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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mercury is a widespread metal in the environment and consequently large populations are currently exposed to low levels of mercury. Endotoxin, a component of the Gram-negative bacteria, promotes inflammatory responses. We recently reported that mercury modulates the production of nitric oxide and various inflammatory cytokines induced by endotoxin in a macrophage cell line (Nitric Oxide 2002, 7:67). The present study was designed to determine the impact of mercury on endotoxin-induced inflammatory cytokine expression and corresponding signal transduction in mouse liver. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercury in drinking water for 14 days and at the end of the treatment period lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 hr prior to euthanasia. The doses of mercury and LPS did not cause hepatotoxicity as indicated by unaltered circulating alanine aminotransferase and aspartate aminotransferase levels. Mercury decreased liver glutathione (GSH) and with LPS additively decreased GSH. Mercury activated p38 mitogen-activated protein kinase (MAPK) and additively increased LPS-induced p38 MAPK phosphorylation. In contrast, mercury alone had no effect on activation of extracellular signal-regulated kinase (ERK) but inhibited LPS-induced ERK activation. Mercury increased the expression of tumor necrosis factor alpha (TNFalpha) and further potentiated LPS-induced TNFalpha expression. Mercury did not affect LPS-induced interleukin (IL)-1beta expression but decreased LPS-induced IL-6 expression. Results indicated that low levels of mercury augment LPS-induced TNFalpha expression by altering GSH and p38 MAPK. Mercury modulates LPS-induced p38 and ERK activation and downstream TNFalpha and IL-6 expression in mouse liver.
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PMID:Mercury alters endotoxin-induced inflammatory cytokine expression in liver: differential roles of p38 and extracellular signal-regulated mitogen-activated protein kinases. 1580 65

Metallothionein (MT) is a small sulfydryl-rich protein that binds to and is inducible by heavy metals such as mercury, cadmium, zinc, and copper. However, little is known about the induction of MT by trivalent metals except for bismuth. In this study, we examined the induction of MT synthesis by cerium, a trivalent lanthanoid metal. Administration of cerium chloride (CeCl3) to mice resulted in accumulation of cerium and induction of MT in the liver in a dose-dependent manner. Distribution profiles of metals in the soluble fraction of the liver of CeCl3-treated mice analyzed by high performance liquid chromatography/inductively coupled argon plasma-mass spectrometry (HPLC/ICP-MS) demonstrated that the metal bound to MT-I and MT-II was zinc, but not cerium. Administration of CeCl3 caused increases in the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the levels of serum amyloid A (SAA), an acute phase protein. Among inflammatory cytokines examined, interleukin 6 (IL-6) exhibited a marked increase in the serum at 3 h after the CeCl3 administration. In order to evaluate the involvement of IL-6 in the induction of MT by cerium, we examined MT induction by CeCl3 in IL-6 null mice. Both the induction of hepatic MT and the increases in SAA levels were markedly suppressed in IL-6 null mice. These results suggest that IL-6 plays an important role in the induction of hepatic MT by cerium.
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PMID:Induction of hepatic metallothionein by trivalent cerium: role of interleukin 6. 1620 35

In recent years, high concentrations of mercury have been found in wading birds in Florida, USA. Great egret (Ardea alba) chicks (2 weeks old) were dosed orally daily with the equivalent of 0, 0.5, or 5 microg/g Hg as methylmercury chloride in the diet for up to 12 weeks. Weakness of the legs or paralysis occurred in all high-dosed birds. Geometric mean blood Hg concentrations were 0.17, 10.3, and 78.5 microg/g (wet wt), respectively. Mercury concentrations for organs (microg/g wet wt), including brain (0.22, 3.4, and 35, respectively), liver (0.34, 15.1, 138, respectively), and kidney (0.28, 8.1, and 120, respectively), increased in a dose-dependent manner. Total glutathione (GSH) peroxidase activity was significantly lower in the plasma, brain, liver, and kidney of the high-dosed group. Plasma aspartate aminotransferase activity increased with mercury treatment, whereas lactate dehydrogenase activity decreased. Four other plasma chemistries were decreased significantly in the high-dosed group and included uric acid, total protein, albumin, and inorganic phosphorus. Lipid peroxidation increased in liver (low and high dose) and brain (high dose). Tissue changes in concentrations of reduced thiols included decreased total thiols and protein-bound thiols in liver, decreased protein-bound thiols in kidney, and increased GSH in kidney and brain. Activities of GSH S-transferase and oxidized glutathione reductase increased in liver. In kidney, GSH S-transferase and glucose-6-phosphate dehydrogenase activities increased with mercury dose. These findings, including apparent compensatory changes, are compared to other Hg studies where oxidative stress was reported in egrets, herons, and diving ducks in the field and mallards in the laboratory.
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PMID:Subchronic effects of methylmercury on plasma and organ biochemistries in great egret nestlings. 1644 88

