Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.214
Filtrar
1.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(3): 296-302, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31496162

RESUMO

OBJECTIVE: To investigate the effects of high dose vitamin C (VC) on proliferation of breast cancer cells and to explore its mechanisms. METHODS: Human breast cancer cells Bcap37 and MDA-MB-453 were treated with VC at low dose (0.01 mmol/L), medium dose (0.10 mmol/L) and high dose (2.00 mmol/L). Cell proliferation was determined with CCK-8 assay, protein expression was evaluated by Western blot, and the secretion of lactic acid in tumor cells was detected by colorimetric method. Bcap37 cells were inoculated in nude mice, and tumor baring nude mice were intraperitoneally injected with high VC(4 g/kg, VC group, n=5)or normal saline (control group, n=5) for 24 d. Tumor weight and body weight were calculated. RESULTS: In vitro experiments demonstrated that high dose VC significantly inhibited cell proliferation in Bcap37 and MDA-MB-453 cells (all P<0.01); the expressions of Glut1 and mTOR signaling pathway-related proteins were decreased (all P<0.05); and the secretion of lactic acid was also markedly reduced (all P<0.05). In vivo experiment showed that the tumor weight was decreased in mice treated with high-dose VC as compared with control group (P<0.05), but no difference in body weights between two groups was observed. CONCLUSIONS: High dose VC may inhibit proliferation of breast cancer cells both in vitro and in vivo through reducing glycolysis and protein synthesis.


Assuntos
Ácido Ascórbico , Neoplasias da Mama , Glicólise , Biossíntese de Proteínas , Animais , Ácido Ascórbico/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Biossíntese de Proteínas/efeitos dos fármacos
2.
J Agric Food Chem ; 67(32): 8905-8918, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31380641

RESUMO

NAC TFs play crucial roles in response to abiotic stresses in plants. Here, ZmNAC071 was identified as a nuclear located transcriptional repressor. Overexpression of ZmNAC071 in Arabidopsis enhanced sensitivity of transgenic plants to ABA and osmotic stress. The expression levels of SODs, PODs, P5CSs, and AtMYB61 were inhibited by ZmNAC071, which results in reduced ROS scavenging and proline content, increased ROS level, and water loss. Besides, the expression levels of some ABA or abiotic stress-related genes, like ABIs, RD29A, DREBs, and LEAs were also significantly inhibited by ZmNAC071. Yeast one-hybrid assay demonstrated that ZmNAC071 specifically bound to the cis-acting elements containing CGT[G/A] core sequences in the promoter of stress-related genes, suggesting that ZmNAC071 may participate in the regulation of transcription of these genes through recognizing the core sequences CGT[G/A]. These results will facilitate further studies concerning the cis-elements and downstream genes targeted by ZmNAC071 in maize.


Assuntos
Arabidopsis/efeitos dos fármacos , Arabidopsis/fisiologia , Ácido Ascórbico/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/fisiologia , Fatores de Transcrição/genética , Zea mays/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação para Baixo/efeitos dos fármacos , Pressão Osmótica , Plantas Geneticamente Modificadas/genética , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Fatores de Transcrição/metabolismo
3.
Cell Physiol Biochem ; 53(2): 337-354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31373783

RESUMO

BACKGROUND/AIMS: The availability of truly maturated cardiomyocytic subtypes is a major prerequisite for cardiovascular cell replacement therapies. Pluripotent stem cells provide a suitable source for the development of new strategies to overcome enormous hurdles such as yield, purity and safety of in vitro generated cells. METHODS: To address these issues, we have refined existing forward programming protocols by combining forced exogenous overexpression of the early cardiovascular transcription factor Nkx2.5 with a αMHC-promoter-based antibiotic selection step. Additionally, we applied small molecules such as ascorbic acid to enhance cardiomyogenic differentiation efficiency. Subsequently, we evaluated the cell fate of the resulting cardiomyocytes on the mRNA as well as protein levels. The latter was performed using high-resolution confocal microscopy. Furthermore, we examined the response of the cells` beating activities to pharmacological substance administration. RESULTS: Our results reveal an apparent influence of Nkx2.5 on the cell fate of ESC-derived cardiomyocytes. Resulting single cells exhibit characteristics of early ventricular cardiomyocytes, such as sarcomeric marker expression, spontaneous beating frequency, and distinct L-type calcium channel occurrence. CONCLUSION: Therefore, we demonstrate cardiovascular subtype forward programming of ESCs using a combination of transcription factors along with small molecule administration. However, our findings also underline current assumptions, that a terminal maturation of PSC derived cardiomyocytes in vitro is still an unsolved problem which urgently needs to be addressed in the field.


