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)

Murine hepatic cytochrome P450 2A5 (CYP2A5) is uniquely induced by a variety of agents that cause liver injury and inflammation, conditions that are typically associated with downregulation of P450s. We hypothesized that induction of CYP2A5 occurs in response to hepatocellular damage resulting in endoplasmic reticulum (ER) stress. Treatment of mice in vivo and mouse hepatocytes in primary culture with the CYP2A5 inducer pyrazole resulted in overexpression of the ER stress biomarker glucose-regulated protein (GRP) 78. Treatment of primary hepatocytes with ER stress activators thapsigargin, tunicamycin, and trans-4,5-dihydroxy-1,2-dithiane (DTT(ox)) and the calcium ionophore A23187 (calcimycin) resulted in elevated GRP78 mRNA levels; however, only the reducing agent DTT(ox) induced levels of CYP2A5 mRNA, protein, and coumarin 7-hydroxylase activity. To test the hypothesis that CYP2A5 induction is due to liver injury resulting from altered cellular redox status, we demonstrated that CYP2A5 induction, elevated serum alanine aminotransferase, and oxidative protein damage occur concurrently in pyrazole-treated mice. Pyrazole also induced the expression of cytosolic alpha and mu class glutathione S-transferase expression both in vivo and in primary mouse hepatocytes. Moreover, treatment of hepatocytes with the redox cycling quinone menadione resulted in overexpression of CYP2A5 and GSTM1 mRNA. Finally, pretreatment of hepatocytes with the antioxidants N-acetylcysteine and vitamin E attenuated pyrazole-mediated increases in CYP2A5 mRNA levels. These findings clearly indicate that induction of mouse hepatic CYP2A5 during liver injury occurs via a novel mechanism involving ER stress due to altered cellular redox status.
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PMID:Endoplasmic reticulum stress due to altered cellular redox status positively regulates murine hepatic CYP2A5 expression. 1461 Feb 26

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

Adult eels (Anguilla anguilla L.) were exposed for 8, 16, 24, and 72 h to 0, 0.1, 0.3, 0.9, and 2.7 microM abietic acid (AA). Genotoxicity was measured as erythrocytic nuclear abnormalities (ENA), as well as DNA strand breaks in blood and liver. Liver cytochrome P450 (P450) content, liver ethoxyresorufin O-deethylase (EROD), and glutathione S-transferase (GST) activities were determined as biotransformation biomarkers. Liver alanine transaminase (ALT) activity was also measured as an indication of tissue damage. Low AA concentrations, such as 0.1 and 0.3 microM, result in a delayed induction of A. anguilla L. liver EROD activity, whereas the higher AA concentration (2.7 microM AA) also has a delayed effect probably as a consequence of liver tissue high inhibitory concentration. The current eel liver GST activity results demonstrate that only low AA concentrations promote liver increases in GST, whereas high AA concentrations, such as 0.9 and 2.7 microM, do not alter it. The results concerning eel liver ALT activity indicate that significant liver damage is induced by high AA concentrations, such as 2.7 and 0.9 microM. The eel ENA result analysis reveals that AA is a weak ENA inducer in A. anguilla L. Blood DNA integrity results suggest that low AA concentrations promote late decreases in blood DNA integrity; nevertheless, high AA concentrations are early blood genotoxic inducers compared with low AA doses. According to the present research results with respect to eel liver DNA damage, all of the AA exposure concentrations decreased liver DNA integrity.
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PMID:Anguilla anguilla L. genotoxic and liver biotransformation responses to abietic acid exposure. 1515 74

Role of alpha-tocopherol (vitamin E), beta-carotene and/or their combination as antioxidants against the toxicity of fenvalerate on blood hematology, free radicals, biochemical parameters, and semen quality were studied in male rats. Fenvalerate (20 mg/kg BW), vitamin E (100 mg/kg BW), beta-carotene (10 mg/kg BW), and vitamin E plus beta-carotene (100 + 10 mg/kg BW, respectively) were given alone or in combination with fenvalerate. The tested doses were given to rats every other day for 30 days. Results obtained showed that fenvalerate significantly (P < 0.05) induced free radicals in plasma and brain and insignificantly in liver and testes. While, vitamin E, beta-carotene alone and/or in combination decreased the levels of free radicals in plasma, liver, testes, and brain. The activities of glutathione S-transferase (liver), alkaline phosphatase (plasma and liver), aspartate aminotransferase (plasma, liver, and testes) and alanine aminotransferase (plasma and liver) were significantly (P < 0.05) increased due to fenvalerate administration. The activity of acetylcholinesterase was significantly (P < 0.05) decreased in brain and plasma, while plasma glucose, urea, creatinine, and bilirubin concentrations were significantly (P < 0.05) increased in rats treated with fenvalerate. Also, results showed a significant (P < 0.05) alterations in plasma proteins, hematological parameters, body weight, and relative weights of organs. Sperm concentration and motility (%) were significantly (P < 0.05) decreased, while dead and abnormal sperm increased in rats exposed to fenvalerate. Vitamin E, beta-carotene alone and/or in combination did not cause any changes in the investigated parameters, but improved semen quality and minimized the toxic effect of fenvalerate. The obtained results demonstrated the beneficial influences of vitamin E, beta-carotene alone and/or in combination in reducing the harmful effects of fenvalerate.
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PMID:Role of alpha-tocopherol and beta-carotene in ameliorating the fenvalerate-induced changes in oxidative stress, hemato-biochemical parameters, and semen quality of male rats. 1518 33

