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1.
ACS Appl Mater Interfaces ; 13(38): 45149-45160, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34520182

RESUMO

The removal of uremic toxins from patients with acute kidney injury is a key issue in improving the quality of life for people requiring peritoneal dialysis. The currently utilized method for the removal of uremic toxins from the human organism is hemodialysis, performed on semipermeable membranes where the uremic toxins, along with small molecules, are separated from proteins and blood cells. In this study, we describe a mixed-linker modulated synthesis of zirconium-based metal-organic frameworks for efficient removal of uremic toxins. We determined that the efficient adsorption of uremic toxins is achieved by optimizing the ratio between -amino functionalization of the UiO-66 structure with 75% of -NH2 groups within organic linker structure. The maximum adsorption of hippuric acid and 3-indoloacetic acid was achieved by UiO-66-NH2 (75%) and by UiO-66-NH2 (75%) 12.5% HCl prepared by modulated synthesis. Furthermore, UiO-66-NH2 (75%) almost completely adsorbs 3-indoloacetic acid bound to bovine serum albumin, which was used as a model protein to which uremic toxins bind in the human body. The high adsorption capacity was confirmed in recyclability test, which showed almost 80% removal of 3-indoloacetic acid after the third adsorption cycle. Furthermore, in vitro cytotoxicity tests as well as hemolytic activity assay have proven that the UiO-66-based materials can be considered as potentially safe for hemodialytic purposes in living organisms.

2.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361786

RESUMO

Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.


Assuntos
Antioxidantes/farmacologia , Betula/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Acetaldeído/antagonistas & inibidores , Acetaldeído/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Betula/classificação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Malondialdeído/antagonistas & inibidores , Camundongos , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Casca de Planta/classificação , Extratos Vegetais/química , Polônia , Superóxidos/antagonistas & inibidores , Triterpenos/química , Triterpenos/isolamento & purificação
3.
Psychopharmacology (Berl) ; 238(10): 2947-2961, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34268586

RESUMO

RATIONALE: Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. OBJECTIVES: The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress - CMUS) on the liability to mephedrone-induced reward in Wistar rats. METHODS: The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. RESULTS: Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats' prefrontal cortex and hippocampus. CONCLUSIONS: Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

4.
Mol Neurobiol ; 58(9): 4413-4424, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34021482

RESUMO

Mephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.

5.
Int J Mol Sci ; 22(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33579030

RESUMO

Neuroinflammation plays an essential role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Although coumarins have been shown to improve cognitive function in animal models and exert anti-inflammatory effects in cell cultures, the exact mechanism of their neuroprotective effects has not yet been fully elucidated. The present study aimed to investigate the neuroprotective effects of xanthotoxin (furanocoumarin) and umbelliferone (simple coumarin) in lipopolysaccharide-induced cognitive dysfunction in mice. For evaluation memory and learning processes, a passive avoidance test was used. Furthermore, acetylcholinesterase level and impact on the tumor necrosis factor α, interleukin 10 levels in the whole brain, and cyclooxygenase-II in hippocampus was established. Subchronic administration of both coumarins (15 mg/kg) enhanced the learning and memory function, but only the xanthotoxin improved cognitive processes impaired by lipopolysaccharide (0.8 mg/kg) administration. Behavioral results stay in line with acetylcholinesterase level in the brain. A statistically significant decrease in the level of tumor necrosis factor α and cyclooxygenase-II in lipopolysaccharide-treated rodents after coumarins' administration was observed. Together, our findings demonstrate that both coumarins improved cognitive functions, but only xanthotoxin significantly enhanced the learning and memory function and reduced the level of acetylcholinesterase in lipopolysaccharide-treated mice. This effect may suggest that only furanocoumarin-xanthotoxin attenuates neuroinflammation and enhances cholinergic neurotransmission, thus it can be a potential remedy with procognitive potential effective in treatment of neuroinflammatory disease.


Assuntos
Amnésia/tratamento farmacológico , Cognição/efeitos dos fármacos , Metoxaleno/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Umbeliferonas/uso terapêutico , Amnésia/induzido quimicamente , Animais , Lipopolissacarídeos , Locomoção/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos
6.
Front Neurosci ; 14: 730, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903765

RESUMO

Bergapten is a furanocoumarin naturally occurring in the Apiaceae family and it is a well-known photosensitizing agent used in photochemotherapy. In this study, we investigated the influence of bergapten on cognitive function and mechanism underlying these effects in scopolamine-induced memory impairment in male Swiss mice. The passive avoidance test was used to evaluate the efficiency of memory acquisition and consolidation. The results demonstrated that both single and repeated administration of bergapten improved not only the acquisition but also consolidation of memory. The behavioral tests showed that bergapten prevented memory impairment induced by administration of scopolamine. Observed effects may result from the inhibition of acetylcholinesterase activity in the hippocampus and prefrontal cortex. Also, bergapten caused significant anti-oxidative effects. These new findings provide pharmacological and biochemical support for the development of the coumarin's potential in cognitive deficits.

7.
Talanta ; 174: 633-637, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28738633

RESUMO

Carlina genus plants e.g. Carlina acanthifolia subsp. utzka have been still used in folk medicine of many European countries and its biological activity is mostly associated with root essential oils. In the present paper, Raman spectroscopy (RS) was applied for the first time for evaluation of essential oil distribution in root of C. acnthifolia subsp. utzka and identification of root structures containing the essential oil. Furthermore, RS technique was applied to assess chemical stability of oil during drying of plant material or distillation process. Gas chromatography-mass spectrometry was used for qualitative and quantitative analysis of the essential oil. The identity of compounds was confirmed using Raman, ATR-IR and NMR spectroscopy. Carlina oxide was found to be the main component of the oil (98.96% ± 0.15). The spectroscopic study showed the high stability of essential oil and Raman distribution analysis indicated that the oil reservoirs were localized mostly in the structures of outer layer of the root while the inner part showed nearly no signal assigned to the oil. Raman spectroscopy technique enabled rapid, non-destructive direct analysis of plant material with minimal sample preparation and allowed straightforward, unambiguous identification of the essential oil in the sample.


Assuntos
Asteraceae/química , Óleos Voláteis/química , Raízes de Plantas/química , Análise Espectral Raman , Óxidos/química
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