Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.292
Filtrar
1.
Chemosphere ; 241: 125099, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629238

RESUMO

Our previous study showed that excessive fluoride (F) intake can induce liver dysfunction. The aim of this study was to investigate the mechanisms of F-induced mitochondrial damage resulting in liver dysfunction. Damaged mitochondrial ultrastructure and state of liver cells were estimated by TEM, TUNEL staining and BrdU measurement. The ROS level and ATP content in the liver tissue were measured by ELISA kit. Meanwhile, optic atrophy (OPA1), mitofusin-1 (Mfn1), NDUFV2, SDHA, CYC1, and COX Ⅳ expression levels were measured through real-time PCR and Western-blot. Results showed that the ROS level increased, thereby resulting in mitochondrial ultrastructure damage and abundant liver cells presented evident apoptotic characteristics after F treatment. Decreased ATP content and the abnormal expression of OPA1, Mfn1, NDUFV2, SDHA, CYC1, and COX Ⅳ of the liver tissue were observed. In conclusion, excessive F-induced mitochondrial respiratory chain damaged and mitochondrial fusion disorder resulted in liver dysfunction.


Assuntos
Transporte de Elétrons/efeitos dos fármacos , Fluoretos/toxicidade , Hepatopatias/etiologia , Dinâmica Mitocondrial/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatopatias/genética , Hepatopatias/metabolismo , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo
2.
Biochim Biophys Acta Bioenerg ; 1861(2): 148134, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31825806

RESUMO

Cytochrome b5 reductase is an enzyme with the ability to generate superoxide anion at the expenses of NADH consumption. Although this activity can be stimulated by cytochrome c and could participate in the bioenergetic failure accounting in apoptosis, very little is known about other molecules that may uncouple the function of the cytochrome b5 reductase. Naphthoquinones are redox active molecules with the ability to interact with electron transfer chains. In this work, we made an inhibitor screening against recombinant human cytochrome b5 reductase based on naphthoquinone properties. We found that 5-hydroxy-1,4-naphthoquinone (known as juglone), a natural naphthoquinone extracted from walnut trees and used historically in traditional medicine with ambiguous health and toxic outcomes, had the ability to uncouple the electron transfer from the reductase to cytochrome b5 and ferricyanide. Upon complex formation with cytochrome b5 reductase, juglone is able to act as an electron acceptor leading to a NADH consumption stimulation and an increase of superoxide anion production by the reductase. Our results suggest that cytochrome b5 reductase could contribute to the measured energetic failure in the erythrocyte apoptosis induced by juglone, that is concomitant with the reactive oxygen species produced by cytochrome b5 reductase.


Assuntos
Citocromo-B(5) Redutase/metabolismo , Eritrócitos/metabolismo , Naftoquinonas/farmacologia , Superóxidos/metabolismo , Apoptose/efeitos dos fármacos , Citocromos b5/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Humanos , NAD/metabolismo
3.
Aquat Toxicol ; 217: 105349, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31734626

RESUMO

Ocean acidification, due to increased levels of anthropogenic carbon dioxide, is known to affect the physiology and growth of marine phytoplankton, especially in polar regions. However, the effect of acidification or carbonation on cellular metabolism in polar marine phytoplankton still remains an open question. There is some evidence that small chlorophytes may benefit more than other taxa of phytoplankton. To understand further how green polar picoplankton could acclimate to high oceanic CO2, studies were conducted on an Antarctic Chlorella sp. Chlorella sp. maintained its growth rate (∼0.180 d-1), photosynthetic quantum yield (Fv/Fm = ∼0.69) and chlorophyll a (0.145 fg cell-1) and carotenoid (0.06 fg cell-1) contents under high CO2, while maximum rates of electron transport decreased and non-photochemical quenching increased under elevated CO2. GCMS-based metabolomic analysis reveal that this polar Chlorella strain modulated the levels of metabolites associated with energy, amino acid, fatty acid and carbohydrate production, which could favour its survival in an increasingly acidified ocean.


Assuntos
Chlorella/metabolismo , Metaboloma/efeitos dos fármacos , Microalgas/metabolismo , Água do Mar/química , Aclimatação/efeitos dos fármacos , Aminoácidos/biossíntese , Regiões Antárticas , Dióxido de Carbono/análise , Dióxido de Carbono/toxicidade , Chlorella/efeitos dos fármacos , Clorofila A/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Ácidos Graxos/biossíntese , Concentração de Íons de Hidrogênio , Metabolômica , Microalgas/efeitos dos fármacos , Oceanos e Mares , Fotossíntese/efeitos dos fármacos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
4.
Aquat Toxicol ; 216: 105295, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561136