Acute effects of mercury on mouse blood, kidneys, and liver were evaluated. Mice received a single dose of mercuric chloride (HgCl2, 4.6 mg/kg, subcutaneously) for three consecutive days. We investigated the possible beneficial effects of antioxidant therapy (N-acetylcysteine (NAC) and diphenyl diselenide (PhSe)2) compared with the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), an effective chelating agent in HgCl2 exposure in mice. We also verified whether metallothionein (MT) induction might be involved in a possible mechanism of protection against HgCl2 poisoning and whether different treatments would modify MT levels and other toxicological parameters. The results demonstrated that HgCl2 exposure significantly inhibited delta-aminolevulinate dehydratase (delta-ALA-D) activity in liver and only DMPS treatment prevented the inhibitory effect. Mercuric chloride caused an increase in renal non-protein thiol groups (NPSH) and none of the treatments modified renal NPSH levels. Urea concentration was increased after HgCl2 exposure. NAC plus (PhSe)2 was partially effective in protecting against the effects of mercury. DMPS and (PhSe)2 were effective in restoring the increment in urea concentration caused by mercury. Thiobarbituric acid-reactive substances (TBARS), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities and ascorbic acid levels were not modified after mercury exposure. Mercuric chloride poisoning caused an increase in hepatic and renal MT levels and antioxidant treatments did not modify this parameter. Our data indicated a lack of therapeutic effect of the antioxidants tested.
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PMID:Antioxidants and metallothionein levels in mercury-treated mice. 1696 87

Mercury(II) is a highly toxic metal which induces oxidative stress in the body. In this study we aimed to investigate the possible protective effect of Ginkgo biloba (EGb), an antioxidant agent, against experimental mercury toxicity in rat model. Following a single dose of 5mg/kg mercuric chloride (HgCl(2); Hg group) either saline or EGb (150mg/kg) was administered for 5days. After decapitation of the rats trunk blood was obtained and the tissue samples from the brain, lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Formation of reactive oxygen species in the tissue samples was monitored by chemiluminescence (CL) technique. BUN, creatinin, ALT, and AST levels and tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) activity were assayed in serum samples. The results revealed that HgCl(2) induced oxidative damage caused significant decrease in GSH level, significant increase in MDA level, MPO activity and collagen content of the tissues. Treatment of rats with EGb significantly increased the GSH level and decreased the MDA level, MPO activity, and collagen contents. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the Hg group as compared to control group. On the other hand, EGb treatment reversed all these biochemical indices. Our results implicate that mercury-induced oxidative damage in brain, lung, liver, and kidney tissues protected by G. biloba extract, with its antioxidant effects.
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PMID:Ginkgo biloba extract protects against mercury(II)-induced oxidative tissue damage in rats. 1726 89

