Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, the genotoxic, hematoxic effects, and their relation with pathological and biochemical parameters of hexane were investigated. Cytogenetic evaluation performed on the bone marrow indicated that chromosome aberrations increased at both hexane doses in relation to the negative controls. Decreased hematocrit, hemoglobin concentrations, and mean corpuscular volume were observed on the whole blood counts. Conjugated dienes (CD), glutathione (GSH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and catalase (CAT) were increased. Histological examinations showed intracytoplasmic vacuolisation, nuclei with lower chromatin, and parenchymatous degenerations in the dose groups. In the bone marrow slides, depletion of the erythroid series were observed. In conclusion, hexane seems to be a genotoxic and hematoxic agent leading to degeneration and lipid peroxidation in exposed groups.
Teratog Carcinog Mutagen 2000
PMID:Genotoxic, hematoxic, pathological, and biochemical effects of hexane on Swiss albino rats. 1107 17

Allele-specific competitive blocker PCR (ACB-PCR) amplification and quantification was developed for mouse p53 codon 270 CGT-->TGT base substitution and codon 244/245 AAC/CGC-->AAT/TGC tandem mutation. PCR products corresponding to p53 mutant and wild-type DNA sequences were generated. These DNAs were mixed in known proportions to construct samples with defined mutant fractions and the allele-specific detection of each mutation was systematically optimized. Each assay was used to analyze eight simulated solar light (SSL)-induced tumors. By analyzing mutant fraction (MF) standards in parallel with PCR products generated from tumor samples, p53 mutants could be quantified as subpopulations within the tumors. All eight tumors contained detectable levels of p53 codon 270 CGT-->TGT mutation. Three tumors had p53 MFs between 10(-4) and 10(-3). Five tumors had p53 MFs between 10(-3) and 10(-2). None of the eight mouse skin tumors had measurable levels of p53 codon 244/245 tandem mutation. Frequent detection of p53 codon 270 CGT-->TGT mutation provides additional evidence that a pyrimidine dinucleotide overlapping a methylated CpG site (Pyr(me)CG) is a susceptible target for SSL-induced mutagenesis. The absence of p53 codon 244/245 mutation in tumors may be explained by its mutant p53 phenotype and/or indicate that this site is not methylated. These initial results indicate that p53 codon 270 CGT-->TGT mutation may be a sensitive biomarker for SSL- or UV-induced mutagenesis. This mutational endpoint may be useful for evaluating the co-carcinogenicity of compounds administered in combination with UV or SSL.
Environ Mol Mutagen 2005 Jun
PMID:Quantifying levels of p53 mutation in mouse skin tumors. 1566 16

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.
Environ Mol Mutagen 2006 Aug
PMID:Evaluation of the radioprotective effect of Liv 52 in mice. 1675 71

Bhawalpur is a major cotton-growing area in Pakistan. Cotton picking in Pakistan is carried out by females and as a result of the intensive use of pesticides during the growing season these females are exposed to pesticide residues in the picking season. In the present study, peripheral blood was obtained from 69 cotton pickers and 69 unexposed females and used to assess the effect of pesticide exposure on genetic damage as well as on hepatic enzymes and serum cholinesterase. The subjects were of similar average age in workers and control groups (37.55 +/- 12.75 vs. 37.52 +/- 13.47, P > 0.05). Average exposure time of the picker females was 10.26 +/- 6.14 years. Subjects from the exposed group did not use any protective measures during their work activities. Levels of serum cholinesterase were lower, and levels of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were higher in the exposed workers as compared with the control group (P < 0.001). The exposed group exhibited significantly increased frequencies of binucleated cells with micronuclei (12.72 +/- 3.48 vs. 4.35 +/- 2.44, P < 0.001) and total number of micronuclei in binucleated lymphocytes (16.51 +/- 4.27 vs. 5.86 +/- 3.09, P < 0.001) in comparison with subjects of the control group. The binucleated cells with micronuclei frequency also seemed to increase with age in both the groups, however, the magnitude of increase was greater in exposed group than the control. Results from the present study indicate that occupational exposure to pesticide mixtures results in cytogenetic damage in exposed females.
Environ Mol Mutagen 2008 Jun
PMID:Cytogenetic damage in female Pakistani agricultural workers exposed to pesticides. 1841 70

Nitrogen mustard (HN-2), also known as mechlorethamine, is an alkylating anticancer agent as well as blister inducing chemical warfare agent. We evaluated the cytoprotective efficacy of amifostine, DRDE-07 and their analogues, and other antidotes of mustard agents against HN-2. Administration of 1 LD(50) of HN-2 (20mg/kg) percutaneously, decreased WBC count from 24h onwards. Liver glutathione (GSH) level decreased prominently and the maximum depletion was observed on 7th day post-HN-2 administration. Oxidised glutathione (GSSG) level increased significantly at 24h post-administration and subsequently showed a progressive decrease. Hepatic malondialdehyde (MDA) level and percent DNA damage increased progressively following HN-2 administration. The spleen weight decreased progressively and reached a minimum on 3-4 days with subsequent increase. The antidotes were administered repeatedly for 4 and 8 days after percutaneous administration of single sublethal dose (0.5 and 0.25 LD(50)) of HN-2. Treatment with DRDE-07, DRDE-30 and DRDE-35 significantly protected the changes in spleen weight, WBC count, GSH, GSSG, MDA and DNA damage following HN-2 administration (0.5 and 0.25 LD(50)). There was no alteration in the transaminases (AST and ALT), and alkaline phosphatase (ALP) activities, neither with HN-2 nor with antidotes. The present study shows that HN-2 is highly toxic by percutaneous route and DRDE-07, DRDE-30 and DRDE-35 can partially protect it.
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PMID:DRDE-07 and its analogues as promising cytoprotectants to nitrogen mustard (HN-2)--an alkylating anticancer and chemical warfare agent. 1939 60

A number of pharmacological properties have been attributed to apigenin. In the present study the effect of apigenin was investigated with respect to hepatotoxicity induced by N-nitrosodiethylamine (NDEA), a compound that is present in many food stuffs and has been reported to be a hepatocarcinogen. Male rats were exposed to NDEA (0.1mg/ml) dissolved in drinking-water separately, and with 10, 20, or 40mg/ml of apigenin for 21 days. The activity of glutamic-oxaloacetic transaminase (SGOT), glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) was measured in blood serum. Lipid peroxidation, protein carbonyl content and micronucleus frequency were determined in hepatocytes. To assess the effect on DNA damage, the comet assay was performed on hepatocytes, blood lymphocytes and bone-marrow cells of the exposed rats. The results of the study reveal that the treatment of NDEA together with apigenin showed a significant dose-dependent decrease in the serum concentration of the enzymes SGOT, SGPT, ALP and LDH (p<0.05). Histological sections of the liver also showed a protective effect of apigenin. A significant dose-dependent reduction in lipid peroxidation and protein carbonyl content was observed in rats exposed to NDEA (0.1mg/ml) together with apigenin (p<0.05). The results obtained for the comet assay in rat hepatocytes, blood lymphocytes and bone-marrow cells showed a significant dose-dependent decrease in the mean tail length (p<0.05). The present study supports the role of apigenin as an anti-genotoxic and hepatoprotective agent.
Mutat Res Genet Toxicol Environ Mutagen 2014 Jun
PMID:Protective effect of apigenin against N-nitrosodiethylamine (NDEA)-induced hepatotoxicity in albino rats. 2475 54

J Hamilton currently serves as vice president of Clinical Development at Arrowhead Pharmaceuticals, Inc. (CA, USA), where he is responsible for clinical strategy, clinical trial design, implementation and execution. In this role, he managed the ARC-520, ARC-521 and ARC-AAT global programs. Previously, he was medical director and head of Corporate Development at Arrowhead. He led Arrowhead's acquisition of the Novartis RNAi assets and led Arrowhead's $670 million cardiovascular deal with Amgen (CA, USA). He earned an MD and MBA at The Ohio State University (USA) and is a licensed physician with board certification in emergency medicine. J Hamilton speaks to Hannah Makin, commissioning editor.
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PMID:Overcoming the challenges of RNAi-based therapy: an interview with James Hamilton. 2994 84