RESUMO

Oxybenzone (OBZ; benzophenone-3, CAS# 131-57-7) is a known pollutant of aquatic and marine ecosystems, and is an ingredient in over 3000 personal care products, as well as many types of plastics. The aim of this study is to explore the different toxicities of OBZ on an eukaryotic (Chlorella sp.) and a prokaryotic algae (Arthrospira sp.). OBZ is a photo-toxicant, with all observed toxicities more sever in the light than in the dark. Cell growth and chlorophyll inhibition were positively correlated with increasing OBZ concentrations over time. Twenty days treatment with OBZ, as low as 22.8 ng L-1, significantly inhibited the growth and chlorophyll synthesis of both algae. Both algae were noticeably photo-bleached after 7 days of exposure to OBZ concentrations higher than 2.28 mg L-1. Relatively low OBZ concentrations (0.228 mg L-1) statistically constrained photosynthetic and respiratory rates via directly inhibiting photosynthetic electron transport (PET) and respiration electron transport (RET) mechanisms, resulting in over production of reactive oxygen species (ROS). Transmission and scanning electron microscopy showed that the photosynthetic and respiratory membrane structures were damaged by OBZ exposure in both algae. Additionally, PET inhibition suppressed ATP production for CO2 assimilation via the Calvin-Benson cycle, further limiting synthesis of other biomacromolecules. RET restriction limited ATP generation, restricting the energy supply used for various life activities in the cell. These processes further impacted on photosynthesis, respiration and algal growth, representing secondary OBZ-induced algal damages. The data contained herein, as well as other studies, supports the argument that global pelagic and aquatic phytoplankton could be negatively influenced by OBZ pollution.


Assuntos
Benzofenonas/toxicidade , Chlorella/efeitos dos fármacos , Cosméticos/toxicidade , Spirulina/efeitos dos fármacos , Protetores Solares/toxicidade , Trifosfato de Adenosina/metabolismo , Respiração Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Chlorella/crescimento & desenvolvimento , Chlorella/ultraestrutura , Clorofila/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Luz , Fotossíntese/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Spirulina/crescimento & desenvolvimento , Spirulina/ultraestrutura , Fatores de Tempo , Poluentes Químicos da Água/toxicidade
5.
Mol Med Rep ; 20(5): 4383-4390, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545457

RESUMO

Volatile anesthetics may protect the heart against ischemia­reperfusion injury via the direct action on mitochondrial complexes and by regulating the production of reactive oxygen species (ROS). Recently, we reported that isoflurane induced the attenuation of mitochondrial respiration caused by complex I substrates. This process was not associated with endogenous production of mitochondrial nitric oxide (NO). In the present study, we investigated the effects of isoflurane on mitochondrial respiration and ROS production using complex II substrates. The detailed mechanism of these effects was explored with regards to NO production and the expression of mitochondrial ATP­dependent K+ (mKATP) channels. Mitochondria were isolated from the heart of Sprague­Dawley rats. The respiratory rates of mitochondria (0.5 mg/ml) were measured via polarography at 28˚C with computer­controlled Clark­type O2 electrodes. The complex II substrate succinate (5 mM) was used; 0.25 mM of isoflurane was administered prior to ADP­initiated state 3 respiration. The mitochondrial membrane potential (ΔΨm) was measured under treatment with the substrate succinate, or succinate in the presence of the complex I inhibitor rotenone. The detection was achieved in a cuvette­based spectrophotometer operating at wavelengths of 503 nm (excitation) 527 nm (emission) in the presence of 50 nM of the fluorescent dye rhodamine 123. The H2O2 release rates in the mitochondria were measured spectrophotometrically with succinate, or succinate and rotenone using the fluorescent dye Amplex red (12.5­25 µM). The results indicated that isoflurane increased the state 3 and 4 respiration rates caused by succinate, which were higher than those noted in the control group in the presence of succinate alone. The NOS inhibitor L­NIO or the NO­sensitive guanylyl cyclase 1H­[1,2,4]oxadiazolo[4,3­a]quinoxalin­1­one did not inhibit the increase in the respiration rate (state 3) induced by isoflurane. The ROS scavengers SPBN and manganese (III) tetrakis (4­benzoic acid) porphyrin chloride inhibited the increase in the respiration rate (state 3 and 4) induced by isoflurane. This effect was not noted for the putative KATP channel blockers 5­hydroxydecanoic acid and glibenclamide. Isoflurane caused a greater decrease in the concentration of H2O2 during ADP­initiated state 3 respiration, and L­N5­(1­Iminoethyl)­ornithine did not inhibit this effect. In conclusion, isoflurane was determined to modulate mitochondrial respiration and ROS production caused by the complex II substrate succinate. These effects were independent of endogenous mitochondrial NO generation and mitochondrial KATP channel opening.


Assuntos
Respiração Celular/efeitos dos fármacos , Complexo II de Transporte de Elétrons/metabolismo , Isoflurano/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Transporte de Elétrons/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/genética , Óxido Nítrico/metabolismo , Consumo de Oxigênio , Canais de Potássio/metabolismo , Ratos
6.
Aquat Toxicol ; 214: 105258, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31374405

RESUMO

A vast variety of substances currently reaches the aquatic environment, including newly developed chemicals and products. Lack of appropriate analytical methods for trace determinations in aquatic ecosystem compartments and lack of information regarding their toxicity explains existing regulation gaps. However, suspicion of their toxicity assigned them as Contaminants of Emerging Concern (CECs). Among CECs are Pharmaceuticals including Salicylic Acid (SA), which is the active metabolite of acetylsalicylic acid (ASA; aspirin). The aim of the present study was to evaluate the potential effects of SA on the mussel Mytilus galloprovincialis. For this, organisms were exposed for 28 days to different concentrations of SA (0.005; 0.05; 0.5 and 5 mg/L), resembling low to highly polluted sites, after which different physiological and biochemical parameters were evaluated to assess organism's respiration rate, neurotoxic, metabolic and oxidative stress status. Our results clearly showed that SA strongly reduced the respiration capacity of mussels. Also, SA inhibited the activity of superoxide dismutase (SOD) and catalase (CAT) enzymes, but increased the activity of glutathione peroxidase (GPx) and glutathione-S-transferases (GSTs), which prevented the occurrence of lipid peroxidation (LPO). Nevertheless, oxidative stress was confirmed by the strong decrease of the ratio between reduce glutathione (GSH) and oxidized (GSSG) glutathione in contaminated mussels. Moreover, neurotoxicity was observed in mussels exposed to SA. Overall, this study demonstrates the metabolic, neurotoxic and oxidative stress impacts of SA in M. galloprovincialis, which may result in negative consequences at the population level.


Assuntos
Mytilus/fisiologia , Ácido Salicílico/efeitos adversos , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Biotransformação , Catalase/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Mytilus/efeitos dos fármacos , Neurotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Respiração , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/toxicidade
7.
Molecules ; 24(16)2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31426567

RESUMO

A series of twenty-six methoxylated and methylated N-aryl-1-hydroxynaphthalene- 2-carboxanilides was prepared and characterized as potential anti-invasive agents. The molecular structure of N-(2,5-dimethylphenyl)-1-hydroxynaphthalene-2-carboxamide as a model compound was determined by single-crystal X-ray diffraction. All the analysed compounds were tested against the reference strain Staphylococcus aureus and three clinical isolates of methicillin-resistant S. aureus as well as against Mycobacterium tuberculosis and M. kansasii. In addition, the inhibitory profile of photosynthetic electron transport in spinach (Spinacia oleracea L.) chloroplasts was specified. In vitro cytotoxicity of the most effective compounds was tested on the human monocytic leukaemia THP-1 cell line. The activities of N-(3,5-dimethylphenyl)-, N-(3-fluoro-5-methoxy-phenyl)- and N-(3,5-dimethoxyphenyl)-1-hydroxynaphthalene-2-carbox- amide were comparable with or even better than the commonly used standards ampicillin and isoniazid. All promising compounds did not show any cytotoxic effect at the concentration >30 µM. Moreover, an in silico evaluation of clogP features was performed for the entire set of the carboxamides using a range of software lipophilicity predictors, and cross-comparison with the experimentally determined lipophilicity (log k), in consensus lipophilicity estimation, was conducted as well. Principal component analysis was employed to illustrate noticeable variations with respect to the molecular lipophilicity (theoretical/experimental) and rule-of-five violations. Additionally, ligand-oriented studies for the assessment of the three-dimensional quantitative structure-activity relationship profile were carried out with the comparative molecular surface analysis to determine electron and/or steric factors that potentially contribute to the biological activities of the investigated compounds.


Assuntos
Anilidas/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mycobacterium kansasii/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Naftóis/farmacologia , Ampicilina/farmacologia , Anilidas/síntese química , Anilidas/química , Antibacterianos/síntese química , Antibacterianos/química , Cloroplastos/efeitos dos fármacos , Cloroplastos/fisiologia , Transporte de Elétrons/efeitos dos fármacos , Humanos , Isoniazida/farmacologia , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Metilação , Testes de Sensibilidade Microbiana , Mycobacterium kansasii/crescimento & desenvolvimento , Mycobacterium tuberculosis/crescimento & desenvolvimento , Naftóis/síntese química , Naftóis/química , Fotossíntese/efeitos dos fármacos , Análise de Componente Principal , Spinacia oleracea/química , Spinacia oleracea/efeitos dos fármacos , Spinacia oleracea/metabolismo , Relação Estrutura-Atividade , Células THP-1
8.
Nat Rev Endocrinol ; 15(10): 569-589, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31439934

RESUMO

Despite its position as the first-line drug for treatment of type 2 diabetes mellitus, the mechanisms underlying the plasma glucose level-lowering effects of metformin (1,1-dimethylbiguanide) still remain incompletely understood. Metformin is thought to exert its primary antidiabetic action through the suppression of hepatic glucose production. In addition, the discovery that metformin inhibits the mitochondrial respiratory chain complex 1 has placed energy metabolism and activation of AMP-activated protein kinase (AMPK) at the centre of its proposed mechanism of action. However, the role of AMPK has been challenged and might only account for indirect changes in hepatic insulin sensitivity. Various mechanisms involving alterations in cellular energy charge, AMP-mediated inhibition of adenylate cyclase or fructose-1,6-bisphosphatase 1 and modulation of the cellular redox state through direct inhibition of mitochondrial glycerol-3-phosphate dehydrogenase have been proposed for the acute inhibition of gluconeogenesis by metformin. Emerging evidence suggests that metformin could improve obesity-induced meta-inflammation via direct and indirect effects on tissue-resident immune cells in metabolic organs (that is, adipose tissue, the gastrointestinal tract and the liver). Furthermore, the gastrointestinal tract also has a major role in metformin action through modulation of glucose-lowering hormone glucagon-like peptide 1 and the intestinal bile acid pool and alterations in gut microbiota composition.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Transporte de Elétrons/efeitos dos fármacos , Transporte de Elétrons/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Glucose/antagonistas & inibidores , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia
9.
Molecules ; 24(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426298

RESUMO

Amongst the various approaches to contain aflatoxin contamination of feed and food commodities, the use of inhibitors of fungal growth and/or toxin biosynthesis is showing great promise for the implementation or the replacement of conventional pesticide-based strategies. Several inhibition mechanisms were found taking place at different levels in the biology of the aflatoxin-producing fungal species such as Aspergillus flavus: compounds that influence aflatoxin production may block the biosynthetic pathway through the direct control of genes belonging to the aflatoxin gene cluster, or interfere with one or more of the several steps involved in the aflatoxin metabolism upstream. Recent findings pointed to mitochondrial functionality as one of the potential targets of some aflatoxin inhibitors. Additionally, we have recently reported that the effect of a compound belonging to the class of thiosemicarbazones might be related to the energy generation/carbon flow and redox homeostasis control by the fungal cell. Here, we report our investigation about a putative molecular target of the 3-isopropylbenzaldehyde thiosemicarbazone (mHtcum), using the yeast Saccharomyces cerevisiae as model system, to demonstrate how the compound can actually interfere with the mitochondrial respiratory chain.


Assuntos
Aflatoxinas/antagonistas & inibidores , Antifúngicos/farmacologia , Regulação Fúngica da Expressão Gênica , Mitocôndrias/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Tiossemicarbazonas/farmacologia , Aflatoxinas/biossíntese , Antifúngicos/química , Aspergillus flavus/efeitos dos fármacos , Aspergillus flavus/enzimologia , Aspergillus flavus/genética , Sítios de Ligação , Transporte de Elétrons/efeitos dos fármacos , Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo III da Cadeia de Transporte de Elétrons/química , Complexo III da Cadeia de Transporte de Elétrons/genética , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Mitocôndrias/metabolismo , Modelos Biológicos , Simulação de Acoplamento Molecular , Família Multigênica , Ligação Proteica , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Tiossemicarbazonas/química
10.
Chemosphere ; 233: 905-912, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31340418

RESUMO

We investigated the interconnected roles of reactive oxygen species (ROS) generated upon seed exposure to glyphosate and/or gibberellic acid (GA3), and the possible interaction between the herbicide and the plant hormone during germination of sorghum seeds. GA3 decreased antioxidant enzyme activity in embryos, and the over accumulation of hydrogen peroxide (H2O2) in 1000 mM GA3-treated seeds resulted in the lowest germinability among treatments. The deleterious effects of glyphosate on germination rate, in contrast, were not related to H2O2 accumulation, but to its interference with the mitochondrial electron transport chain. However, interactions among glyphosate, GA3 and H2O2 during seed germination were observed. Similar to paclobutrazol, glyphosate appears to interfere with the de novo synthesis of gibberellin, which modulates seed germination through oxidative metabolism. Seeds experiencing increased oxidative status due to GA3 (100 mM) or H2O2 (50 mM) applications had the effects of glyphosate on germination rate reversed. Since decreased ATP synthesis is a secondary effect of glyphosate, increased H2O2 concentrations in embryos must facilitate germination by decreasing the energy required by ATP-demanding metabolism. Our results showed that glyphosate affect seed germination of sorghum, and that the herbicide interacts with oxidative and gibberellin metabolisms.


Assuntos
Germinação/efeitos dos fármacos , Giberelinas/metabolismo , Glicina/análogos & derivados , Herbicidas/farmacologia , Peróxido de Hidrogênio/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Sorghum/metabolismo , Antioxidantes/metabolismo , Grão Comestível/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Glicina/farmacologia , Sementes/efeitos dos fármacos
11.
An Acad Bras Cienc ; 91(2): e20181373, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31241709

RESUMO

Fabry disease (FD) is an X-linked inherited disease and occurs due to mutations in GLA gene that encodes the α-galactosidase enzyme. Consequently, there is an accumulation of enzyme substrates, namely globotriaosylceramide (GB3). FD is a multisystemic disease, caused by storage of GB3 in vascular endothelia, with significant renal, cardiac and vascular involvement. The aim of this work was to evaluate the in vitro effect of GB3 on electron transport chain complexes (ETC) and redox parameters. Biochemical biomarkers were determined in homogenates of cerebral cortex, kidneys and liver of Wistar rats in the presence or absence of GB3 at concentrations of 3, 6, 9 and 12 mg/L. We found that GB3 caused an increase of ETC complexes II and IV activities, increased production of reactive species and decreased superoxide dismutase enzyme activity in homogenates of cerebral cortex. As well also increased production of reactive species and superoxide dismutase activity in kidney homogenates. The results obtained in our work suggest that GB3 interferes in ETC complexes II and IV activities, however, the magnitude of this increase seems to be too low to present a physiologically importance. However, the imbalance in cellular redox state indicating that these alterations may be involved in the pathophysiology of FD, mainly in renal and cerebral manifestations.


Assuntos
Córtex Cerebral/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Doença de Fabry/metabolismo , Rim/metabolismo , Fígado/metabolismo , Oxirredução/efeitos dos fármacos , Triexosilceramidas/farmacologia , Animais , Modelos Animais de Doenças , Doença de Fabry/enzimologia , Masculino , Ratos , Ratos Wistar
12.
Ecotoxicol Environ Saf ; 181: 146-154, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31177079

RESUMO

The impact of lead (Pb) on Spirodela polyrhiza was studied to determine the subcellular distribution, chemical forms, and resulting morphophysiological modifications after treatments with 20 or 80 µM Pb(NO3)2 for 10 days. At the subcellular level, the Pb uptake by S. polyrhiza was mainly compartmentalized in the cell walls (70%), and the majority of Pb (approximately 70%) was extracted using 1 M NaCl and 2% acetic acid (HAc). Visual symptoms of phytotoxcity, surface roughness and closure of stomata, were observed in Pb-treated fronds. Electron-dense precipitates were present in cell walls, and changes to the ultrastructure were most noticeably exhibited in organelle shape, internal organization, and size of the plastoglobules of chloroplasts. Toxic concentrations of Pb induced oxidative stress in fronds, characterized by an accumulation of malondialdehyde (MDA) and decreased chlorophyll and unsaturated fatty acid contents. Pb exposure increased ABS/RC, TRo/RC, DIo/RC, Vj, and φDo (Fv/Fm), indicating that reaction centers were transformed to dissipation sinks, leading to a decrease in the efficiency of photosystem II, which was evident from the decreased values of Fv/Fo, Fv/Fm, ψEo, φEo, RC/ABS, and PIabs. These results indicated that decreased photosynthesis in Pb-treated fronds was partially ascribed to the lower pigment content, inhibition of electron transport, inactivation of the reaction centers, damage to the chloroplast ultrastructure, and stomatal closure. The physiological implications of subcellular distribution and chemical forms are discussed in relation to Pb accumulation and detoxification. However, Pb accumulation significantly impaired photosynthesis and membrane integrity in the fronds of S. polyrhiza.


Assuntos
Araceae/efeitos dos fármacos , Chumbo/toxicidade , Araceae/anatomia & histologia , Araceae/metabolismo , Araceae/ultraestrutura , Clorofila/metabolismo , Cloroplastos/efeitos dos fármacos , Cloroplastos/ultraestrutura , Transporte de Elétrons/efeitos dos fármacos , Ácidos Graxos Insaturados/metabolismo , Chumbo/farmacocinética , Malondialdeído/metabolismo , Fotossíntese/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/metabolismo
13.
Microb Pathog ; 134: 103580, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31195112

RESUMO

Essential oils are a complex mixture of odoriferous, volatile organic compounds. There are an extensive number of published articles which highlight the antimicrobial action of a variety of essential oils from various parts of the world. The main aim of this review article is to compile these antimicrobial essential oils and their constituents from reliable sources and put them together. The published literature indicates that essential oils possess a wide-spectrum of antibacterial, antifungal and even anti-viral activity. Essential oils have also been shown to inhibit the growth of drug-resistant microbial strains which are even difficult to be treated by conventional antibiotics. As for as their mode of action is concerned, in fungal pathogens, essential oils establish a membrane potential across cell wall and disrupt ATP assembly, leading to cell wall damage. Essential oils can also disintegrate mitochondrial membrane interfering with the electron transport system (ETS) pathway. In bacterial pathogens, essential oils primarily destabilize the cellular architecture, leading to breakdown of membrane integrity, disrupting many cellular activities including energy production and membrane transport. Membrane rupture induced by essential oils can lead to leakage of cellular components and loss of ions. Several essential oils have antiviral activities against many RNA and DNA viruses, such as type 1 and type 2 herpes simplex virus (HSV-1 and HSV-2), dengue virus type 2, influenza virusadeno virus type 3, poliovirus, Junin virus, and coxsackievirus B1. In conclusion, the current review article discusses in detail the various aspects of antimicrobial activity of essential oils in a comprehensive manner.


Assuntos
Anti-Infecciosos/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Óleos Voláteis/farmacologia , Animais , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antivirais/farmacologia , Bactérias/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Farmacorresistência Viral , Transporte de Elétrons/efeitos dos fármacos , Fungos/efeitos dos fármacos , Humanos , Óleos Voláteis/química , Óleos Vegetais/farmacologia , Plantas/química , Percepção de Quorum/efeitos dos fármacos , Terpenos/farmacologia , Vírus/efeitos dos fármacos
14.
Nanoscale ; 11(22): 10791-10807, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31134256

RESUMO

Previously, our group reported on the promising efficacy of poly(ethylene glycol)-hydrophilic carbon clusters (PEG-HCCs) to work as broadly active and high capacity antioxidants in brain ischemia and injury models including stroke and traumatic brain injury coupled with hemorrhagic shock. PEG-HCCs are a carbon nanomaterial derived from harsh oxidation of single wall carbon nanotubes and covalently modified with poly(ethylene glycol). They retain no tubular remnants and are composed of a highly oxidized carbon core functionalized with epoxy, peroxyl, quinone, ketone, carboxylate, and hydroxyl groups. HCCs are the redox active carbon core of PEG-HCCs, which have a broad reduction potential range starting at +200 mV and extending to -2 V. Here we describe a new property of these materials: the ability to catalytically transfer electrons between key surrogates and proteins of the mitochondrial electron transport complex in a catalytic fashion consistent with the concept of a nanozyme. The estimated reduction potential of PEG-HCCs is similar to that of ubiquinone and they enabled the catalytic transfer of electrons from low reduction potential species to higher reduction electron transport complex constituents. PEG-HCCs accelerated the reduction of resazurin (a test indicator of mitochondrial viability) and cytochrome c by NADH and ascorbic acid in solution. Kinetic experiments suggested a transient tertiary complex. Electron paramagnetic resonance demonstrated NADH increased the magnitude of PEG-HCCs' intrinsic radical, which then reduced upon subsequent addition of cytochrome c or resazurin. Deconvolution microscopy identified PEG-HCCs in close proximity to mitochondria after brief incubation with cultured SHSY-5Y human neuroblastoma cells. Compared to methylene blue (MB), considered a prototypical small molecule electron transport shuttle, PEG-HCCs were more protective against toxic effects of hydrogen peroxide in vitro and did not demonstrate impaired cell viability as did MB. PEG-HCCs were protective in vitro when cells were exposed to sodium cyanide, a mitochondrial complex IV poison. Because mitochondria are a major source of free radicals in pathology, we suggest that this newly described nanozyme action helps explain their in vivo efficacy in a range of injury models. These findings may also extend their use to mitochondrial disorders.


Assuntos
Citocromos c/metabolismo , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/metabolismo , NAD/metabolismo , Nanotubos de Carbono/química , Ácido Ascórbico/farmacologia , Catálise , Espectroscopia de Ressonância de Spin Eletrônica , Transporte de Elétrons/efeitos dos fármacos , Humanos , Oxirredução/efeitos dos fármacos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia
15.
Photosynth Res ; 142(1): 57-67, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31098930

RESUMO

Effect of water-soluble and stable sucrose-bound iron oxyhydroxide nanoparticles [Fe[III] sucrose complex (FSC)] on the efficiency of electron transport in the photosystem II membranes was studied. FSC significantly increases (by a factor 1.5) the rate of light-induced oxygen evolution in the presence of alternative electron acceptor 2,6-dichloro-p-benzoquinone (DCBQ). Without DCBQ, FSC only slightly (5%) provides the oxygen evolution. Electron transport supported by pair DCBQ + FSC is inhibited by diuron. Maximum of stimulating effect was recorded at Fe(III) concentration 5 µM. In the case of another benzoquinone electron acceptor (2-phenyl-p-benzoquinone and 2,3-dimethyl-p-benzoquinone) and 2,6-dichlorophenolindophenol, stimulating effect of FSC was not observed. Incubation of PSII membranes at different concentrations with FSC is accompanied by binding of Fe(III) by membrane components but only about 50% of iron can be extracted by membranes from Fe(III) solution at pH 6.5. This result implies the heterogeneity of FSC solution in a buffer. The heterogeneity depends on pH and decreases with its rising. At pH around 9.0 Fe(III), sucrose solution is homogeneous. The study of pH effect has shown that stimulation of electron transport is induced only by iron cations which can be bound by membranes. Not extractable iron pool cannot activate electron transfer from oxygen-evolving complex to DCBQ.


Assuntos
Transporte de Elétrons/efeitos dos fármacos , Compostos Férricos/farmacologia , Nanopartículas/química , Oxigênio/metabolismo , Fotossíntese , Complexo de Proteína do Fotossistema II/efeitos dos fármacos , Solubilidade , Spinacia oleracea/metabolismo , Sacarose/química , Tilacoides/metabolismo
16.
Oxid Med Cell Longev ; 2019: 1583656, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31007832

RESUMO

Mitochondrial dysfunction has been implicated in a wide variety of degenerative diseases, including age-related macular degeneration. Damage to mitochondria and mitochondrial DNA accumulates with age in the postmitotic retinal pigment epithelium (RPE), which could lead to RPE cell death and trigger disease. One possible mechanism for cells to avoid cell death is mitophagy, the targeted clearance of damaged mitochondria by autophagy. Here, we induced mitochondrial damage in human RPE cells (ARPE-19 and hRPE), using antimycin A, an inhibitor of complex III of the electron transport chain, and investigated cellular viability, mitochondrial structure and function, and autophagy activity. We observed that antimycin A evoked dose-dependent cell death, a rapid loss in mitochondrial membrane potential, and a collapse of oxidative phosphorylation. Mitochondria appeared swollen and there was clear damage to their cristae structure. At the same time, cells were undergoing active autophagy and were sensitive to autophagy inhibition by bafilomycin A1 or chloroquine. These results indicate that mitochondrial dysfunction can cause significant RPE damage and that autophagy is an important survival mechanism for cells suffering from mitochondrial damage.


Assuntos
Antimicina A/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Mitocôndrias/patologia , Epitélio Pigmentado da Retina/patologia , Idoso , Linhagem Celular , Transporte de Elétrons/efeitos dos fármacos , Feminino , Glicólise/efeitos dos fármacos , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Fosforilação Oxidativa/efeitos dos fármacos , Fenótipo , Epitélio Pigmentado da Retina/ultraestrutura
17.
Photosynth Res ; 141(3): 303-314, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31004254

RESUMO

When plants suffer from abiotic stresses, cyclic electron flow (CEF) is induced for photo-protection. Putrescine (Put), a primary polyamine in chloroplasts, plays a critical role in stress tolerance. However, the relationship between CEF and Put in chloroplasts for photo-protection is unknown. In this study, we investigated the role of Put-induced CEF for salt tolerance in cucumber plants (Cucumis sativus L). Treatment with 90 mM NaCl and/or Put did not influence the maximum photochemical efficiency of PSII (Fv/Fm), but the photoactivity of PSI was severely inhibited by NaCl. Salt stress induced a high level of CEF; moreover, plants treated with both NaCl and Put exhibited much higher CEF activity and ATP accumulation than those exhibited by single-salt-treated plants to provide an adequate ATP/NADPH ratio for plant growth. Furthermore, Put decreased the trans-membrane proton gradient (ΔpH), which was accompanied by reduced pH-dependent non-photochemical quenching (NPQ) and an increased the effective quantum yield of PSII (Y(II)). The ratio of NADP+/NADPH increased significantly with Put in salt-stressed leaves compared with the ratio in leaves treated with NaCl, indicating that Put relieved over-reduction pressure at the PSI acceptor side caused by salt stress. Collectively, our results suggest that exogenous Put creates an excellent condition for CEF promotion: a large amount of pmf is predominantly stored as Δψ, resulting in moderate lumen pH and low NPQ, while maintaining high rates of ATP synthesis (high pmf).


Assuntos
Cucumis sativus/fisiologia , Cucumis sativus/efeitos da radiação , Luz , Putrescina/farmacologia , Estresse Salino/efeitos da radiação , Trifosfato de Adenosina/metabolismo , Clorofila/metabolismo , Cucumis sativus/efeitos dos fármacos , Cucumis sativus/crescimento & desenvolvimento , Transporte de Elétrons/efeitos dos fármacos , Transporte de Elétrons/efeitos da radiação , Fluorescência , Modelos Biológicos , NADP/metabolismo , Fenótipo , Fotossíntese/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/fisiologia , Proteínas de Plantas/metabolismo , Força Próton-Motriz , Estresse Salino/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/fisiologia , Cloreto de Sódio/farmacologia
18.
Chemosphere ; 224: 892-899, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30986895

RESUMO

Mechanisms of pharmaceuticals action on biochemical and physiological processes in plants that determine plant growth and development are still mostly unknown. This study deals with the effects of non-steroidal anti-inflammatory drug diclofenac (DCF) on photosynthesis as an essential anabolic process. Changes in primary and secondary photosynthetic processes were assessed in chloroplasts isolated from Lemna minor exposed to 1, 10, 100, and 1000 µM DCF. Decreases in the potential and effective quantum yields of photosystem II (FV/FM by 21%, ΦII by 44% compared to control), changes in non-photochemical fluorescence quenching (NPQ), and a substantial drop in Hill reaction activity (by 73%), especially under 1000 µM DCF, were found. Limitation of electron transport through photosystem II was confirmed by increased fluorescence signals in steps J and I (by 50% and 23%, respectively, under 1000 µM DCF) in OJIP fluorescence transient. Photosystem I exhibited changes only in the redox state of P700 reaction centres (decrease in Pm by 10%, increase in reduced P700 by 5% under 1000 µM DCF). Similarly, RuBisCO activity was only lowered by 30% under 1000 µM DCF. In contrast, a significant increase in reactive oxygen and nitrogen species (by 116% and 157%, respectively) was observed under 10 µM DCF, and lipid peroxidation increased even at 1 µM DCF (by nearly seven times compared to the control). Results demonstrate the ability of environmentally relevant DCF concentrations to induce oxidative stress in isolated duckweed chloroplasts; however, photosynthetic processes were affected considerably only by the highest DCF treatments.


Assuntos
Araceae/efeitos dos fármacos , Araceae/ultraestrutura , Cloroplastos/metabolismo , Diclofenaco/toxicidade , Fotossíntese/efeitos dos fármacos , Araceae/crescimento & desenvolvimento , Cloroplastos/efeitos dos fármacos , Diclofenaco/farmacologia , Transporte de Elétrons/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Complexo de Proteína do Fotossistema I , Complexo de Proteína do Fotossistema II/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/metabolismo
19.
Mol Pharmacol ; 95(6): 638-651, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30979813

RESUMO

Evofosfamide (TH-302) is a hypoxia-activated DNA-crosslinking prodrug currently in clinical development for cancer therapy. Oxygen-sensitive activation of evofosfamide depends on one-electron reduction, yet the reductases that catalyze this process in tumors are unknown. We used RNA sequencing, whole-genome CRISPR knockout, and reductase-focused short hairpin RNA screens to interrogate modifiers of evofosfamide activation in cancer cell lines. Involvement of mitochondrial electron transport in the activation of evofosfamide and the related nitroaromatic compounds EF5 and FSL-61 was investigated using 143B ρ 0 (ρ zero) cells devoid of mitochondrial DNA and biochemical assays in UT-SCC-74B cells. The potency of evofosfamide in 30 genetically diverse cancer cell lines correlated with the expression of genes involved in mitochondrial electron transfer. A whole-genome CRISPR screen in KBM-7 cells identified the DNA damage-response factors SLX4IP, C10orf90 (FATS), and SLFN11, in addition to the key regulator of mitochondrial function, YME1L1, and several complex I constituents as modifiers of evofosfamide sensitivity. A reductase-focused shRNA screen in UT-SCC-74B cells similarly identified mitochondrial respiratory chain factors. Surprisingly, 143B ρ 0 cells showed enhanced evofosfamide activation and sensitivity but had global transcriptional changes, including increased expression of nonmitochondrial flavoreductases. In UT-SCC-74B cells, evofosfamide oxidized cytochromes a, b, and c and inhibited respiration at complexes I, II, and IV without quenching reactive oxygen species production. Our results suggest that the mitochondrial electron transport chain contributes to evofosfamide activation and that predicting evofosfamide sensitivity in patients by measuring the expression of canonical bioreductive enzymes such as cytochrome P450 oxidoreductase is likely to be futile.


Assuntos
Transporte de Elétrons/efeitos dos fármacos , Mitocôndrias/genética , Neoplasias/genética , Nitroimidazóis/farmacologia , Mostardas de Fosforamida/farmacologia , Análise de Sequência de RNA/métodos , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Células HCT116 , Humanos , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Pró-Fármacos , RNA Interferente Pequeno/farmacologia
20.
Epilepsy Res ; 152: 35-41, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30875635

RESUMO

Generalized seizures trigger excessive neuronal firing that imposes large demands on the brain glucose/lactate availability and utilization, which synchronization requires an integral mitochondrial oxidative capability. We investigated whether a single convulsive crisis affects brain glucose/lactate availability and mitochondrial energy production. Adult male Wistar rats received a single injection of pentylentetrazol (PTZ, 60 mg/kg, i.p.) or saline. The cerebrospinal fluid (CSF) levels of glucose and lactate, mitochondrial respirometry, [14C]-2-deoxy-D-glucose uptake, glycogen content and cell viability in hippocampus were measured. CSF levels of glucose and lactate (mean ± SD) in control animals were 68.08 ± 11.62 mg/dL and 1.17 ± 0.32 mmol/L, respectively. Tonic-clonic seizures increased glucose levels at 10 min (96.25 ± 13.19) peaking at 60 min (113.03 ± 16.34) returning to control levels at 24 h (50.12 ± 12.81), while lactate increased at 10 min (3.23 ± 1.57) but returned to control levels at 360 min after seizures (1.58 ± 0.21). The hippocampal [14C]-2-deoxy-D-glucose uptake, glycogen content, and cell viability decreased up to 60 min after the seizures onset. Also, an uncoupling between mitochondrial oxygen consumption and ATP synthesis via FoF1-ATP synthase was observed at 10 min, 60 min and 24 h after seizures. In summary, after a convulsive seizure glucose and lactate levels immediately rise within the brain, however, considering the acute impact of this metabolic crisis, mitochondria are not able to increase energy production thereby affecting cell viability.


Assuntos
Glucose/líquido cefalorraquidiano , Ácido Láctico/líquido cefalorraquidiano , Mitocôndrias/metabolismo , Convulsões/líquido cefalorraquidiano , Animais , Desoxiglucose/metabolismo , Modelos Animais de Doenças , Transporte de Elétrons/efeitos dos fármacos , Etanolaminas/toxicidade , Glicogênio/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Masculino , Mitocôndrias/efeitos dos fármacos , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA