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1.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445561

RESUMO

Among numerous contaminants, the ubiquitous occurrence of nonsteroidal anti-inflammatory drugs (NSAIDs) in the environment and their plausible harmful impact on nontarget organisms have made them one of the most important areas of concern in recent years. Crop plants can also potentially be exposed to NSAIDs, since the concentration of these pharmaceuticals is constantly rising in the surface water and soil. Our goal was to evaluate the stress response of two crop plants, maize and tomato, to treatment with selected NSAIDs, naproxen and diclofenac. The focus of the research was on the growth response, photosynthetic efficiency, selected oxidative stress factors (such as the H2O2 level and the rate of lipid peroxidation) as well as the total phenolic content, which represents the non-enzymatic protectants against oxidative stress. The results indicate that susceptibility to the NSAIDs that were tested is dependent on the plant species. A higher sensitivity of tomato manifested in growth inhibition, a decrease in the content of the photosynthetic pigments and a reduction in the maximum quantum efficiency of PSII and the activity of PSII, which was estimated using the Fv/Fm and Fv/F0 ratios. Based on the growth results, it was also possible to reveal that diclofenac had a more toxic effect on tomato. In contrast to tomato, in maize, neither the content of the photosynthetic pigments nor growth appeared to be affected by DFC and NPX. However, both drugs significantly decreased in maize Fv and Fm, which are particularly sensitive to stress. A higher H2O2 concentration accompanied, in most cases, increasing lipid peroxidation, indicating that oxidative stress occurred in response to the selected NSAIDs in the plant species that were studied. The higher phenolic content of the plants after NSAIDs treatment may, in turn, indicate the activation of defense mechanisms in response to the oxidative stress that is triggered by these drugs.


Assuntos
Diclofenaco/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lycopersicon esculentum/efeitos dos fármacos , Naproxeno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Zea mays/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Peróxido de Hidrogênio/farmacologia , Lycopersicon esculentum/crescimento & desenvolvimento , Lycopersicon esculentum/metabolismo , Oxidantes/farmacologia , Fenóis/farmacologia , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo
2.
Chem Biol Interact ; 347: 109582, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34302802

RESUMO

Different aspects of reproductive functions are regulated by mitochondrial-controlled events. This study investigated the effect of plumbagin (PL) on testicular mitochondria with a view to unravelling the mechanism of the antifertility potential of plumbagin in testis of healthy rats. Thirty-two male Wistar strain albino rats were randomly allocated into four groups of eight animals each. The control or healthy group received orally 0.1 % DMSO while animals in the remaining three groups received 2.5 mg PL/kg bdwt, 5.0 mg PL/kg bdwt and 10 mg PL/kg bdwt, respectively, for 14 days. In study two, twenty-four male Wistar rats were randomly divided into three (3) groups and were orally administered 0.1% DMSO (control), 30 and 100 mg/kg PL, respectively once daily for 72 h. Rat testis mitochondria were isolated using differential centrifugation. The mitochondrial Permeability Transition (mPT) pore, mitochondrial ATPase (mATPase) activity and mitochondrial lipid peroxidation were assessed spectrophotometrically. Expression of apoptotic proteins (p53, Bax, Bcl-2) and the release of cytochrome c were determined by immunochemical technique. Reproductive receptors (FSH, PR), the expression of aromatase, Testis Specific Kinase-1 {TESK-1} were quantified by RT-PCR. The various doses of plumbagin (2.5, 5.0 and 10 mg/kg bdwt) induced opening of the testicular mPT pore by 2, 5 and 8 folds, respectively, after 14 days of oral administration. These doses of plumbagin also caused enhancement of mATPase activity, elevated generation of mLPO as well as increases in the concentrations of caspases 9 and 3. Sperm analysis revealed that these doses of PL also caused significant decreases in sperm count and motility and increased sperm abnormalities compared to control. Interestingly, these effects were accompanied by dose-dependent expressions of the Bak, p53 and cytochrome c release. Conversely, the abundance of anti-apoptotic Bcl-2 protein decreased relative to control. The levels of transcripts of FSH and progesterone receptors as well as TESK-1 and aromatase decreased significantly relative to control. Furthermore, PL strongly inhibited p53-MDM2 compared to control. Altogether, these findings show that plumbagin damages testicular cells through the activation of mitochondrial pathway involving the p53 protein network.


