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1.
Mater Sci Eng C Mater Biol Appl ; 119: 111649, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33321685

RESUMO

The interaction of nanoparticles with protein and cells may provide important information regarding their biomedical implementations. Herein, after synthesis of tin oxide (SnO2) nanoparticles by hydrothermal method, their interaction with human serum albumin (HSA) was evaluated by multispectroscopic and molecular docking (MD) approaches. Furthermore, the selective antiproliferative impact of SnO2 nanoparticles against leukemia K562 cells was assessed by different cellular assays, whereas lymphocytes were used as control cells. TEM, DLS, zeta potential and XRD techniques showed that crystalline SnO2 nanoparticles have a size of less than 50 nm with a good colloidal stability. Fluorescence and CD spectroscopy analysis indicated that the HSA undergoes some slight conformational changes after interaction with SnO2 nanoparticles, whereas the secondary structure of HSA remains intact. Moreover, MD outcomes revealed that the charged residues of HSA preferentially bind to SnO2 nanoclusters in the binding pocket. Antiproliferative examinations displayed that SnO2 nanoparticles can selectively cause the mortality of K562 cells through induction of cell membrane leakage, activation of caspase-9, -8, -3, down regulation of Bcl-2 mRNA, the elevation of ROS level, S phase arrest, and apoptosis. In conclusion, this data may indicate that SnO2 nanoparticles can be used as promising particles to be integrated into therapeutic platforms.


Assuntos
Nanopartículas , Compostos de Estanho , Humanos , Células K562 , Simulação de Acoplamento Molecular
2.
J Biomol Struct Dyn ; 38(12): 3676-3686, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31476976

RESUMO

Nickel oxide nanoparticles (NiO NPs) have received great interests in medical and biotechnological applications. However, their adverse impacts against biological systems have not been well-explored. Herein, the influence of NiO NPs on structural changes, heme degradation and aggregation of hemoglobin (Hb) was evaluated by UV-visible (Vis) spectroscopy, circular dichroism (CD) spectroscopy, fluorescence spectroscopy, transmission electron microscopy (TEM), and molecular modeling investigations. Also, the morphological changes and expression of Bax/Bcl-2 mRNA in human lymphocyte cell exposed to NiO NPs were assayed by DAPI staining and quantitative real-time PCR (qPCR), respectively. The UV-Vis study depicted that NiO NPs resulted in the displacement of aromatic residues and heme groups and production of the pro-aggregatory species. Intrinsic and Thioflavin T (ThT) fluorescence studies revealed that NiO NPs resulted in heme degradation and amorphous aggregation of Hb, respectively, which the latter result was also confirmed by TEM study. Moreover, far UV-CD study depicted that NiO NPs lead to substantial secondary structural changes of Hb. Furthermore, near UV-CD displayed that NiO NPs cause quaternary conformational changes of Hb as well as heme displacement. Molecular modelling study also approved that NiO NPs resulted in structural alterations of Hb and heme deformation. Moreover, morphological and genotoxicity assays revealed that the DNA fragmentation and expression ratio of Bax/Bcl-2 mRNA increased in lymphocyte cells treated with NiO NPs for 24 hr. In conclusion, this study indicates that NiO NPs may affect the biological media and their applications should be limited.Communicated by Ramaswamy H. Sarma.


Assuntos
Apoptose , Linfócitos , Nanopartículas Metálicas/toxicidade , Níquel/toxicidade , Heme , Hemoglobinas , Humanos
3.
Eur J Pharmacol ; 865: 172757, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31693870

RESUMO

Family, adoption and twin studies have highlighted the significant role of heritable influences on individual differences in opioid addiction. Meanwhile, obsessive-compulsive disorder (OCD) is a disorder wherein the individual experiences recurring thoughts that cause irrational fears and anxiety. In the present study, adult male and female rats received morphine solution for 21 days and were drug-free for 10 days. Offspring were used in 4 distinct groups; (1) paternal morphine-exposed, (2) maternal morphine-exposed, (3) maternal and paternal morphine-exposed, and (4) drug-naïve subjects. We assessed the grooming behavior and marble burying test as an indicator of obsessive-compulsive behavior. To clarify the mechanisms underlying these changes, the mRNA level of BDNF, the phosphorylation level of CREB and the protein level of D2 dopamine receptor (DR) were evaluated in the nucleus accumbens (NAc). The grooming behavior in male offspring with one or two morphine-abstinent parent(s) increased compared with the offspring of drug naïve rats. In addition, the offspring of morphine-exposed parents buried more marbles when compared with the offspring of drug-naïve parents. Also, the BDNF mRNA was down-regulated in the NAC. However, the levels of phospho-CREB and D2 DR were elevated. Previous studies indicated that exposure to morphine in adulthood enhances the risk of psychiatric disorders in offspring. OCD is one the comorbid disorders with addiction and increases the risk of substance abuse disorder in patients. In this survey, we found that morphine exposure in parents before gestation can encourage obsessive-compulsive behavior in offspring.


