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)

Following oral administration of luteoskyrin (LS), a bis-anthraquinone and hepatocarcinogenic mycotoxin of Penicillium islandicum Sopp, to ddY male mice, significant increases in serum GOT and GPT activities, 8-hydroxydeoxyguanosine (8-OH-dG) residues in hepatic DNA, and hepatic lipid peroxide level were observed. alpha-Tocopherol (alpha-TP) depressed the hepatic lipid peroxide content but did not decrease the 8-OH-dG level. These findings indicate that hydroxy radicals derived from LS are involved in the peroxidation of hepatic lipids followed by liver injury, and that the hydroxylation reaction of deoxyguanosine (dG) residues of hepatic DNA at the 8-position was unsusceptible to alpha-TP.
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PMID:Formation of the 8-hydroxydeoxyguanosine moiety in hepatic DNA of mice orally administered with luteoskyrin, a bis-anthraquinoid mycotoxin. 195 24

8-Hydroxydeoxyguanosine (oh8dG) is a promutagenic DNA lesion produced by oxygen radicals. We examined alterations in the oh8dG level in human livers which have chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The oh8dG content in livers with chronic hepatitis was significantly higher than the oh8dG content in normal livers (P < 0.05). There was also a significant correlation between the oh8dG content in noncancerous liver tissues with individual serum alanine aminotransferase concentration (r = 0.515; P < 0.001). Thus, chronic inflammation in the liver produces oxidative DNA damage, which may increase the risk for genomic alterations causing hepatocarcinogenesis.
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PMID:Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis. 820 35

Hemochromatosis is characterized by pathologic iron overload which often leads to various pathological conditions. The mechanism by which excess iron induces these conditions is not clearly understood. Using rats as the model, this investigation was conducted to explore the mechanism of toxicity associated with iron overload. Sprague-Dawley male rats were fed a 3% carbonyl iron-supplemented diet for eight weeks to achieve iron accumulation. Liver iron reached approximately 2 mg/g which is more than 16 times the control values (mean +/- SD, 0.12 +/- 0.02 mg/g, p < 0.001). Serum iron was consistently higher in the experimental rats (mg/L): 3.41 +/- 0.58 versus 1.89 +/- 0.18, p < 0.001. The high levels of iron accompanied enhanced oxidative damage in the hepatic nuclear DNA when 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured as a product of DNA oxidation. The levels of 8-OHdG in the experimental samples were significantly higher than the controls (8-OHdG X 10(-5)/dG): 4.22 +/- 1.82 versus 1.84 +/- 0.33, p < 0.05. The results of serum enzyme assays suggest that iron overload caused mild hepatocellular damage: alanine transaminase significantly increased; lactate dehydrogenase did not change; alkaline phosphatase decreased. Since the accumulation of 8-OHdG in the nuclear DNA is highly deleterious to cells, these data suggest oxidative damage in the nuclear DNA may be a critical factor in inducing diseases associated with iron overload.
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PMID:Toxicity associated with iron overload found in hemochromatosis: possible mechanism in a rat model. 1034 1

Extract of Salvia Miltiorrhiza (SM) has been widely used in traditional Chinese medicine for treating liver diseases. Recent experimental evidence indicates that it has anti-tumor potential. In this study, the effect of SM on alfatoxin B1 (AFB1)-induced hepatocarcinogenesis was investigated in male Fischer 344 rats. AFB1 (40 microg/100 g body wt, by gavage) was administered once a week for 24 weeks. In SM treatment group, rats were given SM (0.25g/100g body wt, 5 days/week by gavage) for a total of 28 weeks, including 4 weeks before and 24 weeks during AFB1 exposure. Results showed that the elevation of serum alanine aminotransferase and aspartate aminotransferase activities due to AFB1 dosing was almost completely abolished by the treatment of SM, indicating that SM could prevent AFB1-induced liver cell injury. It was further observed that SM substantially reduced glutathione S-transferase placenta form (GST-P) positive foci formation and GST-P mRNA expression caused by AFB1, which clearly suggests that SM is effective in preventing AFB1-induced hepatocarcinogenesis. Furthermore, the inhibition on AFB1 hepatocarcinigenesis was associated with a corresponding decrease in AFB1-DNA adducts formation as well as AFB1-induced oxidative DNA damage (8-hydroxydeoxyguanosine) in rat liver. Our results also indicate that the protective effect of SM might be mediated through dual mechanisms: (i) the enhancement of AFB1 detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM.
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PMID:Protection of salvia miltiorrhiza against aflatoxin-B1-induced hepatocarcinogenesis in Fischer 344 rats dual mechanisms involved. 1144 22