Assuntos
Morte Celular/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Naftoquinonas/farmacologia , Testículo/efeitos dos fármacos , Adenosina Trifosfatases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 9/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/metabolismo , Proteína Supressora de Tumor p53/metabolismo
3.
Nat Commun ; 12(1): 4299, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262038

RESUMO

Radiofrequency ablation (RFA) is clinically adopted to destruct solid tumors, but is often incapable of completely ablating large tumors and those with multiple metastatic sites. Here we develop a CaCO3-assisted double emulsion method to encapsulate lipoxidase and hemin with poly(lactic-co-glycolic acid) (PLGA) to enhance RFA. We show the HLCaP nanoreactors (NRs) with pH-dependent catalytic capacity can continuously produce cytotoxic lipid radicals via the lipid peroxidation chain reaction using cancer cell debris as the fuel. Upon being fixed inside the residual tumors post RFA, HLCaP NRs exhibit a suppression effect on residual tumors in mice and rabbits by triggering ferroptosis. Moreover, treatment with HLCaP NRs post RFA can prime antitumor immunity to effectively suppress the growth of both residual and metastatic tumors, also in combination with immune checkpoint blockade. This work highlights that tumor-debris-fueled nanoreactors can benefit RFA by inhibiting tumor recurrence and preventing tumor metastasis.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Nanomedicina/métodos , Neoplasias/terapia , Ablação por Radiofrequência , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Animais , Carbonato de Cálcio/química , Carbonato de Cálcio/uso terapêutico , Catálise , Linhagem Celular Tumoral , Terapia Combinada , Ferroptose/efeitos dos fármacos , Hemina/química , Hemina/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Inibidores de Checkpoint Imunológico/uso terapêutico , Morte Celular Imunogênica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoxigenase/química , Lipoxigenase/uso terapêutico , Camundongos , Metástase Neoplásica , Neoplasia Residual , Neoplasias/imunologia , Neoplasias/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/uso terapêutico , Coelhos
4.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199597

RESUMO

The disruption of iron homeostasis is an important factor in the loss of mitochondrial function in neural cells, leading to neurodegeneration. Here, we assessed the protective action of gossypitrin (Gos), a naturally occurring flavonoid, on iron-induced neuronal cell damage using mouse hippocampal HT-22 cells and mitochondria isolated from rat brains. Gos was able to rescue HT22 cells from the damage induced by 100 µM Fe(II)-citrate (EC50 8.6 µM). This protection was linked to the prevention of both iron-induced mitochondrial membrane potential dissipation and ATP depletion. In isolated mitochondria, Gos (50 µM) elicited an almost complete protection against iron-induced mitochondrial swelling, the loss of mitochondrial transmembrane potential and ATP depletion. Gos also prevented Fe(II)-citrate-induced mitochondrial lipid peroxidation with an IC50 value (12.45 µM) that was about nine time lower than that for the tert-butylhydroperoxide-induced oxidation. Furthermore, the flavonoid was effective in inhibiting the degradation of both 15 and 1.5 mM 2-deoxyribose. It also decreased Fe(II) concentration with time, while increasing O2 consumption rate, and impairing the reduction of Fe(III) by ascorbate. Gos-Fe(II) complexes were detected by UV-VIS and IR spectroscopies, with an apparent Gos-iron stoichiometry of 2:1. Results suggest that Gos does not generally act as a classical antioxidant, but it directly affects iron, by maintaining it in its ferric form after stimulating Fe(II) oxidation. Metal ions would therefore be unable to participate in a Fenton-type reaction and the lipid peroxidation propagation phase. Hence, Gos could be used to treat neuronal diseases associated with iron-induced oxidative stress and mitochondrial damage.


