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1.
Antioxidants (Basel) ; 9(12)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33260982

RESUMO

A 12.4 kDa laminarin (LM) composed of ß(1→3)-glucan with ß(1→6)-branches was extracted from brown seaweed Lobophora variegata and modified via carboxylation using dielectric barrier discharge (LMC), conjugation with gallic acid (LMG), and sulfation (LMS). Analyses of the chemical composition of LMC, LMG, and LMS yielded 11.7% carboxyl groups, 1.5% gallic acid, and 1.4% sulfate content, respectively. Antioxidant activities of native and modified laminarins were assessed using six different in vitro methods. Sulfation stopped the antioxidant activities of LM. On the other hand, carboxylation improved cooper chelation (1.2 times). LMG was found to be a more efficient antioxidant agent than LM in terms of copper chelation (1.3 times), reducing power (1.3 times), and total antioxidant capacity (80 times). Gallic acid conjugation was further confirmed using Fourier transform infrared spectroscopy (FT-IR) and one- and two-dimensional NMR spectroscopy analyses. LMG also did not induce cell death or affect the cell cycle of Madin-Darby canine kidney (MDCK) cells. On the contrary, LMG protected MDCK cells from H2O2-induced oxidative damage. Taken together, these results show that LMG has the potent antioxidant capacity, and, therefore, potential applications in pharmacological and functional food products.

2.
J Inorg Biochem ; 210: 111133, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32619898

RESUMO

Nitric oxide (NO) and nitroxyl (HNO) have gained broad attention due to their roles in several physiological and pathophysiological processes. Remarkably, these sibling species can exhibit opposing effects including the promotion of angiogenic activity by NO compared to HNO, which blocks neovascularization. While many NO donors have been developed over the years, interest in HNO has led to the recent emergence of new donors. However, in both cases there is an expressive lack of iron-based compounds. Herein, we explored the novel chemical reactivity and stability of the trans-[Fe(cyclam)(NO)Cl]Cl2 (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex. Interestingly, the half-life (t1/2) for NO release was 1.8 min upon light irradiation, vs 5.4 h upon thermal activation at 37 °C. Importantly, spectroscopic evidence supported the generation of HNO rather than NO induced by glutathione. Moreover, we observed significant inhibition of NO donor- or hypoxia-induced HIF-1α (hypoxia-inducible factor 1α) accumulation in breast cancer cells, as well as reduced vascular tube formation by endothelial cells pretreated with the trans-[Fe(cyclam)(NO)Cl]Cl2 complex. Together, these studies provide the first example of an iron-nitrosyl complex with anti-angiogenic activity as well as the potential dual activity of this compound as a NO/HNO releasing agent, which warrants further pharmacological investigation.


Assuntos
Inibidores da Angiogênese/farmacologia , Complexos de Coordenação/farmacologia , Doadores de Óxido Nítrico/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/efeitos da radiação , Animais , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Glutationa/química , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ferro/química , Ferro/efeitos da radiação , Camundongos , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/síntese química , Doadores de Óxido Nítrico/efeitos da radiação , Óxidos de Nitrogênio/metabolismo , Ratos , Temperatura , Raios Ultravioleta , Vasodilatadores/síntese química , Vasodilatadores/farmacologia , Vasodilatadores/efeitos da radiação
3.
Int J Nanomedicine ; 15: 965-979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103950

RESUMO

BACKGROUND: Chagas disease, also known as American Trypanosomiasis, is caused by the protozoan Trypanosoma cruzi. It is occurring in Americas, including USA and Canada, and Europe and its current treatment involves the use of two drugs as follows: benznidazole (BNZ) and nifurtimox, which present high toxicity and low efficacy during the chronic phase of the disease, thus promoting the search for more effective therapeutic alternatives. Amongst them xylan, a bioactive polysaccharide, extracted from corn cob. METHODS: Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy (FITR), Raman spectroscopy, energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy, atomic force microscopy, plasma optical emission spectroscopy (ICP-OES), dynamic light scattering (DLS) have been used to characterize the silver-xylan nanoparticles (NX). Their cytotoxicity was evaluated with 3-bromo(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) test. MTT and flow cytometry were used to ascertain the anti-Trypanosoma cruzi activity. RESULTS: UV-Vis spectroscopy gave plasmon resonance ranging between 400 and 450 nm while FITC and Raman spectroscopy proved nano interface functionalized with xylan. ICP-OES data showed NX with xylan (81%) and silver (19%). EDS showed NX consisting of carbon (59.4%), oxygen (26.2%) and silver (4.8%) main elements. Spherical NX of 55 nm average size has been depicted with SEM and AFM, while DLS showed 102 ± 1.7 nm NX. The NX displayed negligible cytotoxicity (2000 µg/mL). NX (100 µg/mL) was more effective, regardless of experiment time, in affecting the ability of parasites to reduce MTT than BZN (100 µg/mL). In addition, NX (100 µg/mL) induced death of 95% of parasites by necrosis. CONCLUSION: This is the first time silver nanoparticles are presented as an anti-Trypanosoma cruzi agent and the data point to the potential application of NX to new preclinical studies in vitro and in vivo.


Assuntos
Nanopartículas Metálicas/química , Prata/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Xilanos/química , Animais , Doença de Chagas/tratamento farmacológico , Difusão Dinâmica da Luz , Nanopartículas Metálicas/uso terapêutico , Camundongos , Microscopia de Força Atômica , Células RAW 264.7 , Espectrometria por Raios X , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Tripanossomicidas/síntese química , Zea mays/química
4.
Front Pharmacol ; 9: 1511, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30670966

RESUMO

The treatment of chronic wounds is considered a public health problem. When the condition affects at-risk groups such as those with diabetics, it becomes a great clinical challenge. In this work, we evaluated the healing effects of a new zinc complex, [Zn(phen)(van)2], identified as ZPV, which was synthesized, characterized and associated with chitosan (CS) membranes and tested on cutaneous wounds of diabetic rats. Chitosan membranes were modified by Schiff base reaction with the complex under two experimental conditions (14 and 21 days), resulting in membranes with concentrations of complex equal to 0.736 µmol cm-2 (CS-ZPV1) and 1.22 µmol cm-2 (CS-ZPV2). Release assays in aqueous medium indicated that the membranes release the complex gradually when exposed to an aqueous medium. Diabetes was inducted in Wistar rats using 40 mg/kg (i.v.) streptozotocin. On the 7th day after diabetic induction, a circular excision on the skin (1.0 cm) was performed with a punch. The lesions were treated with the pure chitosan membrane and the membrane associated with the zinc-vanillin complex in two different doses. Skin samples were subjected to macroscopic and histopathological analyses, cytokine (TNF-α, IL-1ß, and IL-10) quantification and reverse transcriptase polymerase chain reaction (TGF-ß and VEGF) assays. The analyses showed a decrease in wound size, reepithelialization, angiogenic stimulus, collagen deposition, and reduced levels of TNF-α and IL-1ß as well as increased IL-10 and gene expression of TGF-ß and VEGF. The evaluated parameters suggest that CS-ZPV in the two concentrations tested may be effective in the treatment of chronic wounds.

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