Cadmium is a well-known human carcinogen and a potent nephrotoxin. Lipid peroxidation is involved in cadmium-related toxicity. Vitamin E and beta-carotene are effective antioxidants and free radical scavengers. Therefore, the present study was carried out to investigate the potential protective effects of vitamin E and beta-carotene alone or in combination against cadmium (Cd) toxicity. Cadmium chloride (CdCl2, 5 mg/kg BW, 1/15 LD50), vitamin E (100 mg/kg BW), beta-carotene (10 mg/kg BW), and vitamin E with beta-carotene (100 + 10 mg/kg BW, respectively) were orally administered by gavage alone or in combination. The tested doses were given to rats every other day (15 times). Results obtained showed that CdCl2 significantly (P < 0.05) induced free radicals in plasma, liver and brain. The activities of glutathione S-transferase (GST) (plasma and liver), alkaline phosphatase (AlP) (plasma and liver), aspartate aminotransferase (AST), alanine aminotransferase (ALT) (liver) and acetylcholinesterase (AChE) (plasma and brain) were significantly (P < 0.05) decreased due to CdCl2 administration, whereas, the activities of AST and ALT were increased in plasma. Treatment with CdCl2 caused a significant (P < 0.05) increase in glucose, urea, creatinine and bilirubin in plasma. On the other hand, results showed that CdCl2 significantly (P < 0.05) decreased plasma total protein (TP), albumin (A), blood hemoglobin (Hb), total erythrocytic count (TEC) and packed cell volume (PCV), while total leukocyte count (TLC) increased. Treatment with CdCl2 caused a significant (P < 0.05) decrease in sperm concentration, motility (%), weight of testes and epididymis, and increase in dead and abnormal sperm. Results demonstrated the beneficial influences of vitamin E, -carotene alone and/or in combination in reducing the harmful effects of CdCl2.
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PMID:Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and beta-carotene. 1530 3

Aluminium has the potential to be neurotoxic in humans and animals, and is present in many manufactured foods and medicines and is also added to drinking water for purification purposes. Therefore, the present study was carried out to investigate (1) the alterations in biochemical parameters, free radicals and enzyme activities induced by aluminium chloride (AlCl3) in plasma and different tissues of male rats, and (2) the role of vitamin E (VE) and selenium in alleviating the negative effects of aluminium. VE plays an important role as an antioxidant and is consequently expected to protect tissues from damage caused by reactive oxygen metabolites. Selenium is also generally recognized to be a trace mineral of great importance for human health, protecting the cells from the harmful effects of free radicals. Seven rats per group were assigned to one of six treatment groups: 0 mg VE, 0 mg Se and 0 mg AlCl3/kg body weight (BW) (control); 100 mg VE/kg BW; 200 microg Se kg BW; 34 mg AlCl3/kg BW (1/25 LD50); 34 mg AlCl3 plus 100 mg VE/kg BW; 34 mg AlCl3 plus 200 microg Se/kg BW. Rats were orally administered their respective doses every other day for 30 days. Evaluations were made for lipid peroxidation, enzyme activities and biochemical parameters. Results obtained showed that AlCl3 significantly (p<0.05) induced free radicals (thiobarbituric acid-reactive substances) and decreased the activity of glutathione S-transferase (GST) and the levels of sulphydryl groups (SH groups) in rat plasma, liver, brain, testes and kidney. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acid phosphatase, and phosphorylase activities were significantly decreased in liver and testes due to AlCl3 administration, while the activities of these enzymes were significantly increased in plasma. In addition, plasma, liver, testes and brain lactate dehydrogenase activities were significantly increased. On the contrary, the activity of acetylcholinesterase was significantly decreased in brain and plasma. Al treatment caused a significant decrease in plasma total protein (TP), albumin and total lipids (TL), and increased the concentrations of glucose, urea, creatinine, bilirubin and cholesterol. VE or Se alone significantly decreased the levels of free radicals, TL, cholesterol, urea and bilirubin, and increased the activity of GST, and SH groups, TP and albumin, while the rest of the tested parameters were not affected. VE or Se in combination with Al partially or totally alleviated its toxic effects on the studied parameters. In conclusion, VE and Se have beneficial effects and could be able to antagonize Al toxicity.
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PMID:Antioxidant effect of vitamin E and selenium on lipid peroxidation, enzyme activities and biochemical parameters in rats exposed to aluminium. 1548 71

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.
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PMID:Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum. 1556 72

The present study was carried out to investigate the effects of onion (Allium cepa Linn) and garlic (Allium sativum Linn) juices on biochemical parameters, enzyme activities and lipid peroxidation in alloxan-induced diabetic rats. Alloxan was administered as a single dose (120 mg/kg BW) to induce diabetes. A dose of 1 ml of either onion or garlic juices/100 g body weight (equivalent to 0.4 g/100 g BW) was orally administered daily to alloxan-diabetic rats for four weeks. The levels of glucose, urea, creatinine and bilirubin were significantly (p<0.05) increased in plasma of alloxan-diabetic rats compared to the control group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline and acid phosphatases (AlP, AcP) activities were significantly (p<0.05) increased in plasma and testes of alloxan-diabetic rats, while these activities were decreased in liver compared with the control group. Brain LDH was significantly (p<0.05) increased. The concentration of thiobarbituric acid reactive substances and the activity of glutathione S-transferase in plasma, liver, testes, brain, and kidney were increased in alloxan-diabetic rats. Treatment of the diabetic rats with repeated doses of either garlic or onion juices could restore the changes of the above parameters to their normal levels. The present results showed that garlic and onion juices exerted antioxidant and antihyperglycemic effects and consequently may alleviate liver and renal damage caused by alloxan-induced diabetes.
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PMID:Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats. 1558 96

The objective of this study was to determine the effect of either 2.5 mg/kg Body Weight or 5 mg/kg Body Weight (BW) doses of isoflavones on semen quality, testosterone levels, lipid peroxidation and semen biochemistry of male New Zealand White rabbits. Animals were given both 2.5 mg/kg BW and 5 mg/kg BW doses of isoflavones. The tested doses were given to rabbits orally every other day for 13 weeks. Treatment with isoflavones caused an increase (p < 0.05) in libido (by decreasing the reaction time), sperm concentration, sperm motility (%), total motile sperm per ejaculate (TMS), packed sperm volume (PSV), total functional sperm fraction (TFSF), total sperm output, initial fructose concentration and normal sperm, while dead sperm was reduced compared to control animals. On the other hand, ejaculate volume, initial hydrogen ion concentration (pH) and plasma testosterone levels did not change in treated animals with both doses of isoflavones as compared to control. Concentrations of thiobarbituric acid-reactive substances (TBARS), total lipids, and low density lipoprotein were significantly (p < 0.05) reduced in seminal plasma of rabbits treated with either 2.5 mg/kg BW or 5 mg/kg BW doses of isoflavones. While, the activities of glutathione S-transferase (GST), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), acid phosphatase (AcP), and alkaline phosphatase (AlP) were significantly (p < 0.05) increased in seminal plasma of treated animals. Also, total cholesterol, percentage cholesterol (out of total lipids), and high density lipoprotein were significantly (p < 0.05) increased, while triglyceride did not change in seminal plasma of treated animals. Supplementation at either level of isoflavones did not cause changes in live body weight (LBW), dry matter intake (DMI), and relative weights of testes and epididymis. The present results showed that either 2.5 mg/kg BW or 5 mg/kg BW doses of isoflavones caused an improvement of some semen characteristics and did not have negative effects on male fertility.
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PMID:Effect of isoflavones on reproductive performance, testosterone levels, lipid peroxidation, and seminal plasma biochemistry of male rabbits. 1562 89

We previously reported that, as compared with selenite, nano red elemental selenium (Nano-Se) had lower acute toxicity in mice and similar bioavailability in terms of up-regulating seleno-enzymes. The short-term toxicity of both selenite and Nano-Se in mice was further compared in this study. At an oral dose of 6 mg/kg bw per day administered for consecutive 12 days, selenite and Nano-Se completely and partially suppressed mice growth respectively. Abnormal liver function was more pronounced with selenite treatment than Nano-Se as indicated by the increase of both alanine aminotransferase and aspartate aminotransferase in serum. Selenite inhibited liver catalase and superoxide dismutase activities, whereas, Nano-Se did not affect these two antioxidant enzymes. Selenite increased the malondialdehyde content of liver, but Nano-Se decreased it. Both Se forms had similar effects on depletion of reduced glutathione and up-regulated glutathione peroxidase. Nano-Se was more potent than selenite in the induction of glutathione S-transferase. At oral doses of 2 or 4 mg/kg bw per day for consecutive 15 days, selenite was more active than Nano-Se in supressing growth, deleting reduced glutathione, and inhibiting superoxide dismutase activities. Taken together, these results indicate that over a short-term, a high-dose of selenite caused more pronounced oxidative stress, greater liver injury, and prominent retardation of growth as compared to Nano-Se.
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PMID:Comparison of short-term toxicity between Nano-Se and selenite in mice. 1562 May 74


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