Assuntos
Flavonoides/farmacologia , Ferro/efeitos adversos , Mitocôndrias/metabolismo , Neurônios/citologia , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ácido Cítrico/efeitos adversos , Compostos Ferrosos/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos
5.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198914

RESUMO

The five-membered heterocyclic group of pyrazoles/pyrazolines plays important role in drug discovery. Pyrazoles and pyrazolines present a wide range of biological activities. The synthesis of the pyrazolines and pyrazole derivatives was accomplished via the condensation of the appropriate substituted aldehydes and acetophenones, suitable chalcones and hydrazine hydrate in absolute ethanol in the presence of drops of glacial acetic acid. The compounds are obtained in good yields 68-99% and their structure was confirmed using IR, 1H-NMR, 13C-NMR and elemental analysis. The novel derivatives were studied in vitro for their antioxidant, anti-lipid peroxidation (AAPH) activities and inhibitory activity of lipoxygenase. Both classes strongly inhibit lipid peroxidation. Compound 2g was the most potent lipoxygenase inhibitor (IC50 = 80 µM). The inhibition of the carrageenin-induced paw edema (CPE) and nociception was also determined, with compounds 2d and 2e being the most potent. Compound 2e inhibited nociception higher than 2d. Pyrazoline 2d was found to be active in a preliminary test, for the investigation of anti-adjuvant-induced disease (AID) activity. Pyrazoline derivatives were found to be more potent than pyrazoles. Docking studies of the most potent LOX inhibitor 2g highlight hydrophobic interactions with VAL126, PHE143, VAL520 and LYS526 and a halogen bond between the chlorine atom and ARG182.


Assuntos
Anti-Inflamatórios/síntese química , Inibidores de Lipoxigenase/síntese química , Lipoxigenase/química , Pirazóis/síntese química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Concentração Inibidora 50 , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoxigenase/metabolismo , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Pirazóis/química , Pirazóis/farmacologia , Ratos
6.
Molecules ; 26(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208180

RESUMO

The pyrazoline ring is defined as a "privileged structure" in medicinal chemistry. A variety of pharmacological properties of pyrazolines is associated with the nature and position of various substituents, which is especially evident in diarylpyrazolines. Compounds with a chalcone fragment show a wide range of biological properties as well as high reactivity which is primarily due to the presence of an α, ß-unsaturated carbonyl system. At the same time, bicyclic monoterpenoids deserve special attention as a source of a key structural block or as one of the pharmacophore components of biologically active molecules. A series of new diarylpyrazoline derivatives based on isobornylchalcones with different substitutes (MeO, Hal, NO2, N(Me)2) was synthesized. Antioxidant properties of the obtained compounds were comparatively evaluated using in vitro model Fe2+/ascorbate-initiated lipid peroxidation in the substrate containing brain lipids of laboratory mice. It was demonstrated that the combination of the electron-donating group in the para-position of ring B and OH-group in the ring A in the structure of chalcone fragment provides significant antioxidant activity of synthesized diarylpyrazoline derivatives.


Assuntos
Antioxidantes/síntese química , Antioxidantes/farmacologia , Chalconas/química , Pirazóis/síntese química , Pirazóis/farmacologia , Animais , Antioxidantes/química , Química Farmacêutica , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
7.
Toxicol Appl Pharmacol ; 426: 115638, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34242569

RESUMO

Gonadal development begins in the intrauterine phase and females from most species are born with an established oocyte reserve. Exposure to drugs during gestation can compromise the offspring health, also affecting the gametes quality. Nicotine, the main component of cigarettes, is an oxidant agent capable of altering the fertility in men and women. As female gametes are susceptible to oxidative stress, this drug can damage the oolemma and affect oocyte maturation, induce errors during chromosomal segregation and DNA fragmentation. Oocyte mitochondria are particularly susceptible to injuries, contributing to the oocyte quality loss and embryonic development disruption. Thus, considering the high number of women who smoke during pregnancy, while significant events are occurring in the embryo for future fertility of offspring, we seek to verify the quality of the oocytes from adult rats exposed to nicotine during intrauterine phase and breastfeeding. Pregnant Wistar rats received nicotine by osmotic mini-pumps and the female progenies were evaluated in adulthood for oocyte quality (viability, lipid peroxidation, generation of reactive oxygen species and mitochondrial integrity) and reproductive capacity. Embryos (3dpc) and fetuses (20dpc) generated by these rats were also evaluated. The results showed that the dose of 2 mg/kg/day of nicotine through placenta and breast milk does not affect the number of oocytes and the fertility capacity of adult rats. However, it causes some morphological alterations in oocytes, mitochondrial changes, embryonic fragmentation and disruption of fetal development. The malformations in fetuses generated from these gametes can also indicate the occurrence of epigenetic modifications.


Assuntos
Nicotina/toxicidade , Oócitos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Reprodução/efeitos dos fármacos , Animais , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Lactação , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Troca Materno-Fetal , Mitocôndrias/efeitos dos fármacos , Oócitos/metabolismo , Gravidez , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
8.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202188

RESUMO

Various natural compounds have been successfully tested for preventing or counteracting the toxic effects of exposure to heavy metals. In this study, we analyzed the effects of cadmium chloride (CdCl2) on immortalized, non-tumorigenic thyroid cells Nthy-ori-3-1. We investigated the molecular mechanism underlying its toxic action as well as the potential protective effect of quercetin against CdCl2-induced damage. CdCl2 suppressed cell growth in a dose- and time-dependent manner (IC50 value ~10 µM) associated with a decrease in levels of phospho-ERK. In addition, CdCl2 elicited an increase in reactive oxygen species (ROS) production and lipid peroxidation. A significant increase in GRP78, an endoplasmic reticulum (ER) stress-related protein, was also observed. Supplementation of quercetin counteracted the growth-inhibiting action of CdCl2 by recovering ERK protein phosphorylation levels, attenuating ROS overproduction, decreasing MDA content and reducing the expression of GRP78 in cells exposed to CdCl2. Thus, in addition to revealing the molecular effects involved in cadmium-induced toxicity, the present study demonstrated, for the first time, a protective effect of quercetin against cadmium-induced damages to normal thyroid cells.


Assuntos
Cádmio/toxicidade , Disruptores Endócrinos/toxicidade , Substâncias Protetoras/farmacologia , Quercetina/farmacologia , Glândula Tireoide/citologia , Glândula Tireoide/efeitos dos fármacos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cloreto de Cádmio/toxicidade , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Glândula Tireoide/metabolismo
9.
AAPS PharmSciTech ; 22(5): 200, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34212283

RESUMO

Mucositis is one of the most adverse effects of 5-fluorouracil (5-FU) and had no standard drug for treatment. Melatonin is a neurohormone, and can ameliorate radiotherapy-induced small intestinal mucositis. Melatonin encapsulated in niosomes improved its poor bioavailability. Succinyl melatonin, a melatonin derivative, showed prolonged release compared with melatonin. This study investigated the efficacy of melatonin niosome gel (MNG) and succinyl melatonin niosome gel (SNG) in 5-FU-induced small intestinal mucositis treatment in mice. MNG and SNG with particle sizes of 293 and 270 nm were shown to have mucoadhesive potentials. The effect of a daily oral application of MNG, SNG, or fluocinolone acetonide gel (FAG, positive control) was compared to that of the normal group. The body weight, food consumption, histology, Fourier transform infrared (FTIR) spectroscopy, inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1ß), and malondialdehyde (MDA) in the small intestine were monitored. The results showed decreased %body weight and food consumption in all 5-FU-injected groups compared with the normal group. The MNG and SNG treatments maintained the food consumption and the normal integrity of the small intestines, as evidenced by villus length and crypt depth, similar to the observations in the normal groups. The FTIR spectra showed no change in lipids of the MNG and SNG groups compared with the normal group. Moreover, SNG could reduce IL-1ß content to a level that was not different from the level in the normal groups. Therefore, the oral application of MNG and SNG could protect against 5-FU-induced small intestinal mucositis in mice.