Assuntos
Reprogramação Celular , Células-Tronco Embrionárias/metabolismo , Proteína Homeobox Nkx-2.5/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Ácido Ascórbico/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Embrionárias/citologia , Proteína Homeobox Nkx-2.5/antagonistas & inibidores , Proteína Homeobox Nkx-2.5/genética , Camundongos , Microscopia Confocal , Miócitos Cardíacos/citologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Verapamil/farmacologia
4.
Chem Biol Interact ; 311: 108776, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369745

RESUMO

Omeprazole (OM), a prototype proton pump inhibitor, oxidizes thiol groups and induces DNA damage. The aim of this study was to evaluate the oxidative effects of omeprazole and its interactions with ascorbic acid (AA, 50 µM) and retinol palmitate (RP) in proficient and deficient Saccharomyces cerevisiae strains, as well as levels of cytogenetic damage in Sarcoma 180 (S180) cells. Omeprazole was tested at concentrations of 10, 20 and 40 µg/mL, whereas H2O2 (10 mM), cyclophosphamide (20 mg/mL), and saline (0.9% NaCl solution) were employed as stressor, positive control, and negative control, respectively. Results revealed that omeprazole concentration-dependently induces oxidative effects in S. cerevisiae strains. However, omeprazole co-treated with ascorbic acid (50 µM) and retinol palmitate (100 IU) significantly modulated the oxidative damage inflected on the S. cerevisiae strains. Furthermore, omeprazole did not produce micronucleus formation and chromosomal bridges in S180 cells, but induced shoots. Significant increase in karyolysis and karyorrhexis were also observed with the omeprazole treated groups, which was modulated by co-treatment with ascorbic acid and retinol palmitate. Taken all together, it is suggested that ascorbic acid and retinol palmitate can substantially modulate the oxidative damage caused by omeprazole on the S. cerevisiae strains, however, much precaution is recommended with omeprazole and antioxidant co-treatment.


Assuntos
Ácido Ascórbico/farmacologia , Aberrações Cromossômicas/efeitos dos fármacos , Omeprazol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Vitamina A/análogos & derivados , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclofosfamida/toxicidade , Peróxido de Hidrogênio/toxicidade , Camundongos , Testes para Micronúcleos , Vitamina A/farmacologia
5.
Life Sci ; 232: 116657, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306660

RESUMO

AIMS: Constant development of chemotherapeutic strategies has considerably improved the efficiency of tumor treatment. However, adverse effects of chemotherapeutics enforce premature treatment cessation, which leads to the tumor recurrence and accelerated death of oncologic patients. Recently, sodium ascorbate (ASC) has been suggested as a promising drug for the adjunctive chemotherapy of glioblastoma multiforme (GBM) and prostate cancer (PC). To estimate whether ASC can interfere with tumor recurrence between the first and second-line chemotherapy, we analyzed the effect of high ASC doses on the expansion of cells in vitro and in vivo. MAIN METHODS: Brightfield microscopy-assisted approaches were used to estimate the effect of ASC (1-14 mM) on the morphology and invasiveness of human GBM, rat PC and normal mouse 3T3 cells, whereas cytostatic/pro-apoptotic activity of ASC was estimated with flow cytometry. These assays were complemented by the in vitro CellROX-assisted analyses of intracellular oxidative stress and in vivo estimation of GBM tumor invasion. KEY FINDINGS: ASC considerably decreased the proliferation and motility of GBM and PC cells. This effect was accompanied by intracellular ROS over-production and necrotic death of tumor cells, apparently resulting from their "autoschizis". In vivo studies demonstrated the retardation of GBM tumor growth and invasion in the rats undergone intravenous ASC administration, in the absence of detectable systemic adverse effects of ASC. SIGNIFICANCE: Our data support previous notions on anti-tumor activity of high ASC doses. However, autoschizis-related cell responses to ASC indicate that its application in human adjunctive tumor therapy should be considered with caution.