In the current study, we examined whether subchronic exposure via drinking water to low doses of a mixture of metals (arsenic, cadmium, lead, mercury, chromium, manganese, iron, and nickel), found as contaminants in various water sources of India, and to concentrations equivalent to WHO maximum permissible limits (MPL) in drinking water for individual metals, can alter systemic physiology of male rats. Data on water contamination with metals in India were collected from the literature and metals were selected on the basis of their frequency of occurrence and contamination level above MPL. Male Wistar rats were exposed to the mixture at 0, 1, 10, and 100 times the mode concentrations (the most frequently occurring concentration) of the individual metals via drinking water for 90 days. One more group of rats was exposed to the mixture at a concentration equivalent to the MPL (WHO) in drinking water for individual metals. Toxic potential of the mixture was evaluated by assessing general toxicological end points, serum chemistry and histopathology of vital organs. The mixture decreased body weight and water consumption and increased weights of brain, liver, and kidneys with 10x and 100x doses. After 30 days of exposure, no appreciable changes were found in any blood clinical markers. After 60 days, only the 100x dose, while after 90 days both 10x and 100x doses increased activities of aspartate aminotransferase and alkaline phosphatase and levels of urea nitrogen and creatinine and decreased total protein and albumin levels, but alanine aminotransferase activity and glucose level were not affected. At 10x and 100x exposure levels, qualitatively similar, but dose-dependent vascular, degenerative, and necrotic changes were observed in brain, liver, and kidney. The results indicate that subchronic exposure to the metal mixture affected general health of male rats by altering the functional and structural integrity of kidney, liver, and brain at 10 and 100 times the mode concentrations of the individual metals in Indian water sources, but exposure at mode concentrations of contemporary water contamination levels or at concentrations equivalent to the MPL for individual metals in drinking water may not cause any health hazards in male rats.
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PMID:Effects of subchronic exposure via drinking water to a mixture of eight water-contaminating metals: a biochemical and histopathological study in male rats. 1788 70

Efficacy of thiol chelators viz. N-acetyl cysteine and D-penicillamine (NAC and DPA) along with nutritional supplements viz. zinc acetate, sodium selenite and magnesium sulphate (Zn, Se and Mg) in the treatment of mercury intoxication was investigated in rats. This is of particular interest since high bonding affinity between mercuric ion and the thiol group exits. The mutual antagonism of mercury and selenium is one of the strongest examples of the interaction in the trace element field. Adult rats of Sprague-Dawley strain were administered a bolus dose of dimethyl mercury (10 mg/kg) orally. A significant rise in the aspartate aminotransferase, alanine aminotransferase, serum alkaline phosphatase, lactate dehydrogenase, gamma glutamyltranspeptidase, bilirubin and creatinine were observed. Single mercury exposure also resulted in a significant increase in lipid peroxides with a concomitant decrease in reduced glutathione level in liver, kidney and brain. A decrease in the enzymatic activities of acetyl cholinesterase in different regions of the brain was observed. These parameters were restored considerably with chelating agents along with nutritional supplementation, but NAC+Se and DPA+Mg offered significant protection in comparison with other combinations.
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PMID:Effect of monothiol along with antioxidant against mercury-induced oxidative stress in rat. 1825 9

The purpose of this study was to examine concentrations of selected heavy metals in the liver and kidney of brown hares (Lepus europaeus). In addition, correlations between heavy metals and biochemical parameters in blood plasma were determined. The average concentrations of heavy metals (mmol/L) +/- SD were as follows: liver: Pb 0.221 +/- 0.189, Cd 0.160 +/- 0.140, Hg 0.021 +/- 0.030, kidney: Pb 0.115 +/- 0.125, Cd 1.570 +/- 1.103, Hg 0.030 +/- 0.053. The average concentrations of biochemical parameters in the blood plasma were as follows: Ca 3.16 mmol/L, P 2.19 mmol/L, Mg 1.40 mmol/L, Na 148.71 mmol/L, K 8.12 mmol/L, glucose 6.56 mmol/L, total proteins 56.49 g/L, urea 5.00 mmol/L, total lipids 1.40 g/L, bilirubin 3.97 micro mol/L, cholesterol 1.53 mmol/L, aspartate aminotransferase (AST) 6.06 micro kat/L and alanine aminotransferase (ALT) 1.94 micro kat/L. Average levels of hormones (ng/mL) were as follows: testosterone 2.94, androstendiol 0.13, estradiol 501.59, progesterone 6.63, oxytocin 328.60. Tissue analysis showed an accumulation of lead, cadmium and mercury in the liver and kidney of brown hares. There were no significant correlations between levels of heavy metals in liver, kidney, and biochemical parameters.
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PMID:Environmental levels of cadmium, lead and mercury in brown hares and their relation to blood metabolic parameters. 1839 73

An attempt has been made to study the influence of taurine on mercury intoxicated rats. The animals were treated with sublethal dose of mercuric chloride (2 mg/kg body wt.) for 30 days. During the mercury treatment, the level ofAspartate transaminase(AST), Alanine transaminase (ALT) and Alkaline phosphatase(ALP) in serum and lipid peroxidation (LPO) in liver tissue significantly increased whereas Glutathione (GSH), Glutathione peroxidase(GPx), Catalase (CAT) and Superoxide dismutase (SOD) were simultaneously decreased in the liver tissue. Present results indicate that the liver tissue was completely damaged, after mercury treatment. In another group of animals, taurine (5 mg/kg body wt.) was administrated for another 15 days. Taurine administration was observed to improve the liver function in mercury intoxicated animal as indicated by the decline in increased levels of AST, ALT and ALP in serum and LPO content in liver tissue. The decreased level of antioxidant system (GSH, GPx, CATand SOD) has been promoted Results suggested that taurine played a vital role in reducing the mercury toxicity in intoxicated animals.
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PMID:Hepatoprotective effects of taurine against mercury induced toxicity in rats. 1840 8

The present study was designed to compare the protective effect of selenium and garlic against liver and kidney damage induced by (ip) injection of 0.5 mg/kg mercury chloride (HgCl(2)) in rats. Thirty-six Sprague-Dawley rats were used in the present experiment and divided into six groups: one group was orally given (1 ml) saline and served as a control group; two groups of rats were given either selenium (0.1 mg/kg) or garlic (63 mg/kg) alone, once daily an oral dose for 30 successive days; other two groups of rats were given either selenium or garlic alone, once daily a dose for 15 successive days prior to HgCl(2) injection and on the next 15 successive days simultaneously with HgCl(2) injection; and the last group of rats was injected ip with HgCl(2) for 15 days and at the end of the experiment (which lasted 30 days), blood samples for the biochemical analysis were obtained from all rats after being lightly anesthetized with ether, and specimens of kidney and liver were removed and prepared for histochemical study. Computer image analysis was applied to liver and kidney tissues to evaluate the DNA density and DNA ploidy pattern in different groups. The results revealed that the rats injected with HgCl(2) showed a significant increase in levels of blood urea nitrogen (BUN), serum creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) by 29.3%, 62.5%, 29.46% and 30.61%, respectively, while alkaline phosphatase (ALP) showed a significant decrease by 22.6% as compared with saline control group. Rats that were given selenium in combination with the HgCl(2) injection showed a significant decrease in BUN, Serum creatinine, ALT and AST levels, while ALP was significantly increased as compared with HgCl(2) group. Also rats that were given garlic in combination with HgCl(2) injection showed a significant decrease in BUN, Serum creatinine, ALT and AST levels, although serum ALP level showed an increase as compared to HgCl(2) group. Rats that had been orally administered selenium or garlic alone did not show any significant changes in the serum level of BUN, Serum creatinine, ALT and AST but there was a significant decrease in ALP level as compared with saline control group. The cytometric results revealed that injection of HgCl(2) induced an increase in the DNA density in kidney tissues with an increase in aneuploid cells and decrease in diploid cells. However, DNA density decreased in liver tissues with mild decrease in diploid cells and little percentage of aneuploid cells. We can conclude that oral administration of either selenium or garlic produces a significant protection against liver and kidney damage induced by the HgCl(2) injection, but garlic appears to be more protective.
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PMID:Comparative evaluation of the protective effect of selenium and garlic against liver and kidney damage induced by mercury chloride in the rats. 1844 81


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