in this experiment. Male (14 rats: 7 wk-old, 100-105 g) and female (15 rats: 7 wk-old, 95-100 g) SHR were divided into three groups and bred continuously for 53 wk. The A group rats were given salt (2.5 g/100 g of diet), the B group rats were given salt and vitamin C (500 mg/100 mL of drinking water), and the C group rats were controls. The results showed almost the same tendencies between male and female rats. The body weights of the SHR in groups A and B were slightly lower than group C. The amount of food intake in groups A and B was almost the same as group C. The amount of water intake was, in the order from highest to lowest, group A, B and C. The SBP of group A rats exhibited the highest value among the three groups. The SBP of group B rats given vitamin C simultaneously with the salt resulted in a low blood pressure level close to that of the controls (group C). Furthermore, the DBP (diastolic blood pressure) also reflected the antihypertensive effect of vitamin C as well. The heartbeat of the rats was highest in group A, and was comparable to the value in the rats receiving vitamin C simultaneously with salt. For the tests on occult blood and protein in the urine, group A rats showed strong positive reactions, whereas the group B and C rats had decreased results for both tests. The organ weights of the liver, stomach, spleen, adrenal gland and kidneys per 100 g rat body weight were not different among the three groups. The values for the bilirubin content, and the enzyme activities of ALT and AST in the blood showed to be the highest in the male rats of group A. The values from the group B rats decreased near to the normal value like the control group. Vitamin C was found to decrease the blood pressure in SHR, and also to work effectively to protect liver and kidney functions even under the condition of very high blood pressure, as high as 250 mmHg.
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PMID:Effects of vitamin C on high blood pressure induced by salt in spontaneously hypertensive rats. 1470 3

For a long time, aluminium (Al) has been considered an indifferent element from a toxicological point of view. In recent years, however, Al has been implicated in the pathogenesis of several clinical disorders, such as dialysis dementia, the fulminant neurological disorder that can develop in patients on renal dialysis. Therefore, the present experiment was carried out to determine the effectiveness of l-ascorbic acid (AA) in alleviating the toxicity of aluminium chloride (AlCl3) on certain hemato-biochemical parameters, lipid peroxidation and enzyme activities of male New Zealand white rabbits. Six rabbits per group were assigned to 1 of 4 treatment groups: 0mg AA and 0mg AlCl3/kg body weight (BW) (control); 40 mg AA/kg BW; 34 mg AlCl3/kg BW (1/25 LD50); 34 mg AlCl3 plus 40 mg AA/kg BW. Rabbits were orally administered their respective doses every other day for 16 weeks. Evaluations were made for lipid peroxidation, enzyme activities and hemato-biochemical parameters. Results obtained showed that AlCl3 significantly (P<0.05) induced free radicals and decreased the activity of glutathione S-transferase (GST) and the levels of sulfhydryl groups (SH groups) in rabbit plasma, liver, brain, testes and kidney. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AlP), acid phosphatase (AcP), and phosphorylase activities were significantly decreased in liver and testes due to AlCl3 administration. While, plasma, liver, testes and brain lactate dehydrogenase (LDH) activities were significantly increased. Contrariwise, the activity of acetylcholinesterase (AChE) was significantly decreased in brain and plasma. Aluminium treatment caused a significant decrease in plasma total lipids (TL), blood haemoglobin (Hb), total erythrocytic count (TEC) and packed cell volume (PCV), and increased total leukocyte count (TLC) and the concentrations of glucose, urea, creatinine, bilirubin and cholesterol. Ascorbic acid alone significantly decreased the levels of free radicals, TL, cholesterol, glucose and creatinine, and increased the activity of GST, SH groups, Hb, TEC and PCV. While, the rest of the tested parameters were not affected. Also, the present study showed that ascorbic acid can be effective in the protection of aluminium-induced toxicity.
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PMID:Aluminium-induced changes in hemato-biochemical parameters, lipid peroxidation and enzyme activities of male rabbits: protective role of ascorbic acid. 1512 98


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