Assuntos
Ácido Ascórbico/administração & dosagem , Neoplasias Encefálicas/patologia , Proliferação de Células/efeitos dos fármacos , Glioblastoma/patologia , Animais , Ácido Ascórbico/farmacologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Glioblastoma/metabolismo , Humanos , Masculino , Camundongos , Invasividade Neoplásica , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo
6.
Environ Sci Pollut Res Int ; 26(22): 22338-22350, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154641

RESUMO

A pot experiment was performed to assess the useful effects of seed soaking or seedling foliar spray using 0.25 mM spermine (Spm), 0.50 mM spermidine (Spd), or 1 mM putrescine (Put) on heavy metal tolerance in wheat plants irrigated with water contaminated by cadmium (2 mM Cd2+ in CdCl2) or lead (2 mM Pb2+ in PbCl2). Cd2+ or Pb2+ presence in the growth medium resulted in significant reductions in growth and yield characteristics and activities of leaf peroxidase (POD), glutathione reductase (GR), ascorbic acid oxidase (AAO), and polyphenol oxidase (PPO) of wheat plants. In contrast, significant increases were observed for Cd2+ content in roots, leaves and grains, superoxide dismutase (SOD) and catalase (CAT) activities, radical scavenging activity (DPPH), reducing power capacity, and fragmentation in DNA in comparison to controls (without Cd2+ or Pb2+ addition). However, treating the Cd2+- or Pb2+-stressed wheat plants with Spm, Spd, or Put, either by seed soaking or foliar spray, significantly improved growth and yield characteristics and activities of POD, GR, AAO, PPO, SOD, and CAT, DPPH, and reducing power capacity in wheat plants. In contrast, Cd2+ levels in roots, leaves, and yielded grains, and fragmentation in DNA were significantly reduced compared with the stressed (with Cd2+ or Pb2+) controls. Generally, seed soaking treatments were more effective than foliar spray treatments. More specifically, seed priming in Put was the best treatment under heavy metal stress. Results of this study recommend using polyamines, especially Put, as seed soaking to relieve the adverse effects of heavy metals in wheat plants.


Assuntos
Antioxidantes/farmacologia , Inativação Metabólica/efeitos dos fármacos , Oxirredutases/metabolismo , Plântula/efeitos dos fármacos , Espermidina/farmacologia , Espermina/farmacologia , Superóxido Dismutase/metabolismo , Antioxidantes/química , Ácido Ascórbico/farmacologia , Cádmio/química , DNA , Genômica , Glutationa Redutase/metabolismo , Oxirredução , Peroxidases/metabolismo , Folhas de Planta/metabolismo , Poliaminas , Sementes/metabolismo , Espermidina/química , Triticum/crescimento & desenvolvimento
7.
J Food Sci ; 84(6): 1340-1345, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31112293

RESUMO

Barley sprouts and wheat sprouts have received much interest as functional foods in many countries. In this study, the effects of heat processing and extraction temperature on the bioactive components and antioxidative properties were examined in barley and wheat sprout teas. Both barley and wheat sprout teas were processed with two different methods (steaming or pan-roasting). Crude protein was increased, and moisture content was the lowest, in the roasted barley and wheat sprout teas. Total phenolics content and flavonoid contents were significantly higher in the roasted teas than in the steamed teas. Vitamin C content was the highest after an extraction temperature of 55 °C (24.05 mg/mL) in the roasted wheat sprout tea. Both roasted barley and wheat sprout teas exhibited the most antioxidative effects in vitro, demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging and nitrite-scavenging activities. Therefore, the roasting method can be considered an appropriate technique for the production of barley and wheat sprout teas. PRACTICAL APPLICATION: Barley and wheat sprouts have received much attention in recent years as functional food materials in many countries and can be consumed as a form of tea. Heat processing methods such as steaming and roasting were applied and compared to increase the bioactive components and antioxidative activity in barley and wheat sprout teas. We found that roasting showed higher bioactive components and antioxidative activity than steaming in both barley and wheat sprout teas. In addition, wheat sprouts tea showed better bioactive components and antioxidative activity compared with the barley sprout tea.


Assuntos
Antioxidantes/farmacologia , Bebidas/análise , Hordeum/química , Temperatura Alta , Extratos Vegetais/farmacologia , Plântula/química , Triticum/química , Antioxidantes/análise , Ácido Ascórbico/análise , Ácido Ascórbico/farmacologia , Compostos de Bifenilo/metabolismo , Culinária , Flavonoides/análise , Flavonoides/farmacologia , Humanos , Fenóis/análise , Fenóis/farmacologia , Picratos/metabolismo , Extratos Vegetais/química , Chá
8.
Int J Mol Sci ; 20(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067675

