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)

This study was designed to examine the effects of aqueous garlic extract (AGE) on hepatic ischaemia-reperfusion (I/R) injury in rats. For this purpose, Wistar albino rats were subjected to 45 min of hepatic ischaemia, followed by a 60-min reperfusion period. AGE (1 mL kg(-1), i. p., corresponding to 500 mg kg(-1)) or saline was administered twice, 15 min before ischaemia and immediately before the reperfusion period. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver functions. Liver tissues were taken for the determination of malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker, was also determined. Plasma ALT and AST activities were elevated in the I/R group as compared with the control group, while these increases were significantly decreased by AGE treatment. Hepatic GSH levels, significantly depressed by I/R, were elevated back to control levels in the AGE-treated I/R group. Increases in tissue MDA levels and MPO activity due to I/R injury were reduced back to control levels by AGE treatment. Similarly, increased hepatic collagen content in the I/R group was reduced to the control level with AGE treatment. Since AGE administration alleviated the I/R-induced injury of the liver and improved the hepatic structure and function, it seems likely that AGE, with its antioxidant and oxidant-scavenging properties, may be of potential therapeutic value in protecting the liver against oxidative injury due to ischaemia-reperfusion.
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PMID:Aqueous garlic extract alleviates ischaemia-reperfusion-induced oxidative hepatic injury in rats. 1563 2

Acetaminophen, a widely used analgesic and antipyretic, is known to cause hepatic and renal injury in humans and experimental animals when administered in high doses. It was reported that these toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. In this study we aimed to investigate the possible beneficial effect of 2-mercaptoethane sulphonate (MESNA), an antioxidant agent, against acetaminophen toxicity in mice. Balb-c mice were injected i.p. with: vehicle (the control group); a single dose of 150 mg kg(-1) MESNA (MES group); a single dose of 900 mg kg(-1) i.p. acetaminophen (AA4h and AA24h groups); and MESNA, at a dose of 150 mg kg(-1) after acetaminophen injection (AA4h-MES and AA24h-MES groups). The MESNA injection was repeated once more 12 h after the first injection in the AA24h-MES group. Blood urea nitrogen, serum creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in blood and glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver and kidney tissues were measured. Tissues also were examined microscopically. Blood urea nitrogen and serum creatinine, which were increased significantly (P < 0.001) following acetaminophen treatment were decreased significantly (P < 0.05-0.001) after treatment with MESNA. The ALT and AST levels were also increased significantly (P < 0.001) after acetaminophen treatment but were not reduced with MESNA. Acetaminophen treatment caused a significant (P < 0.05-0.001) decrease in GSH levels whereas MDA levels and MPO activity were increased in both tissues. These changes were reversed by MESNA treatment. Collagen contents of the liver and kidney tissues were increased by acetaminophen treatment (P < 0.001) and reversed back to the control levels with MESNA. Our results imply that acetaminophen causes oxidative damage in hepatic and renal tissues and that MESNA, via its antioxidant effects, protects these tissues. Therefore, its therapeutic role as a 'tissue injury-limiting agent' must be elucidated further in drug-induced oxidative damage.
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PMID:Protective effects of MESNA (2-mercaptoethane sulphonate) against acetaminophen-induced hepatorenal oxidative damage in mice. 1566 31

There have been many fatal occupational accidents of skin exposure to monochloroacetic acid (MCA). However, there have been no reports of dermatological findings and the lethal consequences have not yet been demonstrated. Therefore, harmful local and systemic effects were investigated after dermal exposure to MCA. A 0.5 mL aliquot of MCA solution (40% w/w) was applied to the abdominal skin of ten 10-week-old male SD rats under anesthesia. The exposure area (25 x 25 mm2) was 1.6% of the total surface area. The dose of MCA per area was 34.1 mg/cm2. Saline was similarly administered to 10 control rats. Histopathological findings after 10 min were observed by light microscopy. Blood samples were collected by exsanguinations from the carotid arteries after 4 h. Skin samples were collected 10 min after the initial exposure. Histological findings showed severe degeneration of collagen bundles in the epidermis and subcutaneous tissues. P(CO2), HCO(3)-, TCO2, BE and glucose levels were decreased in the MCA group. AST, m-AST, ALT, BUN, Cr, NH3, lactic acid, pyruvic acid, RBC, Hb, Hct, total protein and albumin were increased in the MCA group. The burn was determined to be a third-degree burn on the basis of the histopathological findings. The severe toxicity was probably a consequence of the rapid permeability. Biochemical parameters were a consequence of hepatocellular injuries, renal dysfunction, dysglyconeogenesis and dysfunction of ammonia metabolism. MCA reportedly enters the TCA cycle and inhibits aconitase. MCA metabolites also inhibit pyruvate carboxylase in the gluconeogenesis pathway. Therefore, the important serum biochemical abnormalities such as hypoglycemia and lactic acidosis should be monitored to find the acute systemic disorders.
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PMID:Systemic effects and skin injury after experimental dermal exposure to monochloroacetic acid. 1574 77

The aim of this study was to assess the antioxidant and antifibrotic effects of chronic administration of aqueous garlic extract on liver fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission (BDL). Aqueous garlic extract (AGE, 1 ml/kg, i.p., corresponding to 250 mg/kg) or saline was administered for 28 days. At the end of the experiment, rats were killed by decapitation. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver functions and tissue damage, respectively. Tumor necrosis factor-alpha (TNF-alpha) was also assayed in serum samples. Liver tissues were taken for determination of the free radicals, renal malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and 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 AGE treatment. Hepatic GSH levels, significantly depressed by BDL, were elevated back to control levels in AGE-treated BDL group. Increases in tissue free radical and MDA levels and MPO activity due to BDL were reduced back to control levels by AGE treatment. Similarly, increased hepatic collagen content in the BDL rats was reduced to the level of the control group with AGE treatment. Since AGE administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic structure and function, it seems likely that AGE 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:Long-term administration of aqueous garlic extract (AGE) alleviates liver fibrosis and oxidative damage induced by biliary obstruction in rats. 1576 83

Excessive oxidative stress is implicated in hepatic fibrogenesis. Extracts of Salvia miltiorrhiza (Sm) have been shown to protect cells against oxidative stress. In this study we investigated the in vitro and in vivo effects of Sm on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1). The inhibitory effects of Sm (50-400 microg/ml) on TGF-beta1-induced alpha-smooth muscle actin (alpha-SMA) secretion and the mRNA expressions of fibrosis-related genes, including alpha-SMA, connective tissue growth factor (CTGF), and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed. Fibrosis was induced by dimethylnitrosamine (DMN) administration in rats. DMN-treated rats were randomly assigned to 1 of 4 groups: saline, Sm (20 mg/kg), Sm (100 mg/kg), or silymarin (100 mg/kg), each given by gavage twice daily for 5 weeks starting from the onset of DMN administration. Sm (200 and 400 microg/ml) significantly inhibited TGF-beta1-stimulated alpha-SMA secretion and the mRNA expressions of alpha-SMA, CTGF, and TIMP-1 in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats with either a low (1.8 +/- 0.2) or high (1.8 +/- 0.1) dose of Sm, or silymarin (1.4 +/- 0.2) were significantly reduced in comparison with DMN-treated rats receiving saline (3.1 +/- 0.1). Hepatic collagen contents were also significantly reduced by either Sm or silymarin treatment. The mRNA expression levels of alpha-SMA, TGF-beta1, and procollagen I were all attenuated in Sm- and silymarin-treated rats. Moreover, levels of plasma aspartate transaminase activities were reduced by Sm and silymarin treatment. In conclusion, our results show that Sm exerted antifibrotic effects in both HSC-T6 cells and in rats with DMN-induced fibrosis.
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PMID:Antifibrotic effects of Salvia miltiorrhiza on dimethylnitrosamine-intoxicated rats. 1586 49

The aim of this study was to investigate the possible protective effects of aqueous garlic extract (AGE) against naphthalene-induced oxidative changes in liver, kidney, lung and brain of mice. Balb/c mice (25-30 g) of either sex were divided into five groups each comprising 10 animals. Mice received for 30 days: 0.9% NaCl, i.p. (control); corn oil, i.p; AGE in a dose of 125 mg kg-1, i.p.; naphthalene in a dose of 100 mg kg-1, i.p. (dissolved in corn oil); and AGE (in a dose of 125 mg kg-1, i.p.) plus naphthalene (in a dose of 100 mg kg-1, i.p.). After decapitation, liver, kidney, lung and brain tissues were excised. Malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase activity (MPO) were determined in the tissues, while oxidant-induced tissue fibrosis was determined by collagen content. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels and blood urea nitrogen and creatinine concentrations were measured for the evaluation of hepatic and renal function, respectively. MDA and GSH levels were also assayed in serum samples. In the naphthalene-treated group, GSH levels decreased significantly, while MDA levels, MPO activity and collagen content increased in the tissues (P<0.01-0.001), suggesting oxidative organ damage, which was also verified histologically. In the AGE-treated naphthalene group, all of these oxidant responses were reversed significantly (P<0.05-0.01). Hepatic and renal function test parameters, which increased significantly (P<0.001) following naphthalene administration, decreased (P<0.05-0.001) after AGE treatment. The results demonstrate the role of oxidative mechanisms in naphthalene-induced tissue damage. The antioxidant properties of AGE ameliorated oxidative organ injury due to naphthalene toxicity.
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PMID:Protective effect of aqueous garlic extract against naphthalene-induced oxidative stress in mice. 1590 51

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87% accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100%), but with reduction in diagnostic sensitivity (64%). When compared with the criteria of Ratziu et al. for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70%). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.
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PMID:Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease. 1591 56

Thermal injury elicits several systemic consequences, among them the systemic inflammatory response where the generation of reactive oxygen radicals and lipid peroxidation play important roles. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the tissue samples from lung, liver, kidney and skin were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and creatinine, urea (BUN) concentrations were determined to assess liver and kidney function, respectively. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were also assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced damage in remote organs and protects against oxidative organ damage by a neutrophil-dependent mechanism.
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PMID:Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs. 1593 62

DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.
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PMID:Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. 1605 Aug 19

The determination of a possible corrosive or irritative potential of certain products and ingredients is necessary for their classification and labeling requirements. Reconstructed skin as a model system provides fundamental advantages to single cell culture testing and leads to promising results as shown by different validation studies (for review: Fentem, J.H., Botham, P.A., 2002. ECVAM's activities in validating alternative tests for skin corrosion and irritation. ATLA 30(Suppl. 2), 61-67). In this study we introduce our new reconstructed epidermis "Epidermal-Skin-Test" (EST-1,000). This fully grown epidermis consists of proliferating as well as differentiating keratinocytes. EST-1,000 shows a high comparability to normal human skin as shown by histological and immunohistochemical data. Characteristic markers (KI-67, CK 1/10/5/14, transglutaminase, collagen IV, involucrin, beta 1 integrin) can be identified easily. The main focus of this work was to characterize EST-1,000 especially with respect to its barrier function by testing several substances of known corrosive potential. Skin corrosion was detected by the cytotoxic effect of the substances on a reconstructed epidermis after short-term application to the stratum corneum. The effect was determined by standard MTT assay and accompanying histological analysis. Hence EST-1,000 shows a very high predictive potential and closes the gap between animal testing and the established full-thickness model Advanced-Skin-Test 2,000 (AST-2,000) (Noll, M., Merkle, M.-L., Kandsberger, M., Matthes, T., Fuchs, H., Graeve, T., 1999. Reconstructed human skin (AST-2,000) as a tool for pharmaco-toxicology. ATLA 27, 302).
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PMID:Epidermal-skin-test 1,000 (EST-1,000)--a new reconstructed epidermis for in vitro skin corrosivity testing. 1606 50


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