Patients with porphyria cutanea tarda (PCT) develop hepatocellular carcinoma as a late consequence. Pre-loading of C57BL/10ScSn mice with iron greatly sensitizes them to the induction of hepatic porphyria caused by hexachlorobenzene (HCB). HCB will also cause liver tumors in experimental animals. Elevated liver iron stores are implicated in the development of some human liver cancers in connection with its known catalytic role in generation of highly reactive activated oxygen species. The aim of this study was to determine the lipid and DNA oxidative damage in iron and HCB-induced porphyric mice. C57BL/10ScSn mice received i.p. injections of dextran sulfate (control), iron (Imferon) or combined iron and HCB. 6 weeks after treatment plasma ALT levels and hepatic free iron, porphyrin, lipid peroxides and 8-hydroxyguanosine (8-OHdG) levels were analyzed. Hepatic porphyrin level was significantly (p < 0.001) increased following combined iron/HCB treatment as compared to control mice. The level of lipid peroxides increased 9-fold (p = 0.001) and 35-fold (p < 0.001) after iron and iron/HCB treatment respectively, whereas the level of 8-OHdG was increased 2.5-fold (p = 0.002) and 7.5-fold (p < 0.001) after iron and iron/HCB treatment respectively as compared to control mice. The authors conclude that iron overload in conjugation with HCB induce lipid and DNA oxidative damage in C57BL/10ScSn mice. DNA oxidative damage may be important in the early events of hepatic carcinogenesis in experimental porphyria.
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PMID:Lipid and DNA oxidative damage in experimentally induced hepatic porphyria in C57BL/10ScSn mice. 1147

Recent studies suggest that moderate alcohol consumption is associated with a low risk of cancer, coronary heart disease, and other diseases. Most of these diseases are considered to be related to the action of reactive oxygen species (ROS) at certain stages of disease progression. However, considerable evidence exists indicating that ethanol generates ROS in vivo. Thus, the reduced risk of disease as a result of alcohol consumption seems to contradict evidence suggesting the induction of ROS by ethanol. In the present study, we investigated whether oxidative stress was induced in moderate alcohol drinkers. We measured the total urinary biopyrrins and 8-hydroxydeoxyguanosine (8-OHdG) levels as a systemic oxidative stress marker and an oxidative DNA damage marker, respectively. Serum uric acid was also measured as an alcohol-induced antioxidant. We compared total urinary biopyrrins and 8-OHdG levels among groups with different alcohol habits. The results showed that total biopyrrins levels increased with the amount of alcohol consumed, but that the level of 8-OHdG significantly decreased with the amount of alcohol consumed. The decrease in 8-OHdG levels seemed to be associated with increasing levels of uric acid. Judging from the increasing level of total biopyrrins, alcohol may induce ROS. ROS may then cause cell damage in liver, as suggested by the positive correlation between the total biopyrrins levels and the serum GOT, GPT, and gammaGTP levels. However, since ROS may be more effectively counteracted by uric acid in organs other than the liver, DNA damage may be suppressed rather than induced. Accordingly, moderate alcohol consumption seems to have the overall effect of reducing DNA damage, as shown by the decrease in urinary 8-OHdG levels observed in our study.
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PMID:Moderate alcohol consumption reduces urinary 8-hydroxydeoxyguanosine by inducing of uric acid. 1175 95