RESUMO

BACKGROUND: We have characterized a new reconstructed full-thickness skin model, T-Skin™, compared to normal human skin (NHS) and evaluated its use in testing anti-aging compounds. METHODS: The structure and layer-specific markers were compared with NHS using histological and immunohistological staining. In anti-aging experiments, T-SkinTM was exposed to retinol (10 µM) or vitamin C (200 µM) for 5 days, followed by immunohistological staining evaluation. RESULTS: T-Skin™ exhibits a well stratified, differentiated and self-renewing epidermis with a dermal compartment of functional fibroblasts. Epidermal (cytokeratin 10, transglutaminase 1), dermo-epidermal junction (DEJ) (laminin 5, collagen-IV, collagen VII) and dermally-located (fibrillin 1, procollagen I) biomarkers were similar to those in NHS. Treatment of T-Skin™ with retinol decreased the expression of differentiation markers, cytokeratin 10 and transglutaminase 1 and increased the proliferation marker, Ki67, in epidermis basal-layer cells. Vitamin C increased the expression of DEJ components, collagen IV and VII and dermal procollagen 1. CONCLUSIONS: T-Skin™ exhibits structural and biomarker location characteristics similar to NHS. Responses of T-Skin™ to retinol and vitamin C treatment were consistent with those of their known anti-aging effects. T-Skin™ is a promising model to investigate responses of epidermal, DEJ and dermal regions to new skin anti-ageing compounds.


Assuntos
Ácido Ascórbico/farmacologia , Envelhecimento da Pele , Pele/efeitos dos fármacos , Vitamina A/farmacologia , Vitaminas/farmacologia , Moléculas de Adesão Celular/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Fibrilina-1/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Queratina-10/metabolismo , Queratinócitos/efeitos dos fármacos , Pele/citologia
9.
Environ Sci Pollut Res Int ; 26(19): 19261-19271, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31065988

RESUMO

Cadmium (Cd) contamination in agricultural soils is a prevalent environmental issue and poses potential threats to food security. Foliar ascorbic acid might prove a potent tool to alleviate toxicity of Cd toxicity in maize. An experiment was conducted with objectives to study exogenous ascorbic acid-modulated improvements in physiochemical attributes of maize under Cd toxicity. The experiment was conducted under completely randomized design. Treatments were comprised of varying concentrations of foliar ascorbic acid viz. 0.0, 0.1, 0.3, and 0.5 mM of AsA. Toxicity of Cd decreased the maize growth, increased lipid peroxidation, disturbed protein metabolism, and reduced the antioxidant defense capabilities compared with the control. However, foliar AsA significantly improved maize growth and development, photosynthetic capabilities, and protein concentrations in Cd-stressed maize plants. Meanwhile, the malondialdehyde contents and hydrogen peroxide accumulation levels in Cd-stressed maize plants decreased remarkably with increasing AsA concentrations. Furthermore, the combined treatments conspicuously boosted activities of superoxide dismutase, peroxidase, catalase, and glutathione reductase under the Cd stress alone. In addition, the application of AsA reduced the Cd uptake by 10.3-12.3% in grains. Conclusively, foliar ascorbic acid alleviated the negative effects of Cd stress in maize and improved photosynthetic processes, osmolytes, and antioxidant defense systems.


Assuntos
Antioxidantes/metabolismo , Ácido Ascórbico/farmacologia , Cádmio/toxicidade , Poluentes do Solo/toxicidade , Zea mays/efeitos dos fármacos , Ácido Ascórbico/metabolismo , Cádmio/metabolismo , Relação Dose-Resposta a Droga , Peroxidação de Lipídeos/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Distribuição Aleatória , Poluentes do Solo/metabolismo , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo
10.
Food Chem ; 290: 114-124, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31000027

RESUMO

This study was undertaken to estimate the concentrations of the formed polycyclic aromatic hydrocarbons (PAHs) in heat-treated (boiled, pan-fried and grilled) meats collected from Egypt. Dietary intakes and cancer risks of PAHs among Egyptian adults were calculated. Benzo[a]pyrene (B[a]P)-induced mutagenicity and oxidative stress in human colon (CaCo-2) cell line and mechanisms behind such effects were also investigated. Finally, protection trials using rosmarinic (RMA) and ascorbic acids (ASA) were carried out. The results indicated formation of PAHs at high levels in the heat-treated meats. Calculated incremental life time cancer risk among Egyptian adults were 7.05179E-07, 7.00604 E-06 and 1.86069 E-05 due to ingestion of boiled, pan-fried and grilled meats, respectively. B[a]P-exposed CaCo-2 cells had high abilities for mutagenicity (490.05 ±â€¯21.37 His + revertants) and production of reactive oxygen species. RMA and ASA protected CaCo-2 cells via reduction of B[a]P-induced mutagenicity and oxidative stress and upregulation of phase II detoxification enzymes and xenobiotic transporters.


