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1.
Angew Chem Int Ed Engl ; 60(38): 20943-20951, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34137148

RESUMO

Amplifying free radical production by chemical dynamic catalysis to cause oxidative damage to cancer cells has received extensive interest for cancer-specific therapy. The major challenge is inevitable negative modulation on the tumor microenvironment (TME) by these species, hindering durable effectiveness. Here we show for the first time an oxygen vacancy-rich Bi-based regulator that allows environment-adaptive free radical catalysis. Specifically, the regulator catalyzes production of highly toxic O2 .- and . OH in cancer cells via logic enzymatic reactions yet scavenges accumulation of free radicals and immunosuppressive mediators in TME-associated noncancerous cells. Atomic-level mechanistic studies reveal that such dual-modal regulating behavior is dominated by oxygen vacancies that well fit for free radical catalytic kinetics, along with distinguished cellular fates of this regulator. With this smart regulator, a "two birds with one shot" cancer dynamic therapy can be expected.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Oxigênio/farmacologia , Antineoplásicos/química , Catálise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Radicais Livres/química , Radicais Livres/farmacologia , Humanos , Neoplasias/patologia , Oxigênio/química , Tamanho da Partícula , Espectrofotometria Ultravioleta
2.
Molecules ; 26(3)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33503925

RESUMO

Due to the constantly growing interest in ingredients of natural origin, this study attempts to evaluate the possibility of using extracts from three Ayurvedic plants in preparations for the care and treatment of skin diseases. Therefore, studies of antioxidant properties were carried out using DPPH and ABTS radicals, obtaining 76% and 88% of these radical scavenging, respectively. A significant decrease in the intracellular level of free radicals and an increase in the activity of the antioxidant enzyme-superoxide dismutase by almost 60% were also observed. In addition, the extracts were assessed for anti-inflammatory and anti-aging properties, obtaining over 70% inhibition of lipoxygenase activity and almost 40% of collagenase. Additionally, the cytoprotective properties of the obtained extracts on skin cells, keratinocytes and fibroblasts, were demonstrated. To assess the content of biologically active compounds, HPLC-electrospray ionization (ESI)-MS/MS multiple reaction monitoring (MRM) analyses were performed. The obtained results show that all three analyzed plants are a valuable source of biologically active substances with desired properties in the context of skin cell protection. Particularly noteworthy is the extract of Epilobium angustifolium L., for which the most promising results were obtained.


Assuntos
Cosméticos/química , Cosméticos/farmacologia , Fármacos Dermatológicos/química , Fármacos Dermatológicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Benzotiazóis/farmacologia , Compostos de Bifenilo/farmacologia , Células Cultivadas , Cromatografia Líquida de Alta Pressão/métodos , Fibroblastos/efeitos dos fármacos , Radicais Livres/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Picratos/farmacologia , Ácidos Sulfônicos/farmacologia , Espectrometria de Massas em Tandem/métodos
3.
Free Radic Res ; 54(8-9): 687-693, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32972269

RESUMO

Found in various natural food products, many in vitro evidence indicated that resveratrol (RES) has been linked to neuroprotective and cardioprotective effects and prevent cancer development. However, human clinical trials have been conducted with varying results, making the usage of RES controversial. In this paper, we demonstrated that the drug RES could be conjugated with the high levels of endogenous GS• in cancer cells. 5,5-Dimethyl-1-Pyrroline-N-Oxide (DMPO) was employed to capture the GS•. The molecular mechanism of the reaction between RES and GS• was further studied by UV-Vis spectrometry, mass spectrometry and Density Functional Theory (DFT) calculations. Besides, the formation of the adduct GS-RES in cancer cell was obtained when RES was added during incubation. Further study indicated that over 77.6% of the RES was consumed in cancer cells. This study suggested that endogenous GS• may be one of the important factors to cause the depletion of anti-tumour drugs during chemotherapy, which should be paid special attention in clinical therapeutics and drug development.