Heat shock preconditioning (HSPC) is a promising strategy for providing ischemic tolerance. The objective of this study is to investigate the effectiveness of HSPC in preventing oxidative damage of cellular proteins and DNA during ischemia-reperfusion of the liver. Male Wistar rats were divided into a heat shock group (group HS) and control (group C). Forty-eight hours prior to ischemia, rats in group HS received HSPC at 42 degrees C for 15 min. All rats received hepatic warm ischemia for 30min and subsequent reperfusion. The formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE) modified proteins in liver tissue, survival rate of the animals, and changes in biochemical and histological parameters were compared between groups. Heat shock protein 72 was produced only in group HS. The 7-day survival of rats was significantly better in group HS (10/10) than in group C (5/10) (p < 0.01). The serum release of alanine aminotransferase (n = 10, p < 0.01) and the concentration of adenosine triphosphate in liver tissue (n = 10, p < 0.01) 40min after reperfusion was significantly better in group HS than in group C. The formation of 8-OHdG in liver tissue measured by high-performance liquid chromatography was suppressed in group HS (p < 0.01). The production of HNE-modified proteins as determined by Western-blot analysis was also decreased in group HS. These results were also confirmed by immunohistochemical analysis. As determined by levels of 8-OHdG and HNE-modified proteins produced during ischemia-reperfusion of the liver, HSPC reduced the oxidative injury of cellular proteins and DNA in the liver tissue.
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PMID:Heat shock preconditioning reduces the formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal modified proteins in ischemia-reperfused liver of rats. 1199 85

Streptozotocin (STZ) has drawn attention as a potential source of oxidative stress, which induces genotoxicity. We investigated the effects of STZ on DNA damage in the liver and kidney, as well as the protective effects of antioxidants, by using the alkaline single-cell gel electrophoresis assay, and by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (8-OHdG) to dG. A single intraperitoneal injection of STZ (150 mg/kg) increased serum levels of glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and blood urea nitrogen (BUN), and also caused DNA damage in the liver and kidney, which recovered slowly with time. Antioxidants,(ascorbic acid, trolox and probucol) prevented the STZ-induced elevation of DNA damage in the liver and kidney and inhibited the increase in serum levels of AST, ALT and BUN. Thus ascorbic acid, trolox, and probucol protected the mice against STZ-induced DNA damage that might contribute to the development of hepatic or renal disease.
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PMID:DNA damage and the effect of antioxidants in streptozotocin-treated mice. 1206 20

The role of reactive oxygen species in liver fibrogenesis is not yet clarified. The aim of this study was to investigate oxidative-stress-related changes in cirrhotic rats. Cirrhosis was induced by bile duct ligation in Sprague-Dawley rats. Plasma malondialdehyde (MDA), hepatic 8-hydroxy-2'-deoxyguanosine (8-OHdG), hepatic mitochondrial respiratory functions and gene transcripts were measured at 2 and 4 weeks after surgery in bile-duct-ligated (BDL) and sham-operated-operated rats. The results showed progressive increases in the levels of plasma MDA, hepatic 8-OHdG and procollagen I and III mRNA expression, and progressive impairment of hepatic mitochondrial respiratory function in BDL rats at 2 and 4 weeks after ligation compared with sham-operated rats. Moreover, at 4 weeks after ligation, BDL rats exhibited reduced plasma glutathione and vitamin E levels, impaired hepatic mitochondrial electron transport enzyme activities and oxidative phosphorylation function. In addition, hepatic mRNA expression of transforming growth factor-beta1 was increased. Hepatomegaly, abnormal plasma alanine transaminase and aspartate transaminase levels, and portal hypertension were noted in BDL rats. Our results suggest that bile duct ligation in the rat induces mitochondrial dysfunction and biochemical and molecular changes related to oxidative stress in the liver.
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PMID:Oxidative-stress-related changes in the livers of bile-duct-ligated rats. 1259 53

Reactive oxygen species may be involved in the progression of chronic liver disease and the occurrence of hepatocellular carcinoma (HCC). To clarify whether clinicopathological findings in liver diseases are related to oxidative DNA damage, hepatic expression of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) was examined in 75 liver disease patients, which included 32 chronic hepatitis (CH), 13 liver cirrhosis (LC) and 30 HCC patients. The CH patients had higher 8-OHdG-positive hepatocytes than LC (P < 0.05). In CH and LC, the number of 8-OHdG-positive hepatocytes was correlated with alanine aminotransferase and asparate aminotransferase (P < 0.01 and P < 0.05, respectively). Of 30 HCC cases, 25 cases (83%) showed stronger immunoreactivity than non-cancerous counterparts. The patients with poorly differentiated HCC had a larger tumor size and higher levels of AFP, and exhibited higher labeling indices of PCNA-, TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated HCC. Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic liver disease and determination of 8-OHdG is useful in assessing high-grade malignancy in HCC.
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PMID:Expression of 8-hydroxy-2'-deoxyguanosine in chronic liver disease and hepatocellular carcinoma. 1470 94


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