Assuntos
Lipossomos/química , Melatonina/administração & dosagem , Mucosite/tratamento farmacológico , Administração Oral , Animais , Fluoruracila/toxicidade , Interleucina-1beta/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestino Delgado/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Melatonina/química , Melatonina/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Mucosite/induzido quimicamente , Mucosite/patologia , Tamanho da Partícula , Fator de Necrose Tumoral alfa/metabolismo
10.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202230

RESUMO

Prediabetes (PrDM) is a prodromal stage of diabetes mellitus (DM) with an increasing prevalence worldwide. During DM progression, individuals gradually develop complications in various organs. However, lungs are suggested to be affected later than other organs, such as the eyes, heart or brain. In this work, we studied the effects of PrDM on male Wistar rats' lungs and whether the regular consumption of white tea (WTEA) for 2 months contributes to the improvement of the antioxidant profile of this tissue, namely through improved activity of the first line defense antioxidant enzymes, the total antioxidant capacity and the damages caused in proteins, lipids and histone H2A. Our data shows that PrDM induced a decrease in lung superoxide dismutase and glutathione peroxidase activities and histone H2A levels and an increase in protein nitration and lipid peroxidation. Remarkably, the regular WTEA intake improved lung antioxidant enzymes activity and total antioxidant capacity and re-established the values of protein nitration, lipid peroxidation and histone H2A. Overall, this is the first time that lung is reported as a major target for PrDM. Moreover, it is also the first report showing that WTEA possesses relevant chemical properties against PrDM-induced lung dysfunction.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estado Pré-Diabético/metabolismo , Chá/química , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Glutationa Peroxidase/metabolismo , Histonas/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Extratos Vegetais/química , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
11.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208348

RESUMO

Antioxidants play a critical role in the treatment of degenerative diseases and delaying the aging of dermal tissue. Caffeic acid (CA) is a representative example of the antioxidants found in plants. However, CA is unsuitable for long-term storage because of its poor stability under ambient conditions. Caffeoyl-Pro-His-NH2 (CA-Pro-His-NH2, CA-PH) exhibits the highest antioxidant activity, free radical scavenging and lipid peroxidation inhibition activity among the histidine-containing CA-conjugated dipeptides reported to date. The addition of short peptides to CA, such as Pro-His, is assumed to synergistically enhance its antioxidative activity. In this study, several caffeoyl-prolyl-histidyl-Xaa-NH2 derivatives were synthesized and their antioxidative activities evaluated. CA-Pro-His-Asn-NH2 showed enhanced antioxidative activity and higher structural stability than CA-PH, even after long-term storage. CA-Pro-His-Asn-NH2 was stable for 3 months, its stability being evaluated by observing the changes in its NMR spectra. Moreover, the solid-phase synthetic strategy used to prepare these CA-Pro-His-Xaa-NH2 derivatives was optimized for large-scale production. We envision that CA-Pro-His-Xaa-NH2 derivatives can be used as potent dermal therapeutic agents and useful cosmetic ingredients.


Assuntos
Ácidos Cafeicos/síntese química , Ácidos Cafeicos/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Ácidos Cafeicos/química , Morte Celular/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Peróxidos/metabolismo , Picratos/química , Espectroscopia de Prótons por Ressonância Magnética , Técnicas de Síntese em Fase Sólida , Espectrometria de Massas por Ionização por Electrospray
12.
Molecules ; 26(9)2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34065080

RESUMO

The crude ethanol extract of the whole plant of Alternanthera philoxeroides (Mart.) Griseb was investigated for its potential as antidementia, induced by estrogen deprivation, based on in vitro antioxidant activity, ß-amyloid aggregation inhibition and cholinesterase inhibitory activity, as well as in vivo Morris water maze task (MWMT), novel object recognition task (NORT), and Y-maze task. To better understand the effect of the extract, oxidative stress-induced brain membrane damage through lipid peroxidation in the whole brain was also investigated. Additionally, expressions of neuroinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and estrogen receptor-mediated facilitation genes such as PI3K and AKT mRNA in the hippocampus and frontal cortex were also evaluated. These effects were confirmed by the determination of its serum metabolites by NMR metabolomic analysis. Both the crude extract of A. philoxeroides and its flavone constituents were found to inhibit ß-amyloid (Aß) aggregation.


Assuntos
Demência/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Metabolômica , Extratos Vegetais/farmacologia , Amaranthaceae/química , Peptídeos beta-Amiloides/química , Animais , Cognição/efeitos dos fármacos , Demência/prevenção & controle , Etanol/química , Etanol/farmacologia , Feminino , Flavonas/química , Sequestradores de Radicais Livres/metabolismo , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Medicina Tradicional do Leste Asiático , Metaboloma , Camundongos , Camundongos Endogâmicos ICR , Ovariectomia , Análise de Componente Principal , Fator de Necrose Tumoral alfa/metabolismo
13.
Molecules ; 26(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066803

RESUMO

2'-hydroxy-chalcones are naturally occurring compounds with a wide array of bioactivity. In an effort to delineate the structural features that favor antioxidant and lipoxygenase (LOX) inhibitory activity, the design, synthesis, and bioactivity profile of a series of 2'-hydroxy-chalcones bearing diverse substituents on rings A and B, are presented. Among all the synthesized derivatives, chalcone 4b, bearing two hydroxyl substituents on ring B, was found to possess the best combined activity (82.4% DPPH radical scavenging ability, 82.3% inhibition of lipid peroxidation, and satisfactory LOX inhibition value (IC50 = 70 µM). Chalcone 3c, possessing a methoxymethylene substituent on ring A, and three methoxy groups on ring B, exhibited the most promising LOX inhibitory activity (IC50 = 45 µM). A combination of in silico techniques were utilized in an effort to explore the crucial binding characteristics of the most active compound 3c and its analogue 3b, to LOX. A common H-bond interaction pattern, orienting the hydroxyl and carbonyl groups of the aromatic ring A towards Asp768 and Asn128, respectively, was observed. Regarding the analogue 3c, the bulky (-OMOM) group does not seem to participate in a direct binding, but it induces an orientation capable to form H-bonds between the methoxy groups of the aromatic ring B with Trp130 and Gly247.


Assuntos
Antioxidantes/química , Antioxidantes/metabolismo , Chalconas/química , Chalconas/metabolismo , Desenho de Fármacos , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/metabolismo , Lipoxigenase/metabolismo , Soja/enzimologia , Antioxidantes/farmacologia , Chalconas/farmacologia , Ligação de Hidrogênio , Radical Hidroxila , Concentração Inibidora 50 , Peroxidação de Lipídeos/efeitos dos fármacos , Inibidores de Lipoxigenase/farmacologia , Simulação de Acoplamento Molecular/métodos , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade
14.
Int J Biol Macromol ; 184: 463-475, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34171252

RESUMO

Biofilm composition from fish myofibrillar protein (FMP) and chitosan solution (CS) incorporated with rosemary extract (RE) was developed and applied to monitor the freshness of fish fillets. The effects of different concentrations of RE as well as physical, mechanical, structural and functional properties of FMP/CS films were investigated. Films containing RE showed reduced water solubility and water vapor permeability and enhanced tensile strength and elongation at break. Results also showed good compatibility of the components and good dispersion of RE in the matrix. However, the content of RE (0.2%, v/v) added in the composite films produced aggregations and had negative effects on their film-forming properties. The antioxidant capacity of composite films was related to the level of RE and demonstrated by the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay. Chilled grass carp fillets wrapped with different films to evaluate the preservative effect. Results of thiobarbituric acid reactive substances, pH value, Free amino acid and total volatile basic nitrogen indicated that FMP/CS/RE composite film could protect the fish fillet well and inhibit the lipid oxidation. The developed FMP/CS/RE composite films possess the potential to be applied as edible films in the food packaging industry and food cold chain transportation.


Assuntos
Antioxidantes/farmacologia , Quitosana/química , Proteínas Musculares/química , Extratos Vegetais/farmacologia , Rosmarinus/química , Animais , Antioxidantes/química , Carpas , Filmes Comestíveis , Proteínas de Peixes/química , Embalagem de Alimentos , Armazenamento de Alimentos , Peroxidação de Lipídeos/efeitos dos fármacos , Extratos Vegetais/química , Solubilidade , Vapor , Resistência à Tração
15.
Expert Opin Drug Metab Toxicol ; 17(7): 857-865, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34102941

RESUMO

BACKGROUND: Acrylamide (AA) is a water-soluble toxic chemical that is considered one of the most important food contaminants. Furthermore, AA is considered a major public health risk. METHODS: This study was designed to evaluate the effects of AA on cytotoxicity, oxidative damage and genotoxicity in human lymphocytes and also to evaluate the protective effects of the chrysin (CH). Lymphocytes after isolation from the blood were treated with AA (50 µM), AA (50 µM) plus CH (10, 25, 50 µM) and CH (50 µM), and parameters such as cell viability, mitochondrial and lysosomal damage, as well as oxidative damage to DNA were examined. RESULTS: The results showed that CH was able to reduce cytotoxicity, reactive oxygen species (ROS) levels, lipid peroxidation (LPO) level, collapse in mitochondrial membrane potential (MMP) and oxidative damage of DNA caused by AA in human lymphocytes. Also, co-treatment of the AA-exposed human lymphocytes with CH increases the glutathione (GSH) levels. CONCLUSION: Results suggest that CH (10, 25, 50 µM) shows a protective role in AA-induced cytotoxicity, oxidative stress, mitochondrial damage and DNA oxidative damage.


Assuntos
Acrilamida/toxicidade , Flavonoides/farmacologia , Linfócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Adulto , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Linfócitos/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
16.
Toxicol Appl Pharmacol ; 426: 115635, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34174262

RESUMO

The beneficial role of prasugrel, a P2Y12 receptor blocker, in several neurointerventional procedures has been reviewed clinically. Beyond its antiplatelet capacity, the potential neuroprotective mechanisms of prasugrel are poorly addressed experimentally. Relevant to the imbalance between neuro-inflammation and neuroprotective pathways in cerebral ischemia/reperfusion (I/R), our study evaluated the anti-ischemic potential of prasugrel treatment through tackling novel targets. Male Wistar rats were allocated into 2 sets; set 1 (I/R 60 min/3 days) to assess the neurological deficits/biochemical impact of prasugrel and set 2 (I/R 60 min/5 days) for evaluating short memory/morphological/immunoreactive changes. Each set comprised 4 groups designated as sham, sham + prasugrel, I/R, and I/R + prasugrel. Post-administration of prasugrel for 3 and 5 days reduced neurological deficit scores and improved the spontaneous activity/short term spatial memory using the Y-maze paradigm. On the molecular level, prasugrel turned off SUMO2/3-inhibitory kappa (Iκ)Bα, Ubc9 and nuclear factor kappa (NF-κ)B. Besides, it inhibited malondialdehyde (MDA) and inactivated astrocytes by downregulating the glial fibrillary acidic protein (GFAP) hippocampal immune-expression. Conversely, it activated its target molecule cAMP, protein kinase (PK)A, and cAMP response element-binding protein (CREB) to enhance the brain-derived nuclear factor (BDNF) hippocampal content. Additionally, cAMP/PKA axis increased the hippocampal content of deacetylator silent information regulator 1 (SIRT1) and the micro RNA (miR)-22 gene expression. The crosstalk between these paths partakes in preserving hippocampal cellularity. Accordingly, prasugrel, regardless inhibiting platelets activity, modulated other cellular components; viz., SUMO2/3-IκBα/Ubc9/NF-κB, cAMP/PKA related trajectories, CREB/BDNF and SIRT1/miR-22 signaling, besides inhibiting GFAP and MDA to signify its anti-ischemic potential.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Isquemia Encefálica/sangue , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , MicroRNAs/sangue , Inibidor de NF-kappaB alfa/metabolismo , Fármacos Neuroprotetores/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Cloridrato de Prasugrel/farmacologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Ratos Wistar , Sirtuína 1/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Memória Espacial/efeitos dos fármacos , Enzimas de Conjugação de Ubiquitina/metabolismo
17.
Biomed Pharmacother ; 140: 111732, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34130201

RESUMO

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.


Assuntos
Acetaminofen , Monoterpenos Acíclicos/uso terapêutico , Analgésicos não Narcóticos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Monoterpenos Acíclicos/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Catalase/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Globulinas/análise , Glutationa/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Ratos Wistar , Albumina Sérica/análise , Superóxido Dismutase/sangue , gama-Glutamiltransferase/sangue
18.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067102

RESUMO

Significant antibacterial properties of non-thermal plasma (NTP) have converted this technology into a promising alternative to the widespread use of antibiotics in assisted reproduction. As substantial data available on the specific in vitro effects of NTP on male reproductive cells are currently missing, this study was designed to investigate selected quality parameters of human spermatozoa (n = 51) exposed to diffuse coplanar surface barrier discharge NTP for 0 s, 15 s, 30 s, 60 s and 90 s. Sperm motility characteristics, membrane integrity, mitochondrial activity, production of reactive oxygen species (ROS), DNA fragmentation and lipid peroxidation (LPO) were investigated immediately following exposure to NTP and 2 h post-NTP treatment. Exposure to NTP with a power input of 40 W for 15 s or 30 s was found to have no negative effects on the sperm structure or function. However, a prolonged NTP treatment impaired all the sperm quality markers in a time- and dose-dependent manner. The most likely mechanism of action of high NTP doses may be connected to ROS overproduction, leading to plasma membrane destabilization, LPO, mitochondrial failure and a subsequent loss of motility as well as DNA integrity. As such, our findings indicate that appropriate plasma exposure conditions need to be carefully selected in order to preserve the sperm vitality, should NTP be used in the practical management of bacteriospermia in the future.


Assuntos
Gases em Plasma/farmacologia , Espermatozoides/fisiologia , Adulto , Apoptose/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Superóxidos/metabolismo , Fatores de Tempo
20.
Int J Nanomedicine ; 16: 3173-3183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34007172

RESUMO

Aim: Cerebral ischemic injury is one of the debilitating diseases showing that inflammation plays an important role in worsening ischemic damage. Therefore, studying the effects of some potential anti-inflammatory compounds can be very important in the treatment of cerebral ischemic injury. Methods: This study investigated anti-inflammatory effects of triblock copolymer nanomicelles loaded with curcumin (abbreviated as NC) in the brain of rats following transient cerebral ischemia/reperfusion (I/R) injury in stroke. After preparation of NC, their protective effects against bilateral common carotid artery occlusion (BCCAO) were explored by different techniques. Concentrations of free curcumin (C) and NC in liver, kidney, brain, and heart organs, as well as in plasma, were measured using a spectrofluorometer. Western blot analysis was then used to measure NF-κB-p65 protein expression levels. Also, ELISA assay was used to examine the level of cytokines IL-1ß, IL-6, and TNF-α. Lipid peroxidation levels were assessed using MDA assay and H&E staining was used for histopathological examination of the hippocampus tissue sections. Results: The results showed a higher level of NC compared to C in plasma and organs including the brain, heart, and kidneys. Significant upregulation of NF-κB, IL-1ß, IL-6, and TNF-α expressions compared to control was observed in rats after induction of I/R, which leads to an increase in inflammation. However, NC was able to downregulate significantly the level of these inflammatory cytokines compared to C. Also, the level of lipid peroxidation in pre-treated rats with 80mg/kg NC was significantly reduced. Conclusion: Our findings in the current study demonstrate a therapeutic effect of NC in an animal model of cerebral ischemia/reperfusion (I/R) injury in stroke through the downregulation of NF-κB-p65 protein and inflammatory cytokines.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Inflamação/tratamento farmacológico , Micelas , NF-kappa B/metabolismo , Nanopartículas/química , Polímeros/química , Transdução de Sinais , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Curcumina/farmacologia , Citocinas/sangue , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Inflamação/complicações , Inflamação/patologia , Lactatos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Nanopartículas/ultraestrutura , Fosforilação/efeitos dos fármacos , Polietilenoglicóis/química , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Distribuição Tecidual/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
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