Assuntos
Ácido Ascórbico/farmacologia , Benzo(a)pireno/análise , Benzo(a)pireno/toxicidade , Cinamatos/farmacologia , Depsídeos/farmacologia , Temperatura Alta , Carne/análise , Estresse Oxidativo/efeitos dos fármacos , Adulto , Células CACO-2 , Colo/patologia , Citoproteção/efeitos dos fármacos , Egito , Humanos , Mutagênicos/análise , Mutagênicos/toxicidade , Medição de Risco
11.
Environ Sci Pollut Res Int ; 26(15): 15443-15457, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30941714

RESUMO

Cadmium (Cd) is an environmental pollutant that can get entry into human body via ingestion of contaminated foods causing multiple organ damage. This study aimed at monitoring Cd residues in 20 foodstuffs of animal origin that are commonly consumed in Egypt. Health risk assessment was conducted via calculation of Cd dietary intakes and non-carcinogenic target hazard quotient. An in vitro approach was performed to investigate the constitutive effects of Cd on human hepatoma (HepG2) cells under food-relevant concentrations. Trials to reduce Cd-induced adverse effects on HepG2 cells were done using rosmarinic (RMA) and ascorbic acids (ASA). The achieved results indicated contamination of the tested foodstuffs with Cd at high levels with potential human health hazards. Cd at food-relevant concentrations caused significant cytotoxicity to HepG2 cells. This may be attributed to induction of oxidative stress and inflammation, as indicated by the overexpression of stress and inflammatory markers. At the same time, Cd downregulated xenobiotic transporters and upregulated the proliferation factors. Co-exposure of HepG2 cells to Cd and micronutrients such as RMA and ASA led to recovery of cells from the oxidative damage, and subsequently cell viability was strongly improved. RMA and ASA ameliorated the biological responses of HepG2 cells to Cd exposure.


Assuntos
Ácido Ascórbico/farmacologia , Cádmio/química , Sobrevivência Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Cádmio/análise , Cinamatos/química , Cinamatos/farmacologia , Depsídeos/química , Depsídeos/farmacologia , Egito , Células Hep G2 , Humanos , Medição de Risco
12.
Artif Cells Nanomed Biotechnol ; 47(1): 1075-1084, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30942622

RESUMO

In this study, an attempt has been made to evaluate the effect of products of ß-galactosidase (ßGS) catalyzed reaction i.e. glucose and galactose and their structurally related compound vitamin C (VC) on the catalytic activity of native and PANI-CS-NC and PANI-CS-Ag-NC adsorbed ßGS. Results indicated a decline in catalytic activity of soluble enzyme in the presence of all investigated compounds. The order of inhibition was found to be VC < glucose < galactose. However, the immobilized preparations were found more resistant to inactivation caused by the added compounds. About 48% activity was retained by PANI-CS-Ag-NC-ßGS in the presence of galactose (5%, w/v), while the native enzyme exhibited only 18% of its original activity. A significant decrease in absorbance and fluorescence intensity was evaluated in soluble enzyme incubated in the presence of all investigated compounds. Three-dimensional fluorescence graphs, CD and FT-IR spectroscopic studies illustrated noteworthy conformational changes in the secondary structure and microenvironment of the soluble enzyme in the presence of VC and tested sugars. These results suggest that both PANI-CS-NC and PANI-CS-Ag-NC bound ßGS are more resistant to the exposure caused by the higher concentration of added glucose, galactose, and VC and, therefore, can be effectively utilized for the production of a hassle-free lactose nano-biosensor.


Assuntos
Compostos de Anilina/química , Quitosana/química , Inibidores Enzimáticos/farmacologia , Nanocompostos/química , Prata/química , beta-Galactosidase/antagonistas & inibidores , beta-Galactosidase/química , Ácido Ascórbico/farmacologia , Catálise , Enzimas Imobilizadas/antagonistas & inibidores , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Galactose/farmacologia , Glucose/farmacologia , Ligação Proteica , beta-Galactosidase/metabolismo
13.
J Stroke Cerebrovasc Dis ; 28(7): 1993-2002, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31029568

