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)

Neutrophil elastase (NE) is thought to be the most important protease which damages the cystic fibrosis (CF) lung. Attempts have been made to suppress this activity using the plasma-derived inhibitor, alpha(1)-antitrypsin (AAT). In this pilot study, the safety and efficacy of inhaled recombinant human AAT (rAAT) as a treatment for CF were investigated. Thirty-nine patients participated in a prospective, double-blinded, randomized, placebo-controlled phase II trial to examine the effect of rAAT (500, 250, and 125 mg) on sputum NE activity. Sputum myeloperoxidase (MPO), interleukin-8, tumor necrosis factor receptors, sputum and plasma NE/AAT complexes, and safety parameters were also measured. Subjects were randomized to receive nebulized treatment once a day for 4 weeks, followed by 2-4 weeks with no study treatment, and then a 2-week rechallenge phase. Trends toward a reduction in NE activity were observed in patients treated with 500 mg and 250 mg of rAAT compared to placebo. Sputum NE/AAT complex and MPO levels were lower on rAAT compared to placebo. No major adverse events and, in particular, no allergic reactions to rAAT were observed. Although significant differences between rAAT and placebo for sputum NE activity were not observed, some improvements were found for secondary efficacy variables. This study demonstrated that nebulized rAAT is safe and well-tolerated, but has a limited effect on NE activity and other markers of inflammation.
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PMID:Safety and efficacy of recombinant alpha(1)-antitrypsin therapy in cystic fibrosis. 1637 52

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

Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs; the damage is believed to be due to ischemia/reperfusion (I/R) injury. In this study, we examined the role of oxidative damage in PU and the beneficial effect of treatment with the antioxidant melatonin. PU were induced by applying magnets over steel plates that were implanted under the skin of rats; this compressed the skin and caused ischemia. Within a 12-hr period, rats were subjected to five cycles of I/R (2 and 0.5 hr respectively), followed by an additional 12 hr of ischemia (to simulate the period at sleep at night). This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, melatonin (5 mg per rat) was either applied locally as an ointment on skin, or administered i.p. (10 mg/kg). At the end of the experimental period, blood and tissue (skin, liver, kidney, lung, stomach, and ileum) samples were taken for determination of biochemical parameters and for histological evaluation. Local treatment with melatonin inhibited the increase in malondialdehyde levels; an index of lipid peroxidation, myeloperoxidase activity; an indicator of tissue neutrophil infiltration, and the decrease in glutathione; a key antioxidant, in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and collagen levels in animals with PU were prevented by melatonin treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU rats. Tissue injury was decreased especially in the locally treated group. Findings of the present study suggest that local and/or systemic melatonin treatment may prove beneficial in the treatment of PU.
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PMID:Melatonin protects against pressure ulcer-induced oxidative injury of the skin and remote organs in rats. 1649 65

This study was designed to investigate the effect of Ligustrazine on burn-induced liver injury as well as the activation of nuclear factor kappaB (NF-kappaB) in severely burned rats. Sprague-Dawley rats were divided into three groups: (1) sham group, rats who underwent sham burn; (2) control group, rats given third-degree burns over 30% total body surface area (TBSA) and lactated Ringer solution for resuscitation; (3) Ligustrazine group, rats given burn and lactated Ringer's solution with Ligustrazine inside for resuscitation. Liver injury was assessed at 24 h post-burn by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as liver wet/dry weight ratio. Liver myeloperoxidase (MPO) activity was also analyzed. Hepatic NF-kappaB activity was examined by electrophoretic mobility shift assay (EMSA). Burn results in hepatic dysfunction and increased hepatic NF-kappaB activity, elevated liver wet/dry ratio and hepatic MPO activity. Ligustrazine inhibited these changes and alleviated burn-mediated hepatic dysfunction. The data indicated that Ligustrazine has a protective effect on burn-induced liver injury and possible mechanism may be attributed to its inhibitory action on the activation of NF-kappaB following burn trauma.
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PMID:Effect of Ligustrazine on liver injury after burn trauma. 1652 67

Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs. In this study we investigated the role of oxidative damage in PUs and the probable beneficial effect of beta-glucan treatment against this damage. beta-glucan is known to have immunomodulatory effects. Experiments were carried on Wistar albino rats. PU was induced by applying magnets over steel plates that were implanted under the skin, to compress the skin and cause ischemia where removing the magnets cause reperfusion of the tissue. Within the first 12 h, rats were subjected to 5 cycles of ischemia/reperfusion (I/R), followed by 12 h ischemia. This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, beta-glucan was either applied locally (25 mg/kg) as an ointment on skin, or administered orally (50 mg/kg) as a gavage. At the end of the experimental periods, tissue samples (skin, liver, kidney, lung, stomach, and ileum) were taken for the measurement of malondialdehyde (MDA)--an index of lipid peroxidation--and glutathione (GSH)--a key antioxidant--levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase activity, while collagen contents were measured for the evaluation of tissue fibrosis. Skin tissues were also examined microscopically. Liver and kidney functions were assayed in serum samples. Local treatment with beta-glucan inhibited the increase in MDA and MPO levels and the decrease in GSH in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, BUN, ALT, AST, LDH and collagen levels in PU group were prevented by beta-glucan treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU group. Tissue injury was decreased especially in the locally treated group. Thus, supplementing geriatric and neurologically impaired patients with adjuvant therapy of beta-glucan may have some benefits for successful therapy and improving quality of life.
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PMID:Pressure ulcer-induced oxidative organ injury is ameliorated by beta-glucan treatment in rats. 1654 2

The aim of this study was to assess the antioxidant and antifibrotic effects of chronic administration of 2-mercaptoethane sulfonate (MESNA) on oxidative liver damage and fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission (BDL). MESNA (150mg/kg, i.p.) or saline was administered for 28 days. At the end of the experiment, rats were killed by decapitation. Serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were determined to assess liver function. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehidrogenase (LDH) were also assayed in serum samples. Liver tissues were taken for determination of the free radicals, hepatic malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker was also determined. Serum AST, ALT, LDH and TNF-alpha levels were elevated in the BDL group as compared to control group, while this increase was significantly decreased by MESNA treatment. BDL caused a significant (p<0.05-0.001) decrease in GSH levels while MDA levels and MPO activity were increased in the liver tissue. These changes were reversed by MESNA treatment. Collagen contents of the liver tissue was increased by BDL (p<0.001), and reversed back to the control levels with MESNA. Since MESNA administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic functions, it seems likely that MESNA with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.
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PMID:2-Mercaptoethane sulfonate (MESNA) protects against biliary obstruction-induced oxidative damage in rats. 1658 14

This investigation elucidates the role of free radicals in acetaminophen (AA)-induced toxicity and the possible protection by resveratrol (RVT). BALB-c mice were injected with a single dose of 900mg/kg AA to induce toxicity, while RVT administred in a dose of 30mg/kg i.p. following AA. Mice were sacrificed 4h after AA injection to determine serum ALT, AST and tumor necrosis factor-alpha (TNF-alpha) levels in blood, and glutathione (GSH), malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver tissues. Formation of reactive oxygen species in hepatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probe. ALT, AST levels and TNF-alpha were increased significantly after AA treatment, and reduced with RVT. AA caused a significant decrease in GSH levels while MDA levels and MPO activity were increased in liver tissues. On the other hand when RVT administered following AA, depletion of GSH and accumulation of MDA and neutrophil infiltration were reversed back to control. Furthermore increased luminol and lucigenin CL levels in the AA group reduced by RVT treatment. Our results implicate that AA causes oxidative damage in hepatic tissues and RVT, by its potent antioxidant effects protects the liver tissue. These data suggest that RVT may be of therapeutic use in preventing hepatic oxidative injury due to AA toxicity.
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PMID:Protective effects of resveratrol against acetaminophen-induced toxicity in mice. 1659 88

