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1.
Antioxid Redox Signal ; 30(11): 1432-1449, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29869529

RESUMO

AIMS: Pharmacological treatments for Alzheimer's disease (AD) have not resulted in desirable clinical efficacy over 100 years. Hydrogen peroxide (H2O2), a reactive and the most stable compound of reactive oxygen species, contributes to oxidative stress in AD patients. In this study, we designed a medical device to emit red light at 630 ± 15 nm from a light-emitting diode (LED-RL) and investigated whether the LED-RL reduces brain H2O2 levels and improves memory in senescence-accelerated prone 8 mouse (SAMP8) model of age-related dementia. RESULTS: We found that age-associated H2O2 directly inhibited formaldehyde dehydrogenase (FDH). FDH inactivity and semicarbazide-sensitive amine oxidase (SSAO) disorder resulted in endogenous formaldehyde (FA) accumulation. Unexpectedly, excess FA, in turn, caused acetylcholine (Ach) deficiency by inhibiting choline acetyltransferase (ChAT) activity in vitro and in vivo. Interestingly, the 630 nm red light can penetrate the skull and the abdomen with light penetration rates of ∼49% and ∼43%, respectively. Illumination with LED-RL markedly activated both catalase and FDH in the brains, cultured cells, and purified protein solutions, all reduced brain H2O2 and FA levels and restored brain Ach contents. Consequently, LED-RL not only prevented early-stage memory decline but also rescued late-stage memory deficits in SAMP8 mice. INNOVATION: We developed a phototherapeutic device with 630 nm red light, and this LED-RL reduced brain H2O2 levels and reversed age-related memory disorders. CONCLUSIONS: The phototherapy of LED-RL has low photo toxicity and high rate of tissue penetration and noninvasively reverses aging-associated cognitive decline. This finding opens a promising opportunity to translate LED-RL into clinical treatment for patients with dementia. Antioxid. Redox Signal. 00, 000-000.


Assuntos
Aldeído Oxirredutases/metabolismo , Catalase/metabolismo , Formaldeído/metabolismo , Luz , Memória/efeitos da radiação , Estresse Oxidativo/efeitos da radiação , Animais , Modelos Animais de Doenças , Formaldeído/efeitos adversos , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/terapia , Camundongos
2.
Int Heart J ; 58(5): 769-777, 2017 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-28966308

RESUMO

In this study, we investigated the protection effect of Vitamin E (Vit E) on formaldehyde (FA) exposure during pregnancy induced apoptosis of cardiomyocytes, and used an HL-1 cell line to confirmed the findings in vivo.Pregnant mice received different doses of FA (0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 0.1 µg Vit E, or 1.5 mg/kg + 0.1 µg Vit E). TUNEL staining was used to reveal the apoptosis in cardiomyocytes, and SOD, MDA, GSH, Livin, and Caspase-3 in cardiomyocytes were detected by ELISA, RT-PCR, and Western blot. For in vitro study, HL-1 cells were treated with vehicle, 5 µmol/L FA, 25 µmol/L FA, 50 µmol/L FA, 10 mg/L Vit. E, and 50 µmol/L FA+ 10 mg/L Vit E, respectively. CCK-8 assay and flow cytometry were used to evaluate cell vitality and apoptosis. A high dose of FA exposure led to cytotoxicity in both pregnant mice and offspring, as TUNEL staining revealed a significant apoptosis of cardiomyocytes, and the alternation in SOD, GSH, MDA, Livin, and Caspase-3 was found in cardiomyocytes. 0.1 µg Vit. E could reverse high doses of FA exposure induced apoptosis of cardiomyocytes in both pregnant mice and offspring. The in vitro study revealed that FA exposure induced a decrease of cell viability and increased cell apoptosis, as well as oxidative stress in HL-1 cells with alternation in SOD, GSH, MDA, Livin, and Caspase-3.This study revealed a high dose of FA induced oxidative stress and apoptosis of cardiomyocytes in both pregnant mice and offspring, and Vit E supplement during pregnancy reversed the systemic and myocardial toxicity of FA.


Assuntos
Apoptose/efeitos dos fármacos , Formaldeído/efeitos adversos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Prenhez , Hipersensibilidade Respiratória/tratamento farmacológico , Vitamina E/farmacologia , Animais , Animais Recém-Nascidos , Antioxidantes/farmacologia , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Formaldeído/metabolismo , Formaldeído/toxicidade , Marcação In Situ das Extremidades Cortadas , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Superóxido Dismutase/metabolismo
3.
Nature ; 548(7669): 549-554, 2017 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-28813411

RESUMO

The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair. Notably, formaldehyde is generated from oxidative decomposition of the folate backbone. Furthermore, we find that formaldehyde detoxification in human cells generates formate, and thereby promotes nucleotide synthesis. This supply of 1C units is sufficient to sustain the growth of cells that are unable to use serine, which is the predominant source of 1C units. These findings identify an unexpected source of formaldehyde and, more generally, indicate that the detoxification of this ubiquitous endogenous genotoxin creates a benign 1C unit that can sustain essential metabolism.


Assuntos
Carbono/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Formaldeído/química , Formaldeído/metabolismo , Redes e Vias Metabólicas , Mutagênicos/química , Mutagênicos/metabolismo , Álcool Desidrogenase/metabolismo , Animais , Carbono/deficiência , Linhagem Celular , Galinhas , Coenzimas/metabolismo , Reagentes de Ligações Cruzadas/metabolismo , Dano ao DNA , Reparo do DNA , Humanos , Inativação Metabólica , Camundongos , Nucleotídeos/biossíntese , Oxirredução , Serina/química , Serina/metabolismo , Tetra-Hidrofolatos/metabolismo
4.
J Immunotoxicol ; 13(1): 127-35, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25738525

RESUMO

Inflammation is a local defensive reaction of a host to cellular injury or infection. Prolonged inflammation can contribute to pathogenesis of many disorders. Identification of naturally occurring phytoconstituents that can suppress inflammatory mediators can lead to the discovery of anti-inflammatory therapeutics. Acacia ferruginea is used traditionally to treat numerous ailments including hemorrhage, irritable bowel syndrome and leprosy. The present study evaluated the anti-inflammatory activity of A. ferruginea extract against acute (carrageenan) and chronic (formaldehyde) inflammation in Balb/c mice. Pre-treatment with A. ferruginea extract (10 mg/kg BW) for 5 consecutive days via intraperitonial (IP) administration significantly inhibited subsequent induction of paw edema in both models; the effects were comparable to that of the standard drug indomethacin. The results also showed the A. ferruginea extract significantly inhibited nitric oxide (NO) synthesis and iNOS expression (as measured in serum), diminished inflammation in - and neutrophil infiltration to - the paw tissues and led to a reduction in the number of COX-2(+) immunoreative cells (as evidenced by histologic and immunohistochemical analyses) in the paws relative to those in paws of mice that received the irritants only. Further, in vitro studies showed the extract could significantly scavenge free radicals generated as in DPPH and NO radical generating assays. Taken together, the results showed that A. ferruginea extract imparted potent anti-oxidant and -inflammatory effects, in part by maintaining oxidative homeostasis, inhibiting NO synthesis and suppressing iNOS and COX-2 expression and so could potentially be exploited as a potential plant-based medication against inflammatory disorders.


Assuntos
Acacia/imunologia , Anti-Inflamatórios/administração & dosagem , Ciclo-Oxigenase 2/metabolismo , Inflamação/terapia , Óxido Nítrico Sintase Tipo II/metabolismo , Fitoterapia , Extratos Vegetais/administração & dosagem , Doença Aguda , Animais , Carragenina/metabolismo , Doença Crônica , Ciclo-Oxigenase 2/genética , Formaldeído/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Indometacina/administração & dosagem , Inflamação/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/genética
5.
J Hazard Mater ; 291: 120-8, 2015 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-25771217

RESUMO

The foliar uptake and transport of formaldehyde into Bracket plants from air via leaves and roots to external water was investigated in an air-plant-water system. The results indicated that formaldehyde could be quickly taken up by plant tissues, and that formaldehyde accumulated in leaves could be released rapidly back into air when the formaldehyde level in air was diminished. This rapid reversible translocation of formaldehyde between plant leaves and air resulted in high formaldehyde concentrations in leaf dews, depending upon exposure levels of formaldehyde in air. Meanwhile, formaldehyde could be transported from air to plant rhizosphere solution through downward transport. The concentration of formaldehyde in rhizosphere solutions increased with exposure time and the formaldehyde level in air. The efficiency of the leaf extracts to break down formaldehyde increased, probably because of an increase in oxidative potential of the leaf extracts. Taken together, the main mechanism of formaldehyde loss in air can be attributed to the accumulation by (or breakdown in) plant tissues; the removal rate of formaldehyde from air reached 135 µg h(-1) plant(-1) in the experimental condition.