RESUMO

BACKGROUND: Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-ß accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood. METHODS: APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry. RESULTS: In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-ß plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-ß pathology and neuronal loss, alleviated neuroinflammation and oxidative stress. CONCLUSIONS: The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ácido Ascórbico/administração & dosagem , Encéfalo/efeitos dos fármacos , Transtornos Cerebrovasculares/tratamento farmacológico , Cistina/administração & dosagem , Glutamina/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Ácido Ascórbico/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/fisiopatologia , Doença Crônica , Cognição/efeitos dos fármacos , Cistina/farmacologia , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Glutamina/farmacologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , Mutação , Estresse Oxidativo/efeitos dos fármacos , Placa Amiloide
14.
Environ Sci Pollut Res Int ; 26(16): 16727-16741, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989610

RESUMO

Cadmium and mercury are non-biodegradable toxic metals that may cause many detrimental effects to the thyroid gland and blood. Vitamin C has been found to be a significant chain-breaking antioxidant and enzyme co-factor against metal toxicity and thus make them less available for animals. The current study was performed to find the effect of individual metals (cadmium and mercury), their co-administration, and the ameliorative effects of vitamin C on some of the parameters that indicate oxidative stress and thyroid dysfunction. Cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to eight treatment groups of the rabbits (1. control; 2. Vit C; 3. CdCl2; 4. HgCl2; 5. Vit C + CdCl2; 6. Vit C + HgCl2; 7. CdCl2 + HgCl2, and 8. Vit C + CdCl2 + HgCl2). After the biometric measurements of all experimental rabbits, biochemical parameters viz. triidothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and triglycerides were measured using commercially available kits. The results exhibited significant decline (p < 0.05) in mean hemoglobin, corpuscular hemoglobin, packed cell volume, T3 (0.4 ± 0.0 ng/ml), and T4 (26.3 ± 1.6 ng/ml) concentration. While, TSH (0.23 ± 0.01 nmol/l) and triglyceride (4.42 ± 0.18 nmol/l) were significantly (p < 0.05) increased but chemo-treatment with Vit C reduces the effects of Cd, Hg, and their co-administration but not regained the values similar to those of controls. This indicates that Vit C had a shielding effect on the possible metal toxicity. The Cd and Hg also found to accumulate in vital organs when measured by atomic absorption spectrophotometer. The metal concentration trend was observed as follows: kidney > liver > heart > lungs. It was concluded that Cd and Hg are toxic and tended to bioaccumulate in different organs and their toxic action can be subdued by vitamin C in biological systems.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Cádmio/toxicidade , Mercúrio/toxicidade , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue , Tireotropina/sangue , Animais , Peso Corporal/efeitos dos fármacos , Cádmio/metabolismo , Intoxicação por Metais Pesados , Hemoglobinas/análise , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Mercúrio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Glândula Tireoide/metabolismo
15.
Nat Rev Cancer ; 19(5): 271-282, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30967651

RESUMO

Over the past century, the notion that vitamin C can be used to treat cancer has generated much controversy. However, new knowledge regarding the pharmacokinetic properties of vitamin C and recent high-profile preclinical studies have revived interest in the utilization of high-dose vitamin C for cancer treatment. Studies have shown that pharmacological vitamin C targets many of the mechanisms that cancer cells utilize for their survival and growth. In this Opinion article, we discuss how vitamin C can target three vulnerabilities many cancer cells share: redox imbalance, epigenetic reprogramming and oxygen-sensing regulation. Although the mechanisms and predictive biomarkers that we discuss need to be validated in well-controlled clinical trials, these new discoveries regarding the anticancer properties of vitamin C are promising to help identify patient populations that may benefit the most from high-dose vitamin C therapy, developing effective combination strategies and improving the overall design of future vitamin C clinical trials for various types of cancer.


Assuntos
Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Epigênese Genética/efeitos dos fármacos , Humanos , Oxirredução/efeitos dos fármacos
16.
Plant Physiol Biochem ; 139: 419-427, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30986643