The aim of the present study was to evaluate pharmacological and toxicological properties of 1-buthyltelurenyl-2-methylthioheptene (compound 1). In vitro, compound 1 at 1 microM was effective in reducing lipid peroxidation induced by Fe/EDTA. Compound 1 presented neither thiol peroxidase nor thiol oxidase activity and did not change delta-ALA-D (delta-aminolevulinate dehydratase) activity (10-400 microM). Calculated LD(50) of compound 1, administered by oral route, was 65.1 micromol/kg. Rats treated with compound 1 did not reveal any motor impairment in the open field. Hepatic, renal and cerebral lipid peroxidation in treated rats did not differ from those in control rats. Conversely, 0.5 micromol/kg of compound 1 decreased lipid peroxidation in spleen. Delta-ALA-D activity in liver and spleen was inhibited in rats treated with the higher dose of compound 1 but no significant differences were detected in renal delta-ALA-D activity. AST (aspartate aminotransferase) and ALT (alanine aminotransferase) activities as well as urea and creatinine levels were increased by high doses of compound 1 (50-75 micromol/kg). Compound 1 induced a significant decrease in plasma triglyceride levels but none of the doses tested changed the cholesterol level. This is a promising compound for more detailed pharmacological studies involving organotellurium compounds.
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PMID:Evaluation of antioxidant activity and potential toxicity of 1-buthyltelurenyl-2-methylthioheptene. 1671 63

A 49-year-old woman with a history of chronic hepatitis C virus infection and Hashimoto disease was admitted to our hospital because of proteinuria, hematuria, purpura, and edema in the lower extremities. Laboratory data on admission revealed proteinuria (0.2 g/day), microscopic hematuria (3+) with RBC casts, renal dysfunction(serum creatinine 1.4 mg/dl), positive anti nuclear antigen (x640, speckled type), hypocoplementemia, mixed cryoglobulinemia (type III), and hepatitis C virus infection (AST 45 IU/l, ALT 33 IU/l). MPO-ANCA level was found to be high (356 EU). In renal biopsy, most glomeruli showed crescentic formation with the weak deposition of IgG, IgM, and C3 in the mesangial area and along the capillary wall. She was diagnosed as having systemic vasculitis associated with MPO ANCA. Methylprednisolone pulse therapy followed by oral prednisolone (40 mg/day) effectively normalized MPO ANCA level. It has been reported that ANCA is found in patients with HCV-associated mixed cryoglobulinemia. Therefore, in chronic hepatitis C patients with systemic vasculitis, we should consider the possibility of ANCA-related microscopic polyangiitis and make a correct diagnosis by renal biopsy.
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PMID:[A case of MPO-ANCA-related microscopic polyangiitis with mixed cryoglobulinemia]. 1678 Jan 8

The protective effect of beta-glucan against oxidative injury caused by acetaminophen was studied in mice liver. BALB-c mice (25-30 g) were pre-treated with beta-d-glucan (50 mg/kg, p.o.) for 10 days and on the 11th day they received an overdose of acetaminophen (900 mg/kg, i.p.). Four hours after the acetaminophen injection, mice were decapitated and their blood was taken to determine serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha) levels. Tissue samples of the liver were taken for histological examination or for the determination of levels of malondialdehyde, an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase activity, an index of tissue neutrophil infiltration. The formation of reactive oxygen species in hepatic tissue samples was monitored by using the chemiluminescence technique with luminol and lucigenin probes. Acetaminophen caused a significant decrease in the GSH level of the tissue, which was accompanied with significant increases in the hepatic luminol and lucigenin chemiluminescence values, malondialdehyde level, MPO activity and collagen content. Similarly, serum ALT, AST levels, as well as LDH and TNF-alpha, were elevated in the acetaminophen-treated group when compared with the control group. On the other hand, beta-d-glucan treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by acetaminophen. In conclusion, these results suggest that beta-d-glucan exerts cytoprotective effects against oxidative injury through its antioxidant properties and may be of therapeutic use in preventing acetaminophen toxicity.
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PMID:Acetaminophen-induced toxicity is prevented by beta-D-glucan treatment in mice. 1682 97


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