Assuntos
Radicais Livres/uso terapêutico , Glutationa/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Resveratrol/uso terapêutico , Radicais Livres/farmacologia , Humanos , Resveratrol/farmacologia
4.
Angew Chem Int Ed Engl ; 59(47): 21032-21040, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-32667130

RESUMO

Free radicals with reactive chemical properties can fight tumors without causing drug resistance. Reactive oxygen species (ROS) has been widely used for cancer treatment, but regrettably, the common O2 and H2 O2 deficiency in tumors sets a severe barrier for sufficient ROS production, leading to unsatisfactory anticancer outcomes. Here, we construct a chlorine radical (. Cl) nano-generator with SiO2 -coated upconversion nanoparticles (UCNPs) on the inside and Ag0 /AgCl hetero-dots on the outside. Upon near-infrared (NIR) light irradiation, the short-wavelength emission UCNP catalyzes . Cl generation from Ag0 /AgCl with no dependence on O2 /H2 O2 . . Cl with strong oxidizing capacity and nucleophilicity can attack biomolecules in cancer cells more effectively than ROS. This . Cl stress treatment will no doubt broaden the family of oxidative stress-induced antitumor strategies by using non-oxygen free radicals, which is significant in the development of new anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Cloro/farmacologia , Radicais Livres/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cloro/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Radicais Livres/química , Raios Infravermelhos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Prata/química , Prata/farmacologia , Propriedades de Superfície
5.
Photochem Photobiol Sci ; 19(8): 1001-1009, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32589182

RESUMO

The interactions of dietary carotenoids, and particularly the xanthophylls in the macula, with singlet oxygen and three different oxy-radicals, (hydroxyl radical, nitrogen dioxide and the superoxide radical anion) are compared using pulsed laser and γ-techniques. The results give possible molecular mechanisms for the switch from anti-oxidant (protection) by carotenoids to pro-oxidant (damage) by carotenoids. The participation of oxygen in radical mechanisms in the presence of different carotenoids is compared for the different radicals. It is shown that the mechanistic role of oxygen differs very significantly for anti-/pro-oxidation by hydroxyl radicals when compared to nitrogen dioxide. Lutein was found to be an extremely good cell protector against hydroxyl radicals at all oxygen concentrations, including under physiological conditions.


Assuntos
Antioxidantes/farmacologia , Carotenoides/farmacologia , Oxigênio Singlete/farmacologia , Antioxidantes/química , Carotenoides/química , Radicais Livres/química , Radicais Livres/farmacologia , Raios gama , Lasers , Linfócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oxigênio Singlete/química
6.
Rev. Asoc. Med. Bahía Blanca ; 30(1): 20-27, 20 de junio de 2020.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1099865

RESUMO

Se evaluó la actividad gastroprotectora de la infusión proveniente de las hojas de Aloysia gratissima (Verbenaceae), especie nativa de interés medicinal que se desarrolla en el sudoeste bonaerense, utilizando un modelo de inducción de úlceras gástricas con etanol en ratones. Se realizó un tamizaje fitoquímico para detectar la presencia de compuestos que podrían ser responsables de la actividad gastroprotectora de la planta. Se determinó el contenido de fenoles totales y la capacidad atrapadora de radicales libres mediante el método del Folin-Ciocalteu y del 2,2'-difenil-1-picrilhidrazilo (DPPH), respectivamente. Los ensayos demostraron que la infusión de la planta, administrada por vía oral en dosis de 100, 500 y 1000 mg/kg, ejerció una gastroprotección significativa frente a la inducción de úlceras. Se detectó una actividad atrapadora de radicales libres de 47,5%, similar a la sustancia de referencia (BHT). El estudio fitoquímico detectó la presencia de flavonoides y otros polifenoles, sustancias con reconocida capacidad antioxidante. Estos metabolitos ejercen efectos protectores en diferentes modelos experimentales de inducción de úlceras mediante mecanismos que pueden involucrar la neutralización de radicales libres, lo que podría explicar la actividad gastroprotectora de la planta. Estos hallazgos requieren estudios adicionales de A. gratissima como una posible terapia frente a la úlcera gástrica. (AU)


The gastroprotective activity of the infusion from the leaves of Aloysia gratissima (Verbenaceae), a native species of medicinal interest growing in South West Buenos Aires, was evaluated in an ethanol-induced gastric ulcer model in mice. Phytochemical screening was carried out in order to determine the presence of compounds that could be responsible for the pharmacological effects of the plant. Total phenolic content and the free radical scavenging activity of the plant were determined using the Folin-Ciocalteu and the 2,2'-diphenyl1-picrylhydrazyl (DPPH) method, respectively. Assays demonstrated that the infusion, orally administered at 100, 500, and 1000 mg/kg doses, exerted a significant gastroprotection effect against ulcer induction (P<0,05). A free radical scavenging activity of 47.5% -similar to the reference substance (BHT)- was detected. Phytochemical screening revealed the presence of antioxidant compounds such as flavonoids and other phenolic compounds. These compounds exert protective effects in different experimental models of ulcer induction that could involve free radical neutralization, which could explain the gastroprotective activity of the plant. These promising results support additional studies of A. gratissima as a potential therapy against gastric ulcer. (AU)


Assuntos
Animais , Camundongos , Úlcera Gástrica/tratamento farmacológico , Verbenaceae/efeitos dos fármacos , Experiências Laboratoriais , Radicais Livres/farmacologia
7.
J Appl Microbiol ; 129(5): 1248-1260, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32358824

RESUMO

AIMS: The study aimed to investigate the inactivation efficacy and mechanisms of plasma activated water (PAW) on selected bacteria in planktonic state. METHODS AND RESULTS: Plasma activated water was generated using an atmospheric cold plasma jet at 15, 22 and 30 kV for 5 min. Escherichia coli, Listeria innocua, Staphylococcus aureus, Aeromonas hydrophila, Pseudomonas fluorescens and Shewanella putrefaciens were selected as the representative bacterial species. Each bacterial suspension was inoculated into PAW immediately after generation, and the viable counts at different exposure times of 0·5, 1, 3, 5 and 24 h during 4°C storage were measured to determine the inactivation efficacy. Scanning electron microscopy images of the bacteria were conducted to examine the structural changes. Physicochemical properties of PAW, including pH, conductivity, oxidation reduction potential (ORP), and reactive species of H2 O2 , NO2 - and NO3 - were measured. The results demonstrated that inactivation efficacy was in positive correlation with voltage and exposure time. Gram-negative bacteria were more susceptible to PAW than Gram-positive bacteria. Morphology damage was observed for all the bacterial species. PAW was significantly acidified, conductivity and ORP were significantly increased, and reactive species were detectable after 48 h. CONCLUSIONS: This study offered a better understanding of the inactivation mechanisms of PAW, and the inactivation efficacy can be affected by voltage, exposure time and bacterial species. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the potential usage of PAW as an alternative disinfectant.


Assuntos
Bactérias/efeitos dos fármacos , Desinfetantes/farmacologia , Gases em Plasma/química , Água/farmacologia , Bactérias/classificação , Desinfetantes/química , Radicais Livres/análise , Radicais Livres/farmacologia , Concentração de Íons de Hidrogênio , Viabilidade Microbiana/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Especificidade da Espécie , Água/química , Microbiologia da Água
8.
Int J Mol Sci ; 21(7)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32244335

RESUMO

Poly(methyl methacrylate) (PMMA)-based bone cement, which is widely used to affix orthopedic metallic implants, is considered bio-tolerant but lacks osteoconductivity and is cytotoxic. Implant loosening and toxic complications are significant and recognized problems. Here we devised two strategies to improve PMMA-based bone cement: (1) adding 4-methacryloyloxylethyl trimellitate anhydride (4-META) to MMA monomer to render it hydrophilic; and (2) using tri-n-butyl borane (TBB) as a polymerization initiator instead of benzoyl peroxide (BPO) to reduce free radical production. Rat bone marrow-derived osteoblasts were cultured on PMMA-BPO, common bone cement ingredients, and 4-META/MMA-TBB, newly formulated ingredients. After 24 h of incubation, more cells survived on 4-META/MMA-TBB than on PMMA-BPO. The mineralized area was 20-times greater on 4-META/MMA-TBB than PMMA-BPO at the later culture stage and was accompanied by upregulated osteogenic gene expression. The strength of bone-to-cement integration in rat femurs was 4- and 7-times greater for 4-META/MMA-TBB than PMMA-BPO during early- and late-stage healing, respectively. MicroCT and histomorphometric analyses revealed contact osteogenesis exclusively around 4-META/MMA-TBB, with minimal soft tissue interposition. Hydrophilicity of 4-META/MMA-TBB was sustained for 24 h, particularly under wet conditions, whereas PMMA-BPO was hydrophobic immediately after mixing and was unaffected by time or condition. Electron spin resonance (ESR) spectroscopy revealed that the free radical production for 4-META/MMA-TBB was 1/10 to 1/20 that of PMMA-BPO within 24 h, and the substantial difference persisted for at least 10 days. The compromised ability of PMMA-BPO in recruiting cells was substantially alleviated by adding free radical-scavenging amino-acid N-acetyl cysteine (NAC) into the material, whereas adding NAC did not affect the ability of 4-META/MMA-TBB. These results suggest that 4-META/MMA-TBB shows significantly reduced cytotoxicity compared to PMMA-BPO and induces osteoconductivity due to uniquely created hydrophilic and radical-free interface. Further pre-clinical and clinical validations are warranted.


Assuntos
Cimentos Ósseos/farmacologia , Compostos de Boro/farmacologia , Radicais Livres/farmacologia , Metacrilatos/farmacologia , Metilmetacrilatos/farmacologia , Osteogênese/efeitos dos fármacos , Animais , Artroplastia de Quadril , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cimentos Ósseos/química , Células da Medula Óssea/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Boranos , Compostos de Boro/química , Calcificação Fisiológica/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Radicais Livres/química , Interações Hidrofóbicas e Hidrofílicas , Masculino , Teste de Materiais , Metacrilatos/química , Metilmetacrilato/química , Metilmetacrilatos/química , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteogênese/genética , Fenótipo , Polimerização , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacologia , Próteses e Implantes , Ratos , Ratos Sprague-Dawley
9.
Biophys Chem ; 260: 106367, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32200213

RESUMO

This study was aimed to investigate the inhibition effect of thiol-type antioxidants on protein oxidative aggregation caused by free radicals and the underlying mechanisms using six different thiol-type antioxidants (N-acetyl-L-cysteine, methionine, taurine, alpha-lipoic acid, glutathione and thioproline), Cu2+-H2O2 as a free radical generator (mainly a hydroxyl radical generator) and bovine serum albumin as the model protein. The inhibition effect of these antioxidants on protein oxidative aggregation and protective effect against oxidative damage in mouse brain tissues were investigated using SDS-PAGE, intrinsic fluorescence, simultaneous fluorescence, thioflavin T fluorescence, Congo red absorbance and inverted microscope. The results showed that all six antioxidants could inhibit protein oxidative aggregation by scavenging free radicals. In addition, alpha-lipoic acid could also bind to proteins via hydrophobic interactions and thioproline could bind to proteins via hydrogen bonds and van der Waals forces, thereby showing much stronger inhibition effect than others. Moreover, alpha-lipoic acid and thioproline could effectively prevent oxidative damage of mouse brain tissues. These results suggest that alpha-lipoic acid and thioproline can effectively inhibit free radical-induced protein aggregation and brain damage, which are worth testing for further anti-Alzheimer properties.


Assuntos
Antioxidantes/farmacologia , Substâncias Protetoras/farmacologia , Soroalbumina Bovina/antagonistas & inibidores , Compostos de Sulfidrila/farmacologia , Animais , Antioxidantes/química , Encéfalo/efeitos dos fármacos , Bovinos , Radicais Livres/antagonistas & inibidores , Radicais Livres/química , Radicais Livres/farmacologia , Camundongos , Estrutura Molecular , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Agregados Proteicos/efeitos dos fármacos , Soroalbumina Bovina/metabolismo , Compostos de Sulfidrila/química
10.
Sci Rep ; 10(1): 3396, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32099012

RESUMO

Malignant melanoma is considered to be a heterogeneous disease that arises from altered genes and transformed melanocytes. In this study, special softjet cold atmospheric plasma was used to treat three different human melanoma cells using air and N2 gases to check the anti-melanoma activity. The physical effects by plasma revealed an increase in the temperature with the gradual reduction in pH at 60 sec, 180 sec and 300 sec air and N2 plasma treatment. Cellular toxicity revealed a decreased in cell survival (~50% cell survival using air gas and <~60% cell survival using N2 gas at 60 sec plasma treatment in G-361 cells). Gene analysis by q-PCR revealed that 3 min and 5 min air and N2 plasma treatment activated apoptotic pathways by triggering apoptotic genes in all three melanoma cell lines. The apoptosis was confirmed by DAPI staining and its related pathways were further explored according to protein-protein docking, and their probable activation mechanism was revealed. The pathways highlighted that activation of apoptosis which leads to cellular cascades and hence stimulation ASK1 (docking method) revealed that softjet plasma can be an effective modality for human melanoma treatment.


Assuntos
Apoptose , Simulação por Computador , Melanoma/metabolismo , Gases em Plasma , Linhagem Celular Tumoral , Radicais Livres/química , Radicais Livres/farmacologia , Humanos , Gases em Plasma/química , Gases em Plasma/farmacologia
11.
J Neurosurg Sci ; 64(3): 258-262, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31957998

RESUMO

BACKGROUND: The aim of this registry study in patients with Parkinson's Disease (PD) in treatment, was to evaluate the effects of Pycnogenol® supplementation on some accessory symptoms and cognitive functions (COFU). METHODS: The registry included 43 PD patients who had been diagnosed at least one year before the start of the study. The PD condition was considered mild, with minimal progression. The management for these patients was a monotherapy using carbidopa/levodopa (standard management; SM). Supplementary Pycnogenol® was used at 150 mg/day for 4 weeks. The neurological management was not affected. RESULTS: Tolerability and safety were very good; the two registry groups were comparable with comparable symptoms at baseline. The most disabling symptoms were considered tremor, bradychinesia, alterations in COFU, rigidity and speech changes. All symptoms were rated as mild-to-moderate. After 4 weeks, these target symptoms were significantly attenuated with the supplement in comparison with the SM only (P<0.05). Particularly the COFU score was significantly higher (P<0.05) with the supplement. No interference between the main neurological management and the supplement was observed. Oxidative stress (plasma free radicals), high in both registry groups at inclusion, was significantly lower in the supplement group at 4 weeks (P<0.05). The main PD-associated items (cognitive aspects, motory and postural aspects) considered the most common and disturbing problems were evaluated and scored (0 to 4) with a visual scale line. At 4 weeks, the scores for all items were lower in the supplement group in comparison with the control, SM group. Peripheral edema was present in all patients at inclusion. The edema was minimal at inclusion (at the ankle-foot level with pretibial extension) and present in all subjects. It changed in two SM subjects and was still present at 4 weeks in 19 out 22 of the SM patients. In the supplemented patients, edema (present at inclusion in all subjects), was visible in 4 subjects out of 21 (19%) at 4 weeks. CONCLUSIONS: Pycnogenol® supplementation may help in selected patients with PD - under stable neurological treatment - to improve some signs and symptoms and some aspects associated with COFU. Studies are in progress on a larger population sample and with new evaluation methods.


Assuntos
Disfunção Cognitiva/prevenção & controle , Suplementos Nutricionais , Radicais Livres/farmacologia , Doença de Parkinson/tratamento farmacológico , Carbidopa/farmacologia , Cognição/efeitos dos fármacos , Combinação de Medicamentos , Feminino , Humanos , Levodopa/farmacologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Sistema de Registros
12.
Foodborne Pathog Dis ; 17(3): 228-233, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31647339

RESUMO

Salmonella spp. are among the most important pathogens in poultry farming, and Salmonella Heidelberg (SH) is one of the most frequent serotypes isolated in Brazil. SH has a zoonotic potential and stands out as a pathogen that is difficult to eliminate from the poultry chain due to its resistance to disinfectants. One alternative to traditional disinfectants is the electrochemically-activated water (ECA), a bactericidal compound produced from the electrolysis of salt and water. ECA generators produce a compound that consists of free chlorine, hypochlorous acid, and other free radicals. This alternative control method is safe for human health and reduces environmental contamination. The present study aimed at evaluating the efficacy of ECA against 30 SH isolates from poultry origin in scenarios that simulated the chiller environment (4°C, 5 and 50 parts per million [ppm], 5 and 40 min of exposure) and the cleaning and disinfection process (25°C, 200 ppm, 5 and 10 min of exposure). In the quantitative test, SH was susceptible to ECA. The mean bacterial counts decreased significantly compared to the control group, especially at 200 ppm. At this concentration, ECA inhibited the growth of almost 87% of the Salmonella strains, and the results showed a significant decrease in the mean bacterial counts for both exposure times (5 and 10 min). These findings demonstrate that ECA is effective against SH in vitro and it is a possible alternative to disinfection in the poultry industry for the control of this pathogen. However, in situ tests in the food industry are needed.


Assuntos
Desinfetantes/farmacologia , Desinfecção/métodos , Aves Domésticas/microbiologia , Salmonella/efeitos dos fármacos , Água/química , Animais , Brasil , Cloro/farmacologia , Contagem de Colônia Microbiana , Eletroquímica , Eletrólise , Contaminação de Alimentos , Microbiologia de Alimentos , Radicais Livres/farmacologia , Ácido Hipocloroso/farmacologia , Salmonella/isolamento & purificação , Sais/farmacologia
13.
Amino Acids ; 52(1): 35-53, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31781908

RESUMO

Hexavalent chromium [(Cr(VI)] is widely used in several industries, but human exposure results in multiple organ toxicity. Enhanced generation of free radicals and reactive species is thought to play a key role in Cr(VI)-induced toxicity. We have examined the effect of taurine, a simple sulphur-containing amino acid and an antioxidant, on potassium dichromate [K2Cr2O7, a Cr(VI) compound]-induced cytotoxicity and genotoxicity in human blood cells. Erythrocytes were treated with K2Cr2O7, either alone or after incubation with different concentrations of taurine. Treatment of erythrocytes with K2Cr2O7 alone led to marked increase in generation of reactive oxygen and nitrogen species, lipid and protein oxidation. This was accompanied by decrease in total sulfhydryl and glutathione content and lowered antioxidant power of the cells. This suggests that Cr(VI) induces oxidative stress in the cells. Incubation of erythrocytes with taurine prior to addition of K2Cr2O7, resulted in a concentration-dependent decrease in the generation of reactive oxygen and nitrogen species, mitigation of oxidative stress and amelioration of antioxidant power of these cells. It also restored the activities of several metabolic, antioxidant and membrane-bound enzymes. Cr(VI)-induced damage to erythrocyte membrane and lymphocyte DNA was also significantly attenuated by prior administration of taurine. These results suggest that taurine can function as a chemoprotectant against Cr(VI)-induced oxidative injury and can be potentially used to mitigate the toxic effects of this transition metal ion.


Assuntos
Antioxidantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Taurina/farmacologia , Antioxidantes/química , Cromo/toxicidade , Eritrócitos/efeitos dos fármacos , Radicais Livres/química , Radicais Livres/farmacologia , Glutationa/química , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Taurina/química
14.
Phytochemistry ; 170: 112218, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812108

RESUMO

The vast majority of previous studies dealing with antioxidant potency of (poly)phenols does not investigate the fate of phenoxyl radical obtained after single free radical scavenging. We investigated possible pathways of inactivation of ferulic acid phenoxyl radical (FAPR) using DFT method. Direct coupling with a set of 10 physiologically important free radicals, H-atom donation and dimerization were analysed by estimation of Gibbs free energy changes related to these processes. The former two processes are thermodynamically feasible to inactivate more dangerous free radicals such as hydroxyl, alkoxyl and carbon-centered radicals. Among dimerization reactions, the least energy demanding is formation of C-5-C-5 dimer of ferulic acid (FA), which has higher antiradical potency than FA itself. Obtained results reveal that FAPR, a priori considered as stable and unreactive, may contribute to the overall antioxidant activity of FA. This is a beneficial behavior, which makes FA a particularly valuable protector against oxidative stress. Hence, the contribution of phenoxyl radicals to the antioxidant activity of (poly)phenolic compounds should be taken into account, what has been scarcely considered until now.


Assuntos
Antioxidantes/farmacologia , Ácidos Cumáricos/farmacologia , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Antioxidantes/química , Ácidos Cumáricos/química , Teoria da Densidade Funcional , Radicais Livres/química , Radicais Livres/farmacologia , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Compostos Fitoquímicos/química
15.
ACS Nano ; 13(11): 13144-13160, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31609581

RESUMO

Tumor cell metabolism and tumor blood vessel proliferation are distinct from normal cells. The resulting tumor microenvironment presents a characteristic of hypoxia, which greatly limits the generation of oxygen free radicals and affects the therapeutic effect of photodynamic therapy. Here, we developed an oxygen-independent free radical generated nanosystem (CuFeSe2-AIPH@BSA) with dual-peak absorption in both near-infrared (NIR) regions and utilized it for imaging-guided synergistic treatment. The special absorption provides the nanosystem with high photothermal conversion efficiency and favorably matched photoactivity in both I and II NIR biological windows. Upon NIR light irradiation, the generated heat could prompt AIPH release and decompose to produce oxygen-independent free radicals for killing cancer cells effectively. The contrastive research results show that the enhanced therapeutic efficacy of NIR-II over NIR-I is principally due to its deeper tissue penetration and higher maximum permission exposure that benefits from a longer wavelength. Hyperthermia effect and the production of toxic free radicals upon NIR-II laser illumination are extremely effective in triggering apoptosis and death of cancer cells in the tumor hypoxia microenvironment. The high biocompatibility and excellent anticancer efficiency of CuFeSe2-AIPH@BSA allow it to be an ideal oxygen-independent nanosystem for imaging-guided and NIR-II-mediated synergistic therapy via systemic administration.


Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Neoplasias da Mama/tratamento farmacológico , Hipertermia Induzida , Hipóxia/terapia , Fotoquimioterapia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Radicais Livres/administração & dosagem , Radicais Livres/química , Radicais Livres/farmacologia , Raios Infravermelhos , Camundongos , Imagem Óptica
16.
Eur J Med Chem ; 178: 687-704, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31228811

RESUMO

Free radicals generated due to exposure of radiation, environmental pollutants and as by-products of metabolised drugs. These free radicals are antagonized by molecules which are antioxidant in nature. Antioxidants are the substances which inhibit oxidation. They are moreover acknowledged as "free radical scavengers" as they form minor reactive species via radicals. Based on origin, they are categorised into two types: exogenous and endogenous antioxidants. An Antioxidant reduces the occurrence of different disorders like: aging, cancer, diabetes, inflammation, liver disease, cardiovascular disease, cataract and nephrotoxicity and neurodegenerative disorders. Dietary antioxidants are thought to have potential capacities to avert oxidative anxiety induced diseases. This review figures the various researches on pharmacological activity of natural along with synthetic antioxidant molecules.


Assuntos
Antioxidantes/farmacologia , Antioxidantes/química , Radicais Livres/química , Radicais Livres/farmacologia , Humanos , Estresse Oxidativo/efeitos dos fármacos
17.
Mini Rev Med Chem ; 19(13): 1030-1039, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30836911

RESUMO

Nature offers tremendous potential in the medicine field. Natural antioxidant molecules inhibit or quench free radical reactions and delay or inhibit cellular damage. In the last few years, researchers have been focusing on the health benefits of natural products. Particularly some dietary nutrients, such as curcumin, crocin, resveratrol, quercetin, coenzyme Q10, vitamin C, as well as some polysaccharides have been evaluated for their numerous and unique therapeutic properties. This review focuses on examples of pharmaceutical applications of natural anti-oxidants, with special regards to their encapsulation in micro- and nano- delivery systems. In vitro and in vivo studies have been conducted to investigate the physicochemical and pharmacological properties of different delivery systems containing antioxidant molecules. For instance, ethosomes, organogels, monoolein aqueous dispersions and solid lipid nanoparticle have been considered. It was found that micro and nanoencapsulation strategy can improve the solubility of lipophilic molecules and the chemical stability of labile antioxidants, thus prolonging their efficacy. In vitro and in vivo studies have highlighted that antioxidant encapsulation prolongs release kinetics, bioavailability and antioxidant effects. Noticeably, some encapsulated antioxidants effectively inhibit cancer cell proliferation, cell migration and colony formation, thus suppressing cancer progression.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Sistemas de Liberação de Medicamentos , Antineoplásicos/química , Antioxidantes/química , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Radicais Livres/administração & dosagem , Radicais Livres/química , Radicais Livres/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
18.
Food Chem ; 286: 405-412, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30827625

RESUMO

The formation and properties of nanostructures during food processing have attracted much attention in recent years. Herein, the formation and physicochemical properties of fluorescence carbon dots (CDs) from baked lamb at different baking temperatures (200, 300, and 350 °C) were investigated. The morphology, surface functional groups and fluorescent quantum yield of the CDs were found to be highly dependent on the heating temperature. Biocompatibility of CDs investigation indicated that they were able to disperse onto both the cell membrane and the cytoplasm of HepG2 cells, and alter the cell cycle progression slightly. Moreover, the CDs from baked lamb of 350 °C showed the maximum scavenging capability to free radicals and could protect the cell from oxidative damage in vitro. This contribution represents the first report regarding the properties and formation process of CDs in baked lamb, providing valuable insights into baking temperature influence on physicochemical properties of the CDs.


Assuntos
Culinária , Pontos Quânticos/química , Carne Vermelha , Animais , Carbono/química , Membrana Celular/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Fluorescência , Radicais Livres/farmacologia , Células Hep G2 , Humanos , Pontos Quânticos/análise , Pontos Quânticos/toxicidade , Carneiro Doméstico , Espectrometria de Fluorescência , Temperatura
19.
Acta Clin Croat ; 58(4): 726-736, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32595258

RESUMO

This review article is focused on the impact of antioxidants and prooxidants on health with emphasis on the type of antioxidants that should be taken. Medical researchers suggest that diet may be the solution for the control of chronic diseases such as cardiovascular complications, hypertension, diabetes mellitus, and different cancers. In this survey, we found scientific evidence that the use of antioxidants should be limited only to the cases where oxidative stress has been identified. This is often the case of specific population groups such as postmenopausal women, the elderly, infants, workers exposed to environmental pollutants, and the obese. Before starting any supplementation, it is necessary to measure oxidative stress and to identify and eliminate the possible sources of free radicals and thus increased oxidative stress.


Assuntos
Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/fisiopatologia , Radicais Livres/farmacologia , Radicais Livres/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Free Radic Biol Med ; 130: 343-347, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30391676

RESUMO

Nitroxide free radicals can serve as redox-sensitive MRI contrast agents useful to image the redox status of tissue of interest. In this study, the effect of oxygen content in the inspired gas on the kinetics of metabolism of three nitroxides has been evaluated in the muscle and tumor in mice. SCC tumors (approximate size of 1.0 cm3) on the right hind leg of female C3H/Hen MTV- mice were prepared. Three nitroxides, 3-carboxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CxP), 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP), and 4-hydroxy-tetramethylpiperidine-N-oxyl (TEMPOL), having different lipophilicities were compared using MR redox imaging. T1-mapping of the tissues was obtained using a multi-slice multi-echo (MSME) sequence with several TRs. The three nitroxides showed differences in accumulation and metabolism/clearance in muscle and tumor. The cell impermeable nitroxide CxP displayed kinetic patterns of slow enhancement followed by a slow decline typical of clearance rather than metabolism. The cell permeable CmP on the other hand showed a relatively faster uptake and metabolism with a modestly higher rate of metabolism in the tumor than muscle. The TEMPOL on the other hand displayed a rapid uptake and reduction with a trend of significantly rapid decay rate in tumor tissue, while slightly higher maximum signal intensity and slower decay rate was observed in normal muscle. The reduction rate of TEMPOL in the tumor was significantly enhanced when the breathing gas had 100%-oxygen while it was not significantly different in the muscle. EPR oximetry studies monitoring the oxygen dependent linewidth of TEMPOL showed that the pO2 in the healthy tissue during carbogen breathing significantly increased normal tissue pO2 compared to air breathing whereas breathing 100%-oxygen made normal tissue slight hypoxic. Since TEMPOL is a radioprotector, our studies show that a combination of 100%-oxygen breathing and TEMPOL has a potential to enhance radioprotective effects to normal tissue.


Assuntos
Radicais Livres/farmacologia , Óxidos de Nitrogênio/farmacologia , Oxigênio/metabolismo , Protetores contra Radiação/farmacologia , Animais , Meios de Contraste/farmacologia , Óxidos N-Cíclicos/farmacologia , Humanos , Cinética , Imageamento por Ressonância Magnética , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Óxidos de Nitrogênio/química , Oxirredução/efeitos dos fármacos , Oximetria , Pirrolidinas/farmacologia , Protetores contra Radiação/química , Marcadores de Spin
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