Assuntos
Poluentes Atmosféricos/isolamento & purificação , Formaldeído/isolamento & purificação , Formaldeído/metabolismo , Liliaceae/metabolismo , Folhas de Planta/metabolismo , Transporte Biológico , Oxirredução , Extratos Vegetais/química , Rizosfera , Plântula/metabolismo , Volatilização
6.
J Biol Chem ; 288(40): 28997-9012, 2013 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-23928311

RESUMO

In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy.


Assuntos
Benzilisoquinolinas/metabolismo , Biocatálise , Dioxigenases/metabolismo , Ópio/metabolismo , Papaver/enzimologia , Benzilisoquinolinas/química , Alcaloides de Berberina/química , Alcaloides de Berberina/metabolismo , Cromatografia Líquida , Formaldeído/metabolismo , Inativação Gênica , Cinética , Espectrometria de Massas , Metilação , Filogenia , Especificidade por Substrato , Vírus
7.
Orv Hetil ; 154(30): 1180-7, 2013 Jul 28.
Artigo em Húngaro | MEDLINE | ID: mdl-23876615

RESUMO

INTRODUCTION: Transmethylation modifies configuration and proceeds via formaldehyde. It has a significant role for example in epigenetic regulation. The whole methyl-pool can be evaluated by the measurement of bound formaldehyde. AIM: The bound formaldehyde was measured in wheat, bean, beetroot, cabbage, broiler- and rabbit liver. The relationship between transmethylation and redox homeosthasis was studied in the liver of domestic animals, and in the rat model of fatty liver. METHOD: The diet of rats was enriched with cholesterol, sunflower oil and cholic acid. The bound formaldehyde was determined by overpressured layer chromatography. The hydrogen-donating ability was measured with 1.1-diphenyl-2-picrylhydrazylt free radical using spectrophotometric measurement. RESULTS: Beans had the most bound formaldehyde. The liver of broilers possessed significantly elevated hydrogen-donating ability and transmethylation ability. Rats with severe fatty liver had significantly less bound formaldehyde and the hydrogen-donating ability tendentiously decreased. CONCLUSIONS: These results draw attention to the diet, especially in obesity and obesity-related diseases.


Assuntos
Beta vulgaris/metabolismo , Brassica/metabolismo , Fabaceae/metabolismo , Fígado Gorduroso/metabolismo , Formaldeído/metabolismo , Metilação , Metiltransferases/metabolismo , Oxirredução , Animais , Galinhas/metabolismo , Cromatografia Líquida de Alta Pressão , Metilação de DNA , Homeostase , Masculino , Obesidade/metabolismo , Prótons , Coelhos , Ratos , Ratos Wistar , Índice de Gravidade de Doença
8.
BMC Complement Altern Med ; 13: 152, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23815892

RESUMO

BACKGROUND: Formaldehyde can induce misfolding and aggregation of Tau protein and ß amyloid protein, which are characteristic pathological features of Alzheimer's disease (AD). An increase in endogenous formaldehyde concentration in the brain is closely related to dementia in aging people. Therefore, the discovery of effective drugs to counteract the adverse impact of formaldehyde on neuronal cells is beneficial for the development of appropriate treatments for age-associated cognitive decline. METHODS: In this study, we assessed the neuroprotective properties of TongLuoJiuNao (TLJN), a traditional Chinese medicine preparation, against formaldehyde stress in human neuroblastoma cells (SH-SY5Y cell line). The effect of TLJN and its main ingredients (geniposide and ginsenoside Rg1) on cell viability, apoptosis, intracellular antioxidant activity and the expression of apoptotic-related genes in the presence of formaldehyde were monitored. RESULTS: Cell counting studies showed that in the presence of TLJN, the viability of formaldehyde-treated SH-SY5Y cells significantly recovered. Laser scanning confocal microscopy revealed that the morphology of formaldehyde-injured cells was rescued by TLJN and geniposide, an effective ingredient of TLJN. Moreover, the inhibitory effect of geniposide on formaldehyde-induced apoptosis was dose-dependent. The activity of intracellular antioxidants (superoxide dismutase and glutathione peroxidase) increased, as did mRNA and protein levels of the antiapoptotic gene Bcl-2 after the addition of geniposide. In contrast, the expression of the apoptotic-related gene - P53, apoptotic executer - caspase 3 and apoptotic initiator - caspase 9 were downregulated after geniposide treatment. CONCLUSIONS: Our results indicate that geniposide can protect SH-SY5Y cells against formaldehyde stress through modulating the expression of Bcl-2, P53, caspase 3 and caspase 9, and by increasing the activity of intracellular superoxide dismutase and glutathione peroxidase.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Formaldeído/metabolismo , Iridoides/farmacologia , Neuroblastoma/metabolismo , Fármacos Neuroprotetores/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Tumoral , Humanos , Neuroblastoma/genética , Neuroblastoma/fisiopatologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 37(20): 3017-20, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23311145

RESUMO

The injury of exogenous formaldehyde and its merchanism have attracted wide attention from researchers. The latest study found that mammals have a whole system for generating and clearning formaldehyde. However, the imbalance on the system for generating and clearning formaldehyde for various reasons will cause abnormal accumulation of endogenous formaldehyde in vivo, which is closely related to learning diability and memory dysfunction. The increase in endogenous formaldehyde concentration may be one of factors inducing such neurodegenerative diseases as Alzheimer's disease. The study on the relationship between endogenous formaldehyde and such neurodegenerative diseases as Alzheimer's disease is of great significance and can provide new thoughts for preventing and treating Alzheimer's disease with traditional Chinese medicines.


Assuntos
Doença de Alzheimer/metabolismo , Formaldeído/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos
10.
Methods Mol Biol ; 659: 51-70, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20809303

RESUMO

Formalin fixed paraffin embedded (FFPE) material is frequently the most convenient readily available source of diseased tissue, including tumors. Multiple cores of FFPE material are being used increasingly to construct tissue microarrays (TMAs) that enable simultaneous analyses of many archival samples. Fluorescence in situ hybridization (FISH) is an important approach to analyze FFPE material for specific genetic aberrations that may be associated with tumor types or subtypes, cellular morphology, and disease prognosis. Annealing, or hybridization of labeled nucleic acid sequences, or probes, to detect and locate one or more complementary nucleic acid sequences within fixed tissue sections allows the detection of structural (translocation/inversion) and numerical (deletion/gain) aberrations and their localization within tissues. The robust protocols described include probe preparation, hybridization, and detection and take 2-3 days to complete. A protocol is also described for the stripping of probes for repeat FISH in order to maximize the use of scarce tissue resources.


Assuntos
Formaldeído/metabolismo , Hibridização in Situ Fluorescente/métodos , Inclusão em Parafina/métodos , Análise Serial de Tecidos/métodos , Fixação de Tecidos/métodos , Biotina/metabolismo , DNA/genética , DNA/metabolismo , Sondas de DNA/genética , Sondas de DNA/isolamento & purificação , Digoxigenina/metabolismo , Dosagem de Genes , Genômica , Humanos , Processamento de Imagem Assistida por Computador , Técnicas de Amplificação de Ácido Nucleico
11.
Plant Physiol Biochem ; 48(9): 787-96, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20650643

RESUMO

Solanum torvum is reported to carry resistance to bacterial wilt caused by Ralstonia solanacearum. So, this wild species is used as rootskock for eggplants or tomatoes in naturally infected soil. This study aimed to investigate the involvement of the polyamine metabolism pathway in the resistance mechanisms of this species. Calli induced from Solanum torvum stem explants were inoculated with the bacteria under partial vacuum. All calli showed a hypersensitive response after infiltration. Furthermore, amine oxidase activity with aldehyde and H(2)O(2) production was detected in soluble protein extracts of calli infiltrated by the bacteria. Due to its preferential affinity for aliphatic amines, this enzyme was supposed to have amine oxidase-like (AO-like) activity. Moreover, the length of aliphatic chain cycle altered the oxidative deamination kinetics of potential substrates. The AO-like catalytic activity was significantly inhibited by chelator agents such as ethylene-diamine-tretraacetic (EDTA), and also by semi-carbazide as aminoguanidine. These results suggested that (i) the prosthetic group of the AO-like enzyme could be a tyrosine-derived 6-hydroxytopaquinone structure, copper containing; (ii) this enzyme could be a semi-carbazide sensitive amine oxidase (SSAO).


Assuntos
Amina Oxidase (contendo Cobre)/metabolismo , Proteínas de Plantas/metabolismo , Caules de Planta/microbiologia , Ralstonia solanacearum/fisiologia , Solanum/microbiologia , Amina Oxidase (contendo Cobre)/química , Aminas/metabolismo , Biocatálise/efeitos dos fármacos , Quelantes/farmacologia , Ácido Edético/farmacologia , Formaldeído/metabolismo , Guanidinas/farmacologia , Interações Hospedeiro-Patógeno , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Proteínas de Plantas/química , Caules de Planta/enzimologia , Caules de Planta/metabolismo , Poliaminas/metabolismo , Solanum/enzimologia , Solanum/metabolismo , Solubilidade , Especificidade por Substrato , Técnicas de Cultura de Tecidos
12.
Acta Biol Hung ; 58(3): 301-10, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17899787

RESUMO

The effect of Se(IV) and Cu(II) ions on the antibacterial activity of aflatoxins and ochratoxin A (mycotoxins) was studied in BioArena as a complex bioautographic system. In the presence of 0.23 and 0.46 mg/100 mL Se(IV) the inhibition zones of mycotoxins were decreased, however, lower concentration (0.046 mg/100 mL) increased the antibacterial effect of aflatoxin B1. Cu(II) (1.53 mg/100 mL) enhanced the toxicity of mycotoxins. The results supported the possible role of formaldehyde and its reaction products (e.g. 1O2, O3) in the antibacterial-toxic action of mycotoxins. Cu(II) can probably generate and mobilise the formaldehyde molecules and so it could increase the toxicity with its potential reaction products. It is possible that the enzymatic or spontaneous methylation of Se(IV) takes place through formaldehyde, which may cause partial formaldehyde depletion in the system. The enhanced antibacterial effect at low concentration Se(IV) is overlapping with the often experienced prooxidant effect in cases of natural antioxidants.


Assuntos
Cobre/farmacologia , Micotoxinas/efeitos adversos , Pseudomonas/efeitos dos fármacos , Selênio/farmacologia , Aflatoxinas/efeitos adversos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Formaldeído/metabolismo , Ocratoxinas/efeitos adversos , Oxigênio/metabolismo , Pseudomonas/metabolismo
13.
Br J Cancer ; 96(11): 1667-74, 2007 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-17473824

RESUMO

Formaldehyde has been previously shown to play a dominant role in promoting synergy between doxorubicin (Dox) and formaldehyde-releasing butyric acid (BA) prodrugs in killing cancer cells. In this work, we report that these prodrugs also protect neonatal rat cardiomyocytes and adult mice against toxicity elicited by Dox. In cardiomyocytes treated with Dox, the formaldehyde releasing prodrugs butyroyloxymethyl diethylphosphate (AN-7) and butyroyloxymethyl butyrate (AN-1), but not the corresponding acetaldehyde-releasing butyroyloxydiethyl phosphate (AN-88) or butyroyloxyethyl butyrate (AN-11), reduced lactate dehydrogenase leakage, prevented loss of mitochondrial membrane potential (DeltaPsim) and attenuated upregulation of the proapoptotic gene Bax. In Dox-treated mice, AN-7 but not AN-88 attenuated weight-loss and mortality, and increase in serum lactate dehydrogenase. These findings show that BA prodrugs that release formaldehyde and augment Dox anticancer activity also protect against Dox cardiotoxicity. Based on these observations, clinical applications of these prodrugs for patients treated with Dox warrant further investigation.


Assuntos
Antineoplásicos/toxicidade , Ácido Butírico/farmacologia , Citoproteção/efeitos dos fármacos , Doxorrubicina/toxicidade , Formaldeído/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Organofosfatos/farmacologia , Pró-Fármacos/farmacologia , Animais , Animais Recém-Nascidos , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Butiratos , Ácido Butírico/metabolismo , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Feminino , Formaldeído/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Histona Desacetilases/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Miócitos Cardíacos/metabolismo , Compostos Organofosforados , Ratos
14.
Bioresour Technol ; 98(17): 3354-66, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17451946

RESUMO

The aim of the work described here was to analyse the biomethanization process for three types of organic fraction of municipal solid waste (OFMSW) using two different inoculum sources in a sequential leach-bed anaerobic reactor under thermophilic (55 degrees C) and dry conditions (20%TS). The OFMSWs studied were: separately collected food waste (SC_OFMSW) from restaurants, synthetic waste (ST_OFMSW) and mechanically selected municipal waste (MS_OFMSW). The inoculum studied were digested mesophilic sludge (SLUDGE) and digested SC_OFMSW. The results show that SLUDGE gave the best performance and this was therefore selected for the rest of the experiments. Three assays were performed to analyse the biomethanization processes of three types of organic waste. The results suggest that all three wastes give rise to an acclimation stage with acidogenic/acetogenic activity between days 5 and 20-30 and a stabilization phase associated with methanogenic activity. In conclusion, a mixture of OFMSW (regardless of its origin) and SWINE arranged in layers in the reactor, as well as SLUDGE used with an inoculum source, enhanced the fast start up phase of a modified sequential leach-bed system under dry thermophilic conditions.


Assuntos
Eliminação de Resíduos/métodos , Solo , Anaerobiose , Animais , Reatores Biológicos , Cidades , Alimentos , Formaldeído/metabolismo , Esgotos , Microbiologia do Solo , Suínos , Fatores de Tempo
15.
Acta Biochim Pol ; 53(3): 463-73, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17019438

RESUMO

A yeast isolate revealing unique enzymatic activities and substrate-dependent polymorphism was obtained from autochthonous microflora of soil heavily polluted with oily slurries. By means of standard yeast identification procedures the strain was identified as Trichosporon cutaneum. Further molecular PCR product analyses of ribosomal DNA confirmed the identity of the isolate with the genus Trichosporon. As it grew on methanol as a sole carbon source, the strain appeared to be methylotrophic. Furthermore, it was also able to utilize formaldehyde. A multi-substrate growth potential was shown with several other carbon sources: glucose, glycerol, ethanol as well as petroleum derivatives and phenol. Optimum growth temperature was determined at 25 degrees C, and strong inhibition of growth at 37 degrees C together with the original soil habitat indicated lack of pathogenicity in warm-blooded animals and humans. The unusually high tolerance to xenobiotics such as diesel oil (>30 g/l), methanol (50 g/l), phenol (2 g/l) and formaldehyde (7.5 g/l) proved that the isolate was an extremophilic organism. With high-density cultures, formaldehyde was totally removed at initial concentrations up to 7.5 g/l within 24 h, which is the highest biodegradation capability ever reported. Partial biodegradation of methanol (13 g/l) and diesel fuel (20 g/l) was also observed. Enzymatic studies revealed atypical methylotrophic pathway reactions, lacking alcohol oxidase, as compared with the conventional methylotroph Hansenula polymorpha. However, the activities of glutathione-dependent formaldehyde dehydrogenase, formaldehyde reductase, formate dehydrogenase and unspecific aldehyde dehydrogenase(s) were present. An additional glutathione-dependent aldehyde dehydrogenase activity was also detected. Metabolic and biochemical characteristics of the isolated yeast open up new possibilities for environmental biotechnology. Some potential applications in soil bioremediation and wastewater decontamination are discussed.


Assuntos
Microbiologia do Solo , Trichosporon/isolamento & purificação , Trichosporon/fisiologia , Eliminação de Resíduos Líquidos , Biodegradação Ambiental , Biotecnologia/métodos , Formaldeído/metabolismo , Gasolina/microbiologia , Metanol/metabolismo , Petróleo/metabolismo , Fenol/metabolismo , Polônia , Poluentes do Solo/química , Temperatura
16.
Mol Microbiol ; 60(4): 925-38, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16677304

RESUMO

To investigate Saccharomyces cerevisiae physiology during growth on the conditionally toxic triose dihydroxyacetone (DHA), protein expression was studied in strains overexpressing either of the two dihydroxyacetone kinase isogenes, DAK1 or DAK2, that grow well utilizing DHA as a carbon and energy source. DHA metabolism was found mostly similar to ethanol utilization, involving a strong component of glucose derepression, but also involved DHA-specific regulatory changes. A specific and strong (10- to 30-fold induction of formaldehyde dehydrogenase, Fdhlp, indicated activation of the formaldehyde dissimilation pathway in DHA medium. The importance of this pathway was further supported by impaired adaptation to DHA growth and DHA survival in a glutathione-dependent formaldehyde dehydrogenase (SFA1) deletion mutant. Glutathione synthase (GSH1) deletion led to decreased DHA survival in agreement with the glutathione cofactor requirement for the SFA1-encoded activity. DHA toxicity did, however, not solely appear related to formaldehyde accumulation, because SFA1 overexpression only enhanced formaldehyde but not DHA tolerance. In further agreement with a low DHA-to-formaldehyde flux, GSH supplements in the low microM range also fully suppressed the DHA sensitivity of a gsh1Delta strain. Under growth reduction on high (100 mM) DHA medium we report increased levels of advanced glycation end-product (AGE) formation on total protein. Under these high-DHA conditions expression of several stress-related proteins, e.g. a heat-shock protein (Hsp104p) and the oxidative stress indicator, alkyl hydroperoxide reductase (Ahp1p) was also found induced. However, hallmark determinants of oxidative stress tolerance (e.g. YAP1, SKN7, HYR1/GPX3 and SOD2) were redundant for DHA tolerance, thus indicating mechanisms of DHA toxicity largely independent of central oxidative stress defence mechanisms. We conclude that mechanisms for DHA growth and detoxification appear complex and that the evolutionary strive to minimize detrimental effects of this intracellular metabolite links to both formaldehyde and glutathione metabolism.


Assuntos
Di-Hidroxiacetona/metabolismo , Formaldeído/metabolismo , Formiato Desidrogenases/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Di-Hidroxiacetona/toxicidade , Etanol/metabolismo , Formiato Desidrogenases/genética , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Inativação Metabólica , Estresse Oxidativo/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteômica , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Deleção de Sequência , Ativação Transcricional , Regulação para Cima
17.
Acta Biol Hung ; 56(1-2): 21-34, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15813211

RESUMO

The aim of this study was to examine the antinociceptive potential of leaves of Ixora coccinea (family: Rubeaceae). One of four doses (500, 750, 1000 or 1500 mg/kg, n = 8/dose) of aqueous leaf extract (ALE) or 1 ml of distilled water was orally administered to male rats and antinociceptive activity was ascertained using three models ofnociception (tail flick, hot plate and formalin tests). The results showed that ALE possesses considerable antinociceptive activity (when evaluated in hot plate and formalin test but not in tail flick test). The antinociceptive activity of the ALE had a rapid onset (within 1h) and a fairly long duration of action (up to 5 h) with a peak effect at 3 h. Further, the antinociceptive activity was dose-dependent and was not associated with harmful side-effects or toxicity even following subchronic administration. The antinociceptive action was mediated centrally at the supraspinal level mainly via dopaminergic mechanism. In addition, it is likely that antioxidant activity of the ALE could have played an auxiliary role in inducing antinociception. Dopaminergic and antioxidative activities of ALE could arise, respectively, from its quaternary base alkaloid and flavonoid constituents.


Assuntos
Analgésicos/farmacologia , Extratos Vegetais , Folhas de Planta/metabolismo , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/sangue , Membrana Celular/metabolismo , Creatinina/sangue , Dopamina/metabolismo , Feminino , Fertilidade/efeitos dos fármacos , Formaldeído/metabolismo , Temperatura Alta , Masculino , Músculos/efeitos dos fármacos , Músculos/metabolismo , Dor , Prostaglandinas/biossíntese , Prostaglandinas/metabolismo , Distribuição Aleatória , Ratos , Receptores Dopaminérgicos/metabolismo , Receptores Opioides/metabolismo , Fatores de Tempo , Ureia/metabolismo , Água/metabolismo
18.
Bioresour Technol ; 96(1): 95-101, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15364086

RESUMO

This work evaluates the feasibility of reacting tannins isolated from Pinus radiata D. Don bark with epoxide resins of the diglycidyl and polyglycidyl ether type. To this end, gel times of aqueous tannin dispersions (40% w/w) with every one of nine selected resins (5% w/w), at previously established pH values (initial equal to 3.3, 4, 7 and 10), have been determined. Products of these reactions were analyzed by FT-IR spectroscopy, and the results were compared with those obtained from tannin-p-formaldehyde and (+)-catechin-p-formaldehyde systems, at the same pH values. Their mechanical properties were evaluated, by dynamic mechanical analysis, at two pH values (3.3 and 10). In general, it was concluded that tannin-epoxide resin systems behave similarly to tannin-paraformaldehyde systems, especially at basic pH values.


Assuntos
Compostos de Epóxi/metabolismo , Pinus/química , Casca de Planta/química , Resinas Vegetais/metabolismo , Taninos/metabolismo , Catequina/metabolismo , Compostos de Epóxi/química , Compostos de Epóxi/isolamento & purificação , Formaldeído/metabolismo , Concentração de Íons de Hidrogênio , Extratos Vegetais/química , Resinas Vegetais/química , Resinas Vegetais/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier , Taninos/química , Taninos/isolamento & purificação , Temperatura , Fatores de Tempo
19.
Nephrology (Carlton) ; 9(2): 65-72, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15056264

RESUMO

BACKGROUND: Aldehydes were identified in clinical solutions, including peritoneal dialysis (PD) and cryoprotection solutions, which were used to freeze cells, tissues and embryos. Aldehydes are associated with increased cellular injury and may contribute to peritoneal membrane damage that occurs in patients on peritoneal dialysis. Recently, it was demonstrated that aldehydes could be 'scavenged' from these solutions by using aminothiol compounds. Although aldehydes were removed during the scavenging process, the kinetics of scavenging and the products formed were not characterized. METHODS: Proton nuclear magnetic resonance (NMR) spectroscopy was used to investigate formaldehyde scavenging from an artificial PD solution supplemented with aminothiol compounds, cysteamine or l-cysteine. Artificial PD solutions were formulated on the basis of commercial PD solutions and consisted of 132 mmol/L NaCl, 0.25 mmol/L MgCl2, 1.25 mmol/L CaCl2, and buffered with lactate (4.0 mmol/L) and lacked d-glucose. Formaldehyde scavenging was a two-step process involving an intermediate step followed by the formation of stable thiazolidine compounds. These included the derivatives of cysteamine and l-cysteine; thiazolidine and thiazolidine-4-carboxylic acid, respectively. CONCLUSION: Scavenging with aminothiol compounds masked the destructive carbonyl group (C = O) of formaldehyde and formed a compound that has antioxidant properties. The addition of aminothiol compounds may improve the biocompatibility of commercial PD solutions.


Assuntos
Cisteamina/metabolismo , Cisteína/metabolismo , Soluções para Diálise , Formaldeído/metabolismo , Diálise Peritoneal , Espectroscopia de Ressonância Magnética
20.
Can J Microbiol ; 50(2): 91-6, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15052310

RESUMO

The in situ degradation of the two nitramine explosives, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), was evaluated using a mixture of RDX and HMX, incubated anaerobically at 10 degrees C with marine sediment from a previous military dumping site of unexploded ordnance (UXO) in Halifax Harbor, Nova Scotia, Canada. The RDX concentration (14.7 mg.L-1) in the aqueous phase was reduced by half in 4 days, while reduction of HMX concentration (1.2 mg.L-1) by half required 50 days. Supplementation with the carbon sources glucose, acetate, or citrate did not affect the removal rate of RDX but improved removal of HMX. Optimal mineralization of RDX and HMX was obtained in the presence of glucose. Using universally labeled (UL)-[14C]RDX, we obtained a carbon mass balance distributed as follows: CO2, 48%-58%; water soluble products, 27%-31%; acetonitrile extractable products, 2.0%-3.4%; and products covalently bound to the sediments and biomass, 8.9% (in the presence of glucose). The disappearance of RDX was accompanied by the formation of the mononitroso derivative hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and formaldehyde (HCHO) that subsequently disappeared. In the case of HMX, mineralization reached only 13%-27% after 115 days of incubation in the presence or absence of the carbon sources. The disappearance of HMX was also accompanied by the formation of the mononitroso derivative. The total population of psychrotrophic anaerobes that grew at 10 degrees C was 2.6 x 10(3) colony-forming units.(g sediment dry mass)-1, and some psychrotrophic sediment isolates were capable of degrading RDX under conditions similar to those used for sediments. Based on the distribution of products, we suggest that the sediment microorganisms degrade RDX and HMX via an initial reduction to the corresponding mononitroso derivative, followed by denitration and ring cleavage.


Assuntos
Azocinas/metabolismo , Bactérias/metabolismo , Sedimentos Geológicos/microbiologia , Compostos Heterocíclicos com 1 Anel/metabolismo , Triazinas/metabolismo , Acetatos/metabolismo , Anaerobiose , Biodegradação Ambiental , Radioisótopos de Carbono , Citratos/metabolismo , Contagem de Colônia Microbiana , Formaldeído/química , Formaldeído/metabolismo , Glucose/metabolismo , Cinética , Compostos Nitrosos/química , Compostos Nitrosos/metabolismo , Temperatura
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