RESUMO

Oxidative stress generates reactive oxygen species which causes cell damage of living organisms and are normally detoxified by antioxidants. Indirect reports signify the damages caused by reactive oxygen species and neutralized by antioxidant, but the direct evidence to confirm this hypothesis is still unclear. To validate our hypothesis, an attempt was made in a diazotrophic bacterium (Azotobacter chroococcum Avi2) as a biological system, and hydrogen peroxide (H2O2) and ascorbic acid were used as oxidative stress and antioxidant supplement, respectively. Additionally, rice plant-growth attributes by Avi2 was also assessed under H2O2 and ascorbic acid. Results indicated that higher concentration of H2O2 (2.5 mM-4.5 mM) showed the complete mortality of Avi2, whereas one ppm ascorbic acid neutralized the effect of H2O2. Turbidity, colony forming unit, DNA quantity, nifH gene abundance, indole acetic acid and ammonia productions were significantly (p < 0.5) increased by 11.93%, 17.29%, 19.80%, 74.77%, 71.89%, and 42.53%, respectively in Avi2-treated with 1.5 mM H2O2 plus ascorbic acid compared to 1.5 mM H2O2 alone. Superoxide dismutase was significantly (p < 0.5) increased by 60.85%, whereas catalase and ascorbate peroxidase activities were significantly (p < 0.05) decreased by 64.28% and 68.88% in Avi2-treated with 1.5 mM H2O2 plus ascorbic acid compared to 1.5 mM H2O2 alone. Germination percentage of three rice cultivars (FR13a, Naveen and Sahbhagi dhan) were significantly (p < 0.5) increased by 20%, 13.33%, and 4%, respectively in Avi2-treated with 0.6 mM H2O2 plus ascorbic acid compared with uninoculated control. Overall, this study indicated that ascorbic acid formulation neutralizes the H2O2-oxidative stress and enhances the survivability and plant growth-promoting efficacy of A. chroococcum Avi2 and therefore, it may be used as an effective formulation of bio-inoculants in rice under oxidative stress.


Assuntos
Ácido Ascórbico/farmacologia , Azotobacter/fisiologia , Fixação de Nitrogênio/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Oryza/microbiologia , Antioxidantes , Peróxido de Hidrogênio/farmacologia , Fixação de Nitrogênio/fisiologia , Oryza/metabolismo , Estresse Oxidativo/efeitos dos fármacos
17.
Biomed Res Int ; 2019: 4518163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31008105

RESUMO

Inactivation of rabies virus is essential for rabies vaccine preparation where the inactivating compound that is currently recommended for rabies vaccine preparation is ß-propiolactone (ß-PL). This compound is considered better than phenol and formalin but it is expensive and potentially carcinogenic. Data revealed that Ascorbic acid (AA) with cupric ions could yield complete and irreversible inactivation of rabies virus without adversely affecting its antigenicity. Additionally, the results of testing the vaccine potency with the selected inactivating compounds were comparable (P<0.05), and ED50 was higher than the recommended World Health Organization (WHO) limits. The use of HemaGel (plasma substitute) for testing vaccine stabilization was compared with the currently used vaccine stabilizers (human albumin and lactose). HemaGel yielded better stability than the other tested stabilizers. Monitoring of cellular and humoral immune responses indicated that both the total IgG level against rabies vaccine and the IFN and IL5 levels obtained with the HemaGel-stabilized vaccines were higher than those obtained with human albumin- and lactose-stabilized vaccine candidates.


Assuntos
Imunogenicidade da Vacina/efeitos dos fármacos , Propiolactona/farmacologia , Vacinas Antirrábicas/farmacologia , Raiva/prevenção & controle , Albuminas/farmacologia , Animais , Anticorpos Antivirais/efeitos dos fármacos , Anticorpos Antivirais/imunologia , Ácido Ascórbico/farmacologia , Cercopithecus aethiops , Humanos , Imunoglobulina G/imunologia , Interferons/imunologia , Interleucina-5 , Lactose/química , Propiolactona/química , Raiva/imunologia , Raiva/virologia , Vacinas Antirrábicas/química , Vacinas Antirrábicas/genética , Vacinas Antirrábicas/imunologia , Vírus da Raiva/imunologia , Vírus da Raiva/patogenicidade , Potência de Vacina , Células Vero/virologia
18.
Pancreas ; 48(4): 555-567, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30946238

RESUMO

OBJECTIVES: Pancreatic carcinoma is one of the most aggressive cancers overcoming chemoresistance. Thus, novel compounds to complement the current antitumor agents are in need. Ocoxin oral solution (OOS) has proven antioxidant, anti-inflammatory, and antistromagenic properties. The aim of this study was to analyze the effect of OOS in an experimental pancreatic cancer model and its implication in stroma-related chemoresistance to paclitaxel and gemcitabine. METHODS: Murine pancreatic carcinoma 266-6 cells were treated with OOS to analyze cell cycle and to perform a mRNA comparative microarray study. Then the viability was assessed in combination with paclitaxel and/or gemcitabine. Chemoresistance induced by the medium taken from fibroblast cultures was also investigated on 6 human pancreatic carcinoma cell lines. Furthermore, an experimental model of pancreatic cancer was carried out to study the effect of OOS in vivo. RESULTS: Ocoxin oral solution enhances the cytotoxic effect of paclitaxel and gemcitabine, while it ameliorates the chemoresistance induced by fibroblast-derived soluble factors in human pancreatic cancer cells. The OOS also promotes the regulation of the expression of genes that are altered in pancreatic carcinoma and slows down 266-6 cell pancreatic tumor development in vivo. CONCLUSIONS: Ocoxin oral solution could be a potential complement to the chemotherapeutic drugs for pancreatic adenocarcinoma.


Assuntos
Adenocarcinoma/tratamento farmacológico , Ácido Ascórbico/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Vitamina B 12/farmacologia , Vitamina B 6/farmacologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Ácido Ascórbico/administração & dosagem , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Paclitaxel/administração & dosagem , Paclitaxel/farmacologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Extratos Vegetais/administração & dosagem , Soluções , Vitamina B 12/administração & dosagem , Vitamina B 6/administração & dosagem
19.
Pharmacol Rep ; 71(2): 351-356, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30831441

RESUMO

BACKGROUND: Drug-induced ototoxicity is still a main clinical problem in otolaryngology. It is widely known that aminoglycoside antibiotics combined with loop diuretics significantly contribute to permanent ototoxicity. The aim of this study was to find out whether ascorbic acid (vitamin C) is able to reverse or alleviate ototoxicity evoked by systemic (ip) administration of combination of amikacin and furosemide in experimental male albino Swiss mice. METHODS: Ototoxic combination of amikacin and furosemide was isobolographically evaluated based on the hearing threshold decreasing doses by 20% and 50% (TDD20 and TDD50), respectively. Linear regression analysis was used to determine the TDD20 and TDD50 values for amikacin, furosemide, vitamin C administered alone and in combination (at the fixed-ratio of 1:1). RESULTS: Vitamin C (in a dose of 500 mg/kg, ip) alleviated the impairment in hearing threshold evoked by combined ip administration of amikacin and furosemide (at the fixed-ratio of 1:1) in mice by reducing TDD50 values from 49.82 to 21.56 (p < 0.01). In contrast, vitamin C (500 mg/kg, ip) had no significant effect on TDD20 values for the combination of amikacin and furosemide at the fixed-ratio of 1:1. CONCLUSIONS: Vitamin C administered together with ototoxic drug combination of amikacin and furosemide reduced ototoxicity evoked by this two-drug combination in the experimental mice.


Assuntos
Amicacina/toxicidade , Ácido Ascórbico/farmacologia , Furosemida/toxicidade , Perda Auditiva/prevenção & controle , Amicacina/administração & dosagem , Animais , Antibacterianos/administração & dosagem , Antibacterianos/toxicidade , Ácido Ascórbico/administração & dosagem , Diuréticos/administração & dosagem , Diuréticos/toxicidade , Furosemida/administração & dosagem , Perda Auditiva/induzido quimicamente , Modelos Lineares , Masculino , Camundongos
20.
Nutrients ; 11(3)2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30818817

RESUMO

This study evaluated the effects of vitamin C on osteogenic differentiation and osteoclast formation, and the effects of vitamin C concentration on bone microstructure in ovariectomized (OVX) Wistar rats. Micro-computed tomography analysis revealed the recovery of bone mineral density and bone separation in OVX rats treated with vitamin C. Histomorphometrical analysis revealed improvements in the number of osteoblasts, osteoclasts, and osteocytes; the osteoblast and osteoclast surface per bone surface; and bone volume in vitamin C-treated OVX rats. The vitamin C-treated group additionally displayed an increase in the expression of osteoblast differentiation genes, including bone morphogenetic protein-2, small mothers against decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin, and type I collagen. Vitamin C reduced the expression of osteoclast differentiation genes, such as receptor activator of nuclear factor kappa-B, receptor activator of nuclear factor kappa-B ligand, tartrate-resistant acid phosphatase, and cathepsin K. This study is the first to show that vitamin C can inhibit osteoporosis by promoting osteoblast formation and blocking osteoclastogenesis through the activation of wingless-type MMTV integration site family/ß-catenin/activating transcription factor 4 signaling, which is achieved through the serine/threonine kinase and mitogen-activated protein kinase signaling pathways. Therefore, our results suggest that vitamin C improves bone regeneration.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Ácido Ascórbico/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Fator 4 Ativador da Transcrição/genética , Ração Animal , Animais , Densidade Óssea , Dieta , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoporose/prevenção & controle , Ovariectomia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteínas Wnt/genética , beta Catenina/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA