Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gentamicin (GM) is one of the most important of the aminoglycoside antibiotics used widely for the treatment of serious and life-threatening infections and whose clinical use is limited by its nephrotoxicity. As the pathogenesis of GM-induced renal dysfunction and injury involves reactive oxygen species, the polyphenolic constituents of soybean with antioxidant property may protect against GM-induced renal toxicity. We therefore tested this hypothesis using phenolic extract of soybean (PESB) on GM-induced nephrotoxicity rat model. Administration of GM (80 mg/kg, s.c.) for 12 days to rats induced marked renal failure, characterized by a significantly increased plasma creatinine, urea and Na(+) ions levels, with K(+) depletion. This was also associated with decreases in the activity of the renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)] measured and depletion of both blood and renal reduced glutathione (GSH) levels. The activities of membrane-bound glucose-6-phosphatase (G6Pase) and 5(1)-nucleotidase (5(1)-NTD) enzymes as well as gamma-glutamyltransferase (gamma-GT) and aspartate aminotransferase (AST) (enzymes that are located in the proximal tubule) were decreased. Renal histology examination further confirmed the damage to the kidney as it reveals severe necrosis of the proximal renal tubules with deposition of colloid casts. These alterations were ameliorated in rats pretreated with PESB. The decrease in the activities of SOD, CAT, GST as well as GSH depletion observed in GM-treated rats was prevented in the rats pretreated with PESB. The activities of gamma-GT, AST and G6Pase were also increased in the kidney. These protective effects were dose dependent except for G6Pase activity and GSH levels that were preserved only at 500 mg/kg dose of PESB, and 5'-NTD activity that was dose dependently decreased. Furthermore, the extent of tubular damage induced by GM was reduced in rats that also received PESB. The lower dose (500 mg/kg) of the extract, however, appeared to provide better histological protection. These results suggest that the PESB has protective effects on GM-mediated nephropathy and this may be related to the action of the antioxidant polyphenolic content of the soybean.
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PMID:Modulation of gentamicin-induced renal dysfunction and injury by the phenolic extract of soybean (Glycine max). 1667 61

Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of detoxication, antioxidation, and antimutation. In this study, we evaluated the antihepatotoxic effect of PBL extract on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Fibrosis and hepatic damage, as reveled by histology and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were induced in rats by an administration of CCl(4) (8%, 1 ml/kg body weight) thrice a week for 4 weeks. PBL extract significantly inhibited the elevated AST and ALT activities caused by CCl(4) intoxication. It also attenuated total glutathione S-transferase (GST) activity and GST alpha isoform activity, and on the other hand, enhanced superoxide dismutase (SOD) and catalase (CAT) activities. The histological examination showed the PBL extract protected liver from the damage induced by CCl(4) by decreasing alpha-smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. The data of this study support a chemopreventive potential of PBL against liver fibrosis.
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PMID:Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats. 1667 62

Changes in the serum proteome were identified during early, fulminant, and recovery phases of liver injury from acetaminophen in the rat. Male F344 rats received a single, noninjury dose or a high, injury-producing dose of acetaminophen for evaluation at 6 to 120 h. Two-dimensional gel electrophoresis of immunodepleted serum separated approximately 800 stained proteins per sample from which differentially expressed proteins were identified by mass spectrometry. Serum alanine aminotransferase/aspartate aminotransferase levels and histopathology revealed the greatest liver damage at 24 and 48 h after high-dose acetaminophen corresponding to the time of greatest serum protein alterations. After 24 h, 68 serum proteins were significantly altered of which 23 proteins were increased by >5-fold and 20 proteins were newly present compared with controls. Only minimal changes in serum proteins were noted at the low dose without any histopathology. Of the 54 total protein isoforms identified by mass spectrometry, gene ontology processes for 38 unique serum proteins revealed involvement of acute phase response, coagulation, protein degradation, intermediary metabolism, and various carrier proteins. Elevated serum tumor necrosis factor-alpha from 24 to 48 h suggested a mild inflammatory response accompanied by increased antioxidant capability demonstrated by increased serum catalase activity. Antibody array and enzyme-linked immunosorbent assay analyses also showed elevation in the chemokine monocyte chemoattractant protein-1 and the metalloprotease inhibitor tissue inhibitor of metalloproteinases-1 during this same period of liver injury. This study demonstrates that serum proteome alterations probably reflect both liver damage and a concerted, complex response of the body for organ repair and recovery during acute hepatic injury.
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PMID:Alterations in the rat serum proteome during liver injury from acetaminophen exposure. 1668 75

The antimutagenic activity of the methanolic extract of the fruiting bodies of Ganoderma lucidum (Fr.) P. Krast. occurring in South India was investigated. The activity was assayed by Ames Salmonella mutagenicity test using histidine mutants of Salmonella typhimurium tester strains, TA98, TA100 and TA102. The methanolic extract of the mushroom significantly inhibited (P<0.001) the in vitro sodium azide (NaN(3)), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitro-o-phenylenediamine (NPD), and benzo[a]pyrene (B[a]P) induced his(+) revertants in a dose dependent manner. In vivo antimutagenic activity of extract was also assayed by determining the mutagenicity of the urine of rats administrated with B[a]P as a mutagen. The prior administration of extract markedly inhibited mutagenicity induced by B[a]P. The results indicated that the methanolic extract of Ganoderma lucidum occurring in South India possessed significant antimutagenic activity. The effect of B[a]P on hepatic enzymes, such as serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphtase (ALP), were also evaluated. The extract prevented the increase of SGOT, SGPT, and ALP activities consequent to B[a]P challenge, and enhanced the levels of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT). The extract also profoundly inhibited lipid peroxidation induced by B[a]P. The results revealed that Ganoderma lucidum extract restored antioxidant defense and prevented hepatic damage consequent to the challenge by B[a]P.
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PMID:Antimutagenic activity of methanolic extract of Ganoderma lucidum and its effect on hepatic damage caused by benzo[a]pyrene. 1671 54

The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. The present study was conducted to evaluate the potential toxicity of long time oral exposure to diphenyl diselenide (PhSe)2 in rabbits. Male adult New Zealand rabbits were divided into four groups, group I served as control; groups II, III and IV received 0.3, 3.0 and 30 ppm of (PhSe)2 pulverized in the chow for 8 months. A number of parameters were examined in blood as indicators of toxicity, including delta-aminolevulinate dehydratase (delta-ALA-D), catalase, glutathione peroxidase (GPx), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine, TBARS, non-protein-SH, ascorbic acid and selenium. The results demonstrated that 6 and 8 months of 30 ppm (PhSe)2 intake caused a significant increase in blood delta-ALA-D activity. Erythrocyte non-protein thiol levels were significantly increased after 2 months of 30 ppm (PhSe)2 intake and then return to control levels after prolonged periods of intake. Ingestion of 3.0 ppm of (PhSe)2 for 8 months significantly increased catalase activity in erythrocytes. Conversely, no alterations in GPx, ALT, AST, TBARS and selenium levels were observed in rabbit serum, conversely, selenium levels in peri-renal adipose tissue were significantly increased after 8 months of 30 ppm (PhSe)2 intake, indicating its great lipophylicity. The present results suggest that diphenyl diselenide was not hepato- or renotoxic for rabbits, but caused some biochemical alterations that can be related to some pro-oxidant activity of the compound (particularly the reduction in Vitamin C).
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PMID:Changes in biochemical parameters in rabbits blood after oral exposure to diphenyl diselenide for long periods. 1673 89

Liv 52 is a mixture of botanicals that is used clinically to treat various hepatic disorders. In this study, the radioprotective activity of Liv 52 was evaluated in mice given whole-body exposure to different doses of gamma-radiation. In addition, a series of studies was conducted to explore the mechanism of radioprotection. Radioprotection was evaluated by the ability of Liv 52 to reduce both the frequency of bone marrow micronucleated erythrocytes and the lethality produced by (60)Co gamma-radiation. Mice were treated by oral gavage once daily for seven consecutive days with 500 mg/kg body weight Liv 52 or carboxymethylcellulose vehicle prior to radiation. Micronucleated polychromatic erythrocytes (MPCEs), micronucleated normochromatic erythrocytes (MNCEs), and the PCE/NCE ratio were measured at 0.25-14 days after exposure to whole-body radiation doses of 0, 0.5, 1.5, 3.0, or 4.5 Gy; animal survival was monitored after doses of 7, 8, 9, 10, 11, or 12 Gy. Pretreatment of mice with Liv 52 significantly reduced the frequency of radiation-induced MPCEs and MNCEs. Irradiation reduced the PCE/NCE ratio in a dose-related manner for up to 7 days following irradiation; Liv 52 pretreatment significantly mitigated against these reductions. Liv 52 treatment also reduced the symptoms of radiation sickness and increased mouse survival 10 and 30 days after irradiation. Liv 52 pretreatment elevated the levels of reduced glutathione (GSH), increased the activities of glutathione transferase, GSH peroxidase, GSH reductase, superoxide dismutase, and catalase, and lowered lipid peroxidation (LPx) and the activities of alanine amino transferase and aspartate aminotransferase 30 min after exposure to 7 Gy of gamma-radiation. Liv 52 pretreatment also reduced radiation-induced LPx and increased GSH concentration 31 days following the exposure. The results of this study indicate that pretreatment with Liv 52 reduces the genotoxic and lethal effects of gamma-irradiation in mice and suggest that this radioprotection may be afforded by reducing the toxic effects of the oxidative products of irradiation.
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PMID:Evaluation of the radioprotective effect of Liv 52 in mice. 1675 71

Monosodium glutamate (MSG) continues to function as a flavor enhancer in West African and Asian diets. The present study examines the modulatory effects of dietary antioxidant vitamin C (VIT C), vitamin E (VIT E) and quercetin on MSG-induced oxidative damage in the liver, kidney and brain of rats. In addition, the effect of these antioxidants on the possible genotoxicity of MSG was investigated in a rat bone marrow micronuclei model. MSG administered intraperitoneally at a dose of 4 mg/g body wt markedly increase malondialdehyde (MDA) formation in the liver, the kidney and brain of rats. Simultaneous administration of VIT C, VIT E and quercetin to MSG-treated rats significantly reduced this increase in MDA induced by MSG. VIT E reduced lipid peroxidation most in the liver followed by VIT C and then quercetin, while VIT C and quercetin showed a greater ability to protect the brain from membrane damage than VIT E. The decreased glutathione (GSH) level elicited by MSG in the three organs corresponded with marked increase in the activity of glutathione-S-transferase (GST). While MSG increased (P < 0.001) the activities of superoxide dismutase and catalase in the liver, it decreased significantly the activities of these enzymes in the kidney and the brain. The three antioxidants were effective at ameliorating the effects of MSG on GSH levels and the enzymes in the three organs examined. While MSG increased the activity of glucose-6-phosphatase in the liver and kidneys of rats (P < 0.001), the activity of the enzyme was abysmally low in the brain. There were marked increases in the activities of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase in rats treated with MSG. The antioxidants tested protected against MSG-induced liver toxicity significantly. MSG at a dose of 4 mg/g significantly (P < 0.01) induced the formation of micronucleated polychromatic erythrocytes (MNPCEs). Co-treatment of rats with VIT C and quercetin inhibited the induction of MNPCEs by MSG (P < 0.001). VIT E failed to protect against MSG-induced genotoxicity. The results indicate that dietary antioxidants have protective potential against oxidative stress induced by MSG and, in addition, suggest that active oxygen species may play an important role in its genotoxicity.
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PMID:Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C, vitamin E and quercetin. 1802 56

While radiation hazards, due to free radical generation, present an enormous challenge for biological and medical safety, melatonin is a potent scavenger of a variety of free radicals. The aim of this study was to investigate the radioprotective effect of melatonin against oxidative stress and tissue injury induced by gamma radiation. Rats were subjected to two doses of 2 and 4Gy from cesium-137 source. Four days prior to irradiation, animals received melatonin daily (10mg/kg body weight i.p.). In the irradiated animals, the oxidative stress markers malondialdehyde (MDA) and protein carbonyl were significantly increased in the liver, while a marked decrease in hepatic contents of DNA, RNA, and glutathione (GSH) as well as activity of glutathione-S-transferase (GST) was demonstrated. In addition, catalase (CAT) activity was increased in the liver 5 days after irradiation. The levels of total lipids, cholesterol, triglyceride (TG), low-density lipoprotein (LDL), urea, and creatinine, as well as activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT), were significantly increased in sera of the irradiated rats. This is coupled with decreased serum levels of high-density lipoprotein (HDL), total protein and albumin, and total globulins by irradiation. The administration of melatonin alone daily for 4 days caused significant decreases in MDA and protein carbonyl content and produced significant elevations of GSH content and GST activity in the liver. Moreover, significant decreases in total lipids, cholesterol, and TG without change in LDL or HDL levels in serum were demonstrated. Treatment with melatonin for 4 days before acute irradiation significantly abolished radiation-induced elevations in MDA and protein carbonyl levels in the liver and significantly maintained hepatic GSH content, GST, and CAT activities close to the control values. Preirradiation treatment with melatonin showed significantly higher hepatic DNA and RNA contents than irradiated rats. The levels of total lipids, cholesterol, TG, HDL, LDL, total proteins, albumin, total globulins, creatinine, and urea, as well as the activities of AST, ALT, and GGT in serum were significantly ameliorated when melatonin was injected before irradiation. In conclusion, the increase in oxidative stress markers and the concomitant change in antioxidant levels indicate the role of oxidative stress in radiation-induced tissue damage. Moreover, melatonin shows a radioprotective impact against ionizing-radiation-induced oxidative stress and organ injury.
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PMID:Ameliorative effect of melatonin against gamma-irradiation-induced oxidative stress and tissue injury. 1679 35

The antioxidant potential of crude extracts and fractions from leaves of Ouratea parviflora, a Brazilian medicinal plant used for the treatment of inflammatory diseases, was investigated in vitro through the scavenging of radicals 2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), hydroxyl radical (HO*), superoxide anion (O2*-), and lipid peroxidation in rat liver homogenate. The crude extract (CEOP) and hydro-alcoholic fraction (OP4) showed strong inhibitory activity toward lipid peroxidation induced by tert-butyl peroxide (IC50 = 2.3 +/- 0.2 and 1.9 +/- 0.1 microg/ml, respectively). The same products exhibited a strong concentration-dependent inhibition of deoxyribose oxidation (14.9 +/- 0.2 and 0.2 +/- 0.1 microg/ml, respectively), and also showed a considerable antioxidant activity against O2*- (87.3 +/- 0.1 and 73.1 +/- 0.4 microg/ml, respectively) and DPPH radicals (55.4 +/- 0.3 and 38.3 +/- 0.4 microg/ml, respectively). The protective effects of CEOP and OP4 were also studied in mouse liver. CCl4 significantly increased (by 90%) levels of lipid hydroperoxides, carbonyl protein content (64%), DNA damage index (133%), aspartate aminotransferase (261%), alanine aminotransferase (212%), catalase activity (23%), and also caused a decrease of 60% in GSH content. The results showed that CEOP and OP4 exerted cytoprotective effects against oxidative injury caused by CCl4 in rat liver, probably related to the antioxidant activity showed by the in vitro free radical scavenging property.
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PMID:Free-radical scavenging by Ouratea parviflora in experimentally-induced liver injuries. 1680 67

The objective of this study was to evaluate the protective immunity of excretory-secretory products of Fasciola hepatica (FhES) worm against S.mansoni infection in mice. Evaluation of FhES antigen was through measuring worm burden, ova count, granuloma size and frequency as well as the histopathological picture of the liver. The study was extended to determine the level of free radical scavengers; lipid peroxide, glutathione (GSH), vitamin C, vitamin E, catalase and superoxide dismutase (SOD). Liver function enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were also taken into consideration. Four groups of eight mice each were selected for this study. Group 1 served as control group. Group 2: normal healthy mice vaccinated with FhES product. Group 3: S.mansoni infected mice for 2 months and group 4: infected mice pre-vaccinated with FhES antigen. Vaccination schedule comprised of a single subcutaneous injection of FhES antigen emulsified with Freund's complete adjuvant in a dose 0.5 mg protein/mouse, followed by intraperitoneal injections of the same antigen without adjuvant in 3 doses/week for 3 successive weeks. The total antigen inoculation was 5 mg protein/mouse. The present results revealed a drastic change in all the measured parameters after S.mansoni infection and a noticeable improved level after vaccination with FhES antigen. It can be concluded that FhES antigen succeeded to protect mice against schistosomiasis by a significant reduction in worm burden, ova count, granuloma size and number, improvement in the histopathological architecture of the liver as well as amelioration in the antioxidant levels under investigation.
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PMID:Excretory-secretory product of fasciola hepatica worm protects against Schistosoma mansoni infection in mice. 1687 44


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