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1.
Metab Brain Dis ; 39(4): 589-609, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38351421

RESUMO

This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations' effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice.


Assuntos
Amnésia , Curcumina , Modelos Animais de Doenças , Nanocápsulas , Animais , Curcumina/farmacologia , Curcumina/administração & dosagem , Curcumina/uso terapêutico , Camundongos , Masculino , Amnésia/tratamento farmacológico , Amnésia/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Escopolamina
2.
Pharmaceutics ; 16(2)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38399323

RESUMO

Therapies for the treatment of pain and inflammation continue to pose a global challenge, emphasizing the significant impact of pain on patients' quality of life. Therefore, this study aimed to investigate the effects of 4-(Phenylselanyl)-2H-chromen-2-one (4-PSCO) on pain-associated proteins through computational molecular docking tests. A new pharmaceutical formulation based on polymeric nanocapsules was developed and characterized. The potential toxicity of 4-PSCO was assessed using Caenorhabditis elegans and Swiss mice, and its pharmacological actions through acute nociception and inflammation tests were also assessed. Our results demonstrated that 4-PSCO, in its free form, exhibited high affinity for the selected receptors, including p38 MAP kinase, peptidyl arginine deiminase type 4, phosphoinositide 3-kinase, Janus kinase 2, toll-like receptor 4, and nuclear factor-kappa ß. Both free and nanoencapsulated 4-PSCO showed no toxicity in nematodes and mice. Parameters related to oxidative stress and plasma markers showed no significant change. Both treatments demonstrated antinociceptive and anti-edematogenic effects in the glutamate and hot plate tests. The nanoencapsulated form exhibited a more prolonged effect, reducing mechanical hypersensitivity in an inflammatory pain model. These findings underscore the promising potential of 4-PSCO as an alternative for the development of more effective and safer drugs for the treatment of pain and inflammation.

3.
Chem Biol Interact ; 345: 109564, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34161785

RESUMO

Suppressive effect of bis (3-amino-2-pyridine) diselenide (BAPD) on psychiatric disorders - atopic dermatitis (AD) comorbidity in mice was investigated. To sensitize the animals, 2,4-dinitrochlorobenzene (DNCB) was applied to their dorsal skin on days 1-3. Mice were challenged with DNCB on their ears and dorsal skin on days 14, 17, 20, 23, 26, and 29. BAPD and Dexamethasone were administered to the animals, from days 14-29, and skin severity scores and behavioral tests were determined. Oxidative stress and inflammatory parameters were evaluated on the dorsal skin of mice. Na+, K+-ATPase activity and corticosterone levels were determined in hippocampus/cerebral cortex and plasma of mice, respectively. BAPD improved cutaneous damage, scratching behavior, inflammatory and oxidative stress markers. BAPD showed anxiolytic- and antidepressant-like effects and restored Na+, K+-ATPase activity and corticosterone levels. The present study was performed using female mice due the susceptibility for this disease. But, the evaluation of AD model in male mice would help to verify whether the male gender has the same predisposition to present this pathology. Our data demonstrated the suppressive effect of BAPD on psychiatric disorders - AD comorbidity by regulating inflammatory and oxidative status in mice.


Assuntos
Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/epidemiologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Siloxanas/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Comorbidade , Corticosterona/sangue , Corticosterona/metabolismo , Dermatite Atópica/complicações , Dermatite Atópica/metabolismo , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/complicações , Transtornos Mentais/complicações , Transtornos Mentais/metabolismo , Camundongos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Siloxanas/uso terapêutico
4.
Cell Biol Toxicol ; 26(6): 569-77, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20397041

RESUMO

The aim of this study was to investigate the protective effect of 3-alkynyl selenophene (3-ASP) on acute liver injury induced by carbon tetrachloride (CCl(4)) and 2-nitropropane (2-NP) in rats. On the first day of treatment, the animals received 3-ASP (25 mg/kg, p.o.). On the second day, the rats received CCl(4) (1 mg/kg, i.p.) or 2-NP (100 mg/kg, p.o.). Twenty-four hours after CCl(4) or 2-NP administration, the animals were euthanized, and their plasma and liver were removed for biochemical and histological analyses. The histological analysis revealed extensive injury in the liver of CCl(4)-exposed and 2-NP-exposed rats, which was attenuated by 3-ASP. 3-ASP significantly attenuated (1) the increase in plasmatic aspartate and alanine aminotransferase activities and lipid peroxidation levels induced by CCl(4) and 2-NP; (2) the inhibition of δ-aminolevulinic dehydratase activity caused by 2-NP; and (3) the decrease in ascorbic acid (AA) levels and catalase (CAT) activity caused by CCl(4). AA levels and CAT activity remained unaltered in the liver of rats exposed to 2-NP. The protective effect of 3-ASP on acute liver injury induced by CCl(4) and 2-NP in rats was demonstrated.


Assuntos
Alcinos/uso terapêutico , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Nitroparafinas/toxicidade , Compostos Organosselênicos/uso terapêutico , Propano/análogos & derivados , Substâncias Protetoras/uso terapêutico , Alcinos/farmacologia , Animais , Ácido Ascórbico/metabolismo , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Compostos Organosselênicos/farmacologia , Propano/toxicidade , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar
5.
RSC Adv ; 10(24): 13975-13983, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35498450

RESUMO

A simple and practical protocol for the synthesis of 3-selanyl-benzo[b]furans mediated by the SelectFluor® reagent was developed. This novel methodology provided a greener alternative to generate 3-substituted-benzo[b]furans via a metal-free procedure under mild conditions. The intramolecular cyclization reaction was carried out employing an electrophilic selenium species generated in situ through the reaction between SelectFluor® and organic diselenides. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy, and its reactivity was explored.

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