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1.
The pyrolusite (beta-MnO2)-mediated oxidation of 2,4,6-trichlorophenol (TCP) under nonaqueous conditions was investigated to assess the potential for abiotic transformations of chlorophenols and their transformation pathways when they are released to soils and the vadose zone. Lower rates of TCP oxidation were found at lower relative humidities, but the rates were still relatively high under near-dry conditions, with 86% of the TCP transformed within 24 h at less than 2% relative humidity. The rates of TCP transformation and soluble manganese formation at less than 2% relative humidity were not affected by atmospheric oxygen content. The manganese oxide-mediated oxidation of TCP resulted in the formation of 2,6-dichloro-1,4-benzoquinone and dimers, including polychlorinated phenoxyphenols and at least one tetrachlorodibenzo-p-dioxin. The products are consistent with the proposed mechanism in which some of the TCP is transformed into trichlorophenoxy radicals that attack TCP and its transformation products. The present results demonstrate that naturally occurring manganese oxides have the potential to oxidize industrial compounds such as TCP; however, the transformation products may be more toxic and persistent than the parent compound.  相似文献   

2.
Herein are reported the synthesis and anticancer activity against the human breast cancer cell line MCF-7 of a series of substituted (RS)-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine derivatives and (RS)-9-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-9H-purine derivatives. When the Mitsunobu reaction was carried out between (RS)-2,3-dihydro-1,4-benzoxathiin-3-methanol and the heterocyclic bases 6-chloro-, 2,6-dichloro, and 6-bromo-purines under microwave-assisted conditions, a formal 1,4-sulfur migration takes place through two consecutive oxyranium and episulfonium rings, giving rise to the corresponding (RS)-9-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-9H-purine derivatives, previously reported by us. The most active compound (RS)-2,6-dichloro-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine shows an IC50 = 2.75 ± 0.02 μM. When the cancerous cells were treated with this compound, a significant increase of apoptotic cells (70.08 ± 0.33%) was obtained in relation to the control ones. The induction of the G2/M cell cycle arrest and apoptosis by the three most active compounds is associated with increased phosphorylation of eIF2α in human breast cancer cells.  相似文献   

3.
The marine diatom Skeletonema costatum was used to study mechanisms of detoxification when submitted to cadmium and copper contamination. After 96 h of growth, concentration corresponding to 50% growth inhibition (IC50, 96 h) was 0.224 mg/L for cadmium and 0.045 mg/L for copper, indicating that copper is more toxic for S. costatum than cadmium. Heavy cellular damages were observed for cadmium and copper concentrations close to the IC50. Exposure to these concentrations induced a migration of inclusions from the peripheral cytoplasm to the vacuole. Electron energy loss spectroscopy (EELS) investigations demonstrated that Cd and Cu were specifically trapped in these inclusions. However, Cu was less sequestered than cadmium in the vacuole. EELS determination of oxidation states evidenced that trace metals were sequestered as Cd2+ and Cu2+. Nitrogen and sulfur are involved in metallic storage, especially in the case of cadmium contamination. Received: 6 August 1996/Revised: 18 February 1997  相似文献   

4.
Southern armyworm, Spodoptera eridania, larvae were provided ad libitum 0.002–0.25% w/w dichlone, 2,3-dichloro-1,4-naphthoquinone (CNQ). Larval mortality occurred in a time-and-dose dependent manner, with an LC17 of 0.01% and an LC50 of 0.26% CNQ at day-5. Extracts of larvae fed control, 0.01, and 0.25% CNQ diets for 5 days were assayed for antioxidant enzymes. While 0.01% CNQ had a mild effect, 0.25% CNQ profoundly increased levels of all antioxidant enzymes that were examined. The increases as compared to control were: 5.3-, 1.9-, 3.2-, 2.6-, 2.8-, and 3.5-fold higher for superoxide dismutase, catalase, glutathione transferase and its peroxidase activity, glutathione reductase and DT-diaphorase, respectively. At 0.01% CNQ, the thiobarbituric acid reactive substances (TBARS) were similar to the control group. However, despite the induction from 0.25% CNQ of all enzymes examined, the lipid peroxidation was not attenuated; the TBARS were 29.7% over the control value. High mortalities and CNQ-induced pathologies reflected in retarded growth, wasting syndrome, and diuresis clearly indicated that the insect sustained severe oxidant-induced injuries before appropriate defenses were fully mobilized. Thus, this quinone causes an oxidative stress in a model insect species analogous to that observed in mammalian species.  相似文献   

5.
不同营养素配方饲料对小鼠抗氧化能力的影响   总被引:1,自引:0,他引:1  
目的:观察3种含有不同量营养元素的饲料(NRC、XYZ、E100)对小鼠抗氧化能力的影响。方法:采用不同配方饲料预先饲养小鼠8周后,给小鼠一定处置,造成氧化损伤,测定脑、心、肝、肾4种组织中脂质过氧化物(TBARS)含量、羰基蛋白含量、谷胱苷肽过氧化物酶(GPX)的活力,CGPx、PHGPx、MnSOD的mRNA表达等指标的变化。结果:以普通饲料NRC饲养的小鼠经处置后,4种组织中的脂质过氧化物、羰基蛋白含量均有不同程度的上升,GPx酶活力下降,CGPx、PHGPx的mRNA表达下调,心与肝的MnSOD的mRNA表达上调,XYZ配方能较好地预防组织氧化损伤,E100的作用较差。结论:精神压力能够引起氧化损伤,不同营养素配方饲料对各项氧化损伤指标的影响不同。  相似文献   

6.
Peroxidase-mediated degradation of perfluorooctanoic acid   总被引:1,自引:0,他引:1  
Concentrations of aqueous-phase perfluorooctanoic acid (PFOA), a representative perfluorinated aliphatic (PFA) compound, are shown to be reduced effectively via reaction with horseradish peroxidase (HRP), hydrogen peroxide, and a phenolic cosubstrate (4-methoxyphenol). Reaction rate profiles are pseudo-first order, yielding an apparent best-fit removal rate constant of k1 = 0.003/min (r2 = 0.96, n = 14). Approximately 68% depletion of the parent compound and 98% depletion of its related acute aquatic toxicity are achieved in 6 h. Because no PFOA removal is observed in the absence of cosubstrate and/or following consumption thereof, we conclude that radical intermediate species generated during reaction between HRP and 4-methoxyphenol mediate nonspecific depletion of PFOA and that these intermediates may be sufficiently reactive to sever the extremely stable C-F bonds of PFOA. These results are consistent with measurements of reaction by-products, including fluoride ion and various aliphatic species of shortened chain length. Based on these findings, we conclude that PFA degradation may occur via one of two mechanisms: Kolbe decarboxylation followed by stepwise conversion of -CF2 units to CO2 and fluoride ion, or radical abstraction from a double bond with subsequent fragmentation. Our results indicate that under appropriate conditions, enzymatic degradation may comprise a natural transformation pathway for PFAs. Moreover, we anticipate that appropriately engineered enzymatic processes may hold promise for treatment of PFOA-contaminated waters. This, to the best of our knowledge, is the first report to substantiate the efficacy of HRP-catalyzed reactions for contaminant removal via degradative reactions versus polymerization reactions.  相似文献   

7.
OBJECTIVE: The protective effects of D-glucaro 1,4-lactone (1,4-GL) against oxidative/nitrative protein damage (determined by parameters such as levels of protein carbonyl groups and nitrotyrosine residues) to human plasma treated with peroxynitrite (ONOO-) or hydroperoxide (H2O2) were studied in vitro. We also investigated the effects of 1,4-GL on the level of total free thiol groups and low-molecular-weight thiols (glutathione and homocysteine) in plasma treated with ONOO- (0.1 mM). METHODS: Levels of carbonyl groups and nitrotyrosine residues in human plasma proteins were measured by ELISA and a competition ELISA, respectively. High-performance liquid chromatography (HPLC) was used to analyze free thiols from plasma. RESULTS: Exposure of plasma to ONOO- (0.1 mM) resulted in an increase of the level of carbonyl groups and nitrotyrosine residues in plasma proteins and in a distinct decrease in total thiols and low-molecular-weight thiols (glutathione and homocysteine) measured by high-performance liquid chromatography. In the presence of 1,4-GL (0.4-6.4 mM), a distinct decrease in carbonyl group formation and tyrosine nitration in plasma proteins and changes in plasma thiols caused by 0.1 mM of peroxynitrite were observed. Moreover, 1,4-GL inhibited plasma protein oxidation induced by H2O2 (2 mM). CONCLUSION: The obtained results indicate that in vitro 1,4-GL has inhibitory effects on ONOO-- or hydroperoxide-mediated oxidative stress in human plasma and changes plasma redox thiol status. The mechanism of the antioxidative action of 1,4-GL present in plasma is not known yet.  相似文献   

8.
Voltage-gated Kv7/KCNQ/M-potassium channels play a pivotal role in controlling neuronal excitability. Genetic reduction of KCNQ channel activity as a result of mutations causes various human diseases such as epilepsy and arrhythmia. Therefore, discovery of small molecules that activate KCNQ channels is an important strategy for clinical intervention of membrane excitability related disorders. In this study, a series of pyrazolo[1,5-a]pyrimidin-7(4H)-ones (PPOs) have been found to be novel activators (openers) of KCNQ2/3 potassium channels through high-throughput screening by using atomic absorption rubidium efflux assay. Based on structure-activity relationship (SAR), the substituted PPOs have been optimized. The 5-(2,6-dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-7(4H)-one (17) was identified as a novel, potent, and selective KCNQ2/3 potassium channel opener by patch-clamp recording assay.  相似文献   

9.
The enantiomers of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzoxathian hydrochloride (1: benoxathian) were prepared from the chiral 1,4-benzoxathian-2-carboxylic acids [(+)- and (−)-3] which in turn were obtained through the resolution of the racemic acid with R- and S-α-methylbenzylamine. Their blocking activities and relative selectivities on α1- and α2-adrenoreceptors were evaluated on isolated rat vas deferens. For α1-adrenoreceptors the enantiomer (−)-1 was 10 times more potent than the enantiomer (+)-1, whereas no significant difference between the blocking activity of the enantiomers was observed for α2-adrenoreceptors. Furthermore, the enantiomer (−)-1 showed high activity and selectivity toward the α1-adrenoreceptor (pA2 = 9.36; selectivity ratio = 1230) which may have relevance in the characterization of α-adrenoreceptor subtypes.  相似文献   

10.
We here report the synthesis and biological evaluation of new 3-[(2-indolyl)]-5-phenyl-3,5-pyridine, 3-[(2-indolyl)]-5-phenyl-2,4-pyridine and 3-[(2-indolyl)]-5-phenyl-2,6-pyrazine derivatives designed as potential CDK inhibitors. Indoles and phenyls were used to generate several substitutions of the pyridine and pyrazine rings. The synthesis included Stille or Suzuki type reactions, which were carried out on the 3,5-dibromopyridine, 2,4-dichloropyridine and 2,6-dichloro-1-4-pyrazine moieties. Cell effects of the V-shaped family were in the micromolar range. Kinase assays were conducted and showed that compound 11 inhibited CDK5 with an inhibitory concentration of 160 nM with a moderate selectivity over GSK3 compared to the reference C which exhibited a slightly lower activity on CDK5 (1.5 μM). Compound 11 was also found to be the most potent compound in the series and was identified as a new lead for DYRK1A inhibitor discovery (IC50 = 60 nM). Docking studies were carried out in order to investigate the inhibition of DYRK1A.  相似文献   

11.
BACKGROUND: Adequate intakes of calcium are required for optimal bone health and protection against chronic disease. Dairy products are an excellent source of calcium. OBJECTIVE: The absorption of calcium from a range of fortified milks was measured in humans with the use of stable isotopes. DESIGN: Fifteen volunteers participated in a randomized, controlled, double-blind crossover study. Five types of semi-skimmed (1.9% fat) milk drinks were administered with a light breakfast: standard milk (control milk); milk enriched with calcium from milk solids and tricalcium phosphate [(TCP) MSS milk]; milk enriched with calcium from concentrated milk (CON milk); milk with added fructo-oligosaccharides [(FOSs) FOS milk]; and milk with added caseinophosphopeptides [(CPPs) CPP milk]. All the milks were labeled with 42Ca as CaCl2. The MSS milk was also labeled with 44Ca as TCP. The quantity of calcium in each drink was kept the same by varying the volume given. RESULTS: Calcium absorption did not differ significantly between the control milk and the calcium-fortified milks (MSS and CON milk) or the FOS and CPP milks. However, calcium absorption from the TCP added to the MSS milk was significantly higher than that from the control milk (27.5 +/- 7.6% and 24.5 +/- 7.3%, respectively; P = 0.003). CONCLUSIONS: Calcium-enriched milks are a valuable source of well-absorbed calcium. Absorption of added calcium as TCP was higher than that of calcium from the control milk, but the addition of FOSs or CPPs did not significantly increase calcium absorption. Further research is needed to ascertain the cost-effectiveness and public health benefits of consuming fortified milks.  相似文献   

12.
Pure cultures of aerobic and anaerobic bacteria capable of oxidation and reductive dehalogenation of chloroethylenes, and aerobic bacteria involved in biodegradation of polychlorinated biphenyls (PCBs) were screened for their ability to cometabolize the persistent pollutant 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE). Bacterial cultures expressing methane monooxygenase (Methylosinus trichosporium), propane monooxygenase (Mycobacterium vaccae) and biphenyl 2,3-dioxygenase enzymes (Pseudomonas fluorescens and Rhodococcus globerulus), as well as bacteria reductively dechlorinating chloroethylenes (Acetobacterium woodii and Clostridium butyricum) could not degrade DDE. Cell-free extracts of M. trichosporium, M. vaccae, P. fluorescens and R. globerulus were also unable to transform DDE, indicating that cell wall and membrane diffusion barriers were not biodegradation limiting. These studies suggest that these bacteria can not degrade DDE, even when provided with cosubstrates that induce chlorophenyl- and dichloroethylene-group transforming enzymes. Received: 20 August 1996/Revised: 9 March 1997  相似文献   

13.
The acute toxicities and hematological effects of menadione (2-methyl-1,4-naphtho-quinone) and dichlone (2,3-dichloro-1,4-naphtho-quinone) were examined in yearling channel catfish (Ictalurus punctatus). These compounds served as models for quinones, which comprise a diverse group of compounds that enter aquatic systems from numerous sources. The 96-hr LC50's measured were 720 g/L and 42 g/L for menadione and dichlone, respectively. In subsequent experiments, fish were exposed for 21 days to concentrations of 0, 0.25, 0.50, and 0.75 times the LC50 value of each compound. For both compounds, generally dose-dependent increases in methemoglobin concentrations and dose-dependent reductions in hemoglobin concentrations and hematocrit ratios were observed. These results are consistent with the hypothesis that these compounds are toxic in part due to their ability to undergo redox cycling and thereby generate reactive oxygen species. However, other modes of action, such as direct enzyme inhibition, may also be important.  相似文献   

14.
ObjectivesThe Program for Prevention and Health Promotion (PPHP) of the Spanish Society of Family and Community Medicine was launched at the end of the 1980s and its main objective is to integrate preventive and health promotion activities in daily clinical practice in primary care. The aim of the present study was to determine the level of compliance with the preventive activities of the PPHP.MethodsWe performed a comprehensive literature search of PPHP publications to assess the implementation and impact of the program.ResultsThe distinct evaluations carried out since the beginning of the program show that both compliance and registration of preventive activities have improved over time. The PPHP has been positively evaluated by both health professionals and patients. Family physicians in Spain carry out preventive activities more often than other European family physicians.ConclusionsThe PHPPS continues to operate 24 years after its initiation. However, some adaptations are needed since the Spanish health system is changing. Proposed modifications are related to accessibility and to providing a more effective response to users. In elderly patients, life expectancy should be assessed and priorities for preventive interventions should be set accordingly.  相似文献   

15.
The aim of this work was to provide basic data on the antioxidant defences in the annelid Eisenia fetida andrei (E. f. a.). Methods for measurement of three antioxidant enzymes—catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)—and of glutathione-S-transferase (GST) were optimized. GPX activity differed according to the substrate used: cumene hydroperoxide (CUOOH) or hydrogen peroxide (H2O2). The effects on the enzyme activities of storage up to 2 months at −80°C, −20°C, and +4°C were evaluated. The subcellular distribution (in cytosol, mitochondrial, and microsomal fractions) was examined. The properties and subcellular distribution of the enzymes and glutathione were also characterized in dissected tissues and body fluids. The GR activity decreased at −80°C and was the only one not stable at this temperature. The four enzymes were localized mainly in the cytosolic fraction. CAT distribution was unusual as it was not associated with peroxisomes, its properties being consistent with a catalase-peroxidase, rather than a true catalase. However, this result could also be an artifact linked to the use of an inappropriate method to obtain the fractions. Our observations indicate the presence of a distinct cytosolic selenium-dependent GPX (Se-GPX), and of a possible microsomal Se-GPX. A strong non–Se-GPX activity was measured in the CF and CL, which could be linked to the peroxidase activity of fetidins secreted by coelomocytes and with the ROS production of these cells. This study seems to indicate that E. f. a. is well equipped for the metabolism of electrophilic and pro-oxidants through glutathione. Received: 18 February 1998/Accepted: 11 June 1998  相似文献   

16.
目的研究饮用水中2,6-二氯-1,4-苯醌(2,6-DCBQ)对小鼠的急性毒性和遗传毒性作用。方法选择健康6~8周龄SPF级昆明小鼠进行试验。将50只小鼠随机分为5组,分别为阴性对照(玉米油)组和215、464、1 000、2 150 mg/kg 2,6-DCBQ染毒组,每组10只,雌雄各半。采用一次性经口灌胃方式进行染毒,染毒容量为20 ml/kg。染毒后观察14 d,记录动物死亡数,计算其半数致死剂量(median lethal dose,LD50)。将50只小鼠随机分为5组,分别为溶剂对照(玉米油)组和62.5、125和250 mg/kg 2,6-DCBQ染毒组及阳性对照组(40 mg/kg环磷酰胺),每组10只,雌雄各半。采用灌胃方式进行染毒,染毒容量为20 ml/kg,两次灌胃间隔24 h;第二次灌胃后6 h,进行骨髓细胞微核试验。将50只雄性小鼠随机分为5组,分别为溶剂对照(玉米油)组和62.5、125和250 mg/kg 2,6-DCBQ染毒组及阳性对照组(40 mg/kg环磷酰胺),每组10只。采用经口灌胃方式进行染毒,染毒容量为20 ml/kg,连续灌胃5 d。染毒后第35天,进行精子畸形试验。结果 2,6-DCBQ对雄性、雌性小鼠经口急性毒性的LD50分别为501 mg/kg(95%CI:344~730 mg/kg)和584 mg/kg(95%CI:430~794mg/kg)。不同剂量2,6-DCBQ染毒组小鼠的骨髓细胞微核率及精子畸形率与溶剂对照组比较,差异均无统计学意义(P0.05)。各组PCE/NCE值均在正常范围内。结论 2,6-DCBQ对小鼠经口急性毒性属于低毒级,且未发现其具有遗传毒性。  相似文献   

17.
磷脂的过氧化过程与多种疾病有关,包括炎症、动脉粥样硬化、神经退行性变化、衰老等。磷脂氢谷胱甘肽过氧化物酶是目前发现唯一可以直接减少膜系统及脂蛋白上的磷脂氢过氧化物,联合维生素E可抑制磷脂过氧化。磷脂氢谷胱甘肽过氧化物酶是谷胱甘肽过氧化物酶家族中的第2个被鉴定的含硒酶,是相对分子质量为19000(M r)的单体酶,其基因位于人类19号染色体上。磷脂氢谷胱甘肽过氧化物酶曾被认为是一种保护质膜的普通的抗氧化酶,现在认为具有多种功能,与人类多种疾病的发生发展有关。  相似文献   

18.
Hydroxytyrosol, tyrosol and caffeic acid effects on hydrogen peroxide-induced DNA damage, hydroperoxide generation and redox enzyme gene expression were studied in oxidative-stress-sensitive human prostate cells (PC3). Hydroxytyrosol led to lower levels of hydroperoxides, DNA damage, and mRNA levels of classic glutathione peroxidase (GPx) for all the studied concentrations. Only hydroxytyrosol was effective at low concentrations (10 microm). Tyrosol reduced DNA oxidation only at high (>50 microm) concentrations and increased hydroperoxides, GPx and phospholipid hydroperoxide GPx mRNA levels. Caffeic acid elicited effects between those of the other two phenolics. Results indicate that hydroxytyrosol is the only significant antioxidant phenolic in olive oil and may be the major component accounting for its beneficial properties. Tyrosol appeared to exhibit pro-oxidant effects (only at high concentrations) and caffeic acid was neutral. Both number and position of hydroxyl groups appear to play a role in the cellular effects of hydroxytyrosol.  相似文献   

19.
Series of new mixed aza-oxo-thia macrocyclic ligands 1,9(2,6)-ditriazina-2,8,10,16-tetraaza-3,7,11,15-tetraoxo-5,13-dithia-cyclohexadecaphan-14,94-diphenyl (L1); 1,10(2,6)-ditri azina-2,9,11,18-tetraaza-3,8,12,17-tetraoxo-5,6,14,15-tetrathia-cyclooctadecaphan-14,104-diphenyl (L2); 1,11(2,6)-ditriazina-2,10,12,20-tetraaza-3,9,13,19-tetraoxo-6,16-dithia-cyclocosa-phan-14,114-diphenyl (L3); 1,12(2,6)-ditriazina-2,11,13,22-tetraaza-3,10,14,21-tetraoxo-6,7,17,18-tetrathia-cyclodocosaphan-14,124-diphenyl (L4) were synthesised. The structural features of the compounds have been studied by elemental analyses, Mass, FT-Raman, FT-IR, 1H and 13C NMR spectroscopy. The antimicrobial activities of the ligands were evaluated using disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against several bacteria and yeast cultures. The obtained results from both methods were assessed in side-by-side comparison with commercial antibacterial and antifungal agents. In most cases, the compounds show strong antifungal activity in the comparison tests. Cytotoxic activities of the ligands against two different human cancer cell lines, stomach (23132/87) and lung (A549) were determined by MTT assay. DNA fragmentation assay tested cell lines were used to analyze the DNA ladder formation which is a characteristic of apoptotic cell death. The binding of the ligands with calf thymus DNA (CT-DNA) has also been investigated by absorption spectroscopy.  相似文献   

20.
Fipronil, {5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile} is commonly applied to soil to protect structures against termite infestations. The fate and bioavailability of fipronil in soil is dependent upon the variability of sorption processes and will differ from soil to soil. Adsorption of fipronil to three Nebraska soils with varying organic matter (OM) content was determined. At the concentrations tested (0.025, 0.1, 0.25, 0.5, 1.0, 1.5, and 2.0 mg L−1), adsorption curves showed constant partitioning of fipronil to the soil matrices (r 2 = 0.998 − 0.999). Calculated organic carbon partitioning coefficients (K oc) ranged from 244 to 628 with an average K oc of 396. Reported K d and K f values increased with increasing organic matter content. Desorption hysteresis was observed as fipronil has a propensity to stay in the adsorbed state. After five soil washes with 0.003 M CaCl2, ~30% of adsorbed fipronil residues were desorbed. Reported K oc values for fipronil suggests that it has intermediate mobility in the field collected soils utilized in this study.  相似文献   

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