Assuntos
Analgésicos Opioides/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Comportamento Compulsivo/induzido quimicamente , Morfina/efeitos adversos , Transtorno Obsessivo-Compulsivo/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Comportamento Compulsivo/metabolismo , Modelos Animais de Doenças , Feminino , Asseio Animal/efeitos dos fármacos , Masculino , Troca Materno-Fetal , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Transtorno Obsessivo-Compulsivo/metabolismo , Gravidez , Ratos Wistar , Receptores de Dopamina D2/metabolismo
4.
Int J Nanomedicine ; 14: 5355-5368, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409992

RESUMO

Aim: Nanoparticles (NPs) have been receiving potential interests in protein delivery and cell therapy. As a matter of fact, NPs may be used as great candidates in promoting cell therapy by catalase (CAT) delivery into high oxidative stress tissues. However, for using NPs like SiO2 as carriers, the interaction of NPs with proteins and mesenchymal stem cells (MSCs) should be explored in advance. Methods: In the present study, the interaction of SiO2 NPs with CAT and human MSCs (hMSCs) was explored by various spectroscopic methods (fluorescence, circular dichroism (CD), UV-visible), molecular docking and dynamics studies, and cellular (MTT, cellular morphology, cellular uptake, lactate dehydrogenase, ROS, caspase-3, flow cytometry) assays. Results: Fluorescence study displayed that both dynamic and static quenching mechanisms and hydrophobic interactions are involved in the spontaneous interaction of SiO2 NPs with CAT. CD spectra indicated that native structure of CAT remains stable after interaction with SiO2 NPs. UV-visible study also revealed that the kinetic parameters of CAT such as Km, Vmax, Kcat, and enzyme efficiency were not changed after the addition of SiO2 NPs. Molecular docking and dynamics studies showed that Si and SiO2 clusters interact with hydrophobic residues of CAT and SiO2 cluster causes minor changes in the CAT structure at a total simulation time of 200 ps. Cellular assays depicted that SiO2 NPs induce significant cell mortality, change in cellular morphology, cellular internalization, ROS elevation, and apoptosis in hMSCs at higher concentration than 100 µg/mL (170 µM). Conclusion: The current results suggest that low concentrations of SiO2 NPs induce no substantial change or mortality against CAT and hMSCs, and potentially useful carriers in CAT delivery to hMSC.


Assuntos
Fenômenos Biofísicos , Células-Tronco Mesenquimais/citologia , Modelos Teóricos , Nanopartículas/química , Dióxido de Silício/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Catalase/metabolismo , Forma Celular/efeitos dos fármacos , Dicroísmo Circular , Endocitose/efeitos dos fármacos , Humanos , Cinética , L-Lactato Desidrogenase/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Fluorescência , Termodinâmica
5.
Int J Biol Macromol ; 127: 330-339, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30654034

RESUMO

Herein, the thermodynamic parameters of tau upon interaction with NiO NPs were determined by fluorescence spectroscopy. Also, molecular docking studies were run to explore the binding affinities of NiO NPs clusters with different sizes of 30 Šand 50 Štoward tau. Also, cytotoxic activity of NiO NPs against SH-SY5Y was determined by MTT, LDH, caspase-9/3 activity, and expression of apoptotic Bax and Bcl-2 genes assays. DLS study showed that NiO solution had a good colloidal stability. Fluorescence study revealed that KSV values were 2.95 ±â€¯0.35 × 104, 3.31 ±â€¯0.59 × 104 and 3.92 ±â€¯0.65 × 104 at 298 K, 310 K and 315 K, respectively. Also, ∆G° (kJ/mol), ∆H° (kJ/mol) and T∆S° (kJ/mol) values were - 13.27 ±â€¯1.57, 1.98 ±â€¯0.14, 15.25 ±â€¯2.01, respectively at 298 K. Theoretical studies depicted that affinity of 5O3T segment toward NiO NP (30 Å) is higher than NiO NP (50 Å) and the proportion of Lys residues are higher in the docked pose of NiO NP (30 Å)/5O3T complex than NP (50 Å)/5O3T complex. Moreover, NiO NPs demonstrated a significant increase in the mortality of SH-SY5Y cells in an apoptotic manner. This study determined that NiO NPs may mediate the formation of electrostatic interactions with tau and induction of undesired harmful effects on neurons.


Assuntos
Apoptose/efeitos dos fármacos , Nanopartículas/química , Neurônios/metabolismo , Proteínas tau/metabolismo , Animais , Linhagem Celular , Neurônios/patologia , Níquel/química , Níquel/farmacologia , Ratos
6.
Int J Biol Macromol ; 125: 674-682, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30468808

RESUMO

Manganese oxide nanoparticles (Mn2O3 NPs) have been widely used in the medical and biological applications. However, few studies have been undertaken to investigate the cytotoxicity of Mn2O3 NPs against nervous system. Herein, we studied the toxicity of Mn2O3 NPs against tau protein and neuroblastoma cells (SH-SY5Y) in vitro. Circular dichroism (CD) spectroscopy, fluorescence spectroscopy, molecular docking, and molecular dynamic studies were used to explore the conformational changes of protein. The cell-based experiments, such as viability, activation of caspases-3/9, apoptosis, and gene (Bax and Bcl-2) expression assays were performed in vitro. Spectroscopic methods and molecular dynamic studies revealed that Mn2O3 NPs can fold the structure of tau toward a more packed structure. The Mn2O3 NPs also decreased the cell viability in a dose-dependent manner. Indeed, caspase-3 and caspase-9 activation, Bax/Bcl-2 ratio elevation and apoptosis induction were observed after exposure of SH-SY5Y to Mn2O3 NPs. In conclusion, tau folding and cytotoxicity against SH-SY5Y cells may be involved in adverse effects induced by Mn2O3 NPs.


Assuntos
Compostos de Manganês/efeitos adversos , Nanopartículas Metálicas/efeitos adversos , Neuroblastoma/metabolismo , Óxidos/efeitos adversos , Dobramento de Proteína/efeitos dos fármacos , Proteínas tau/metabolismo , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular/métodos , Humanos , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
7.
Brain Res Bull ; 144: 122-131, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30503221

RESUMO

It has been proven that exposure to some drugs even before gestation had transgenerational effects. To investigate the changes which induced by parental morphine exposure before gestation; mainly the anxiety-like behavior, Corticotropin Releasing Factor (CRF) level in the CSF and plasma, CRF Receptor 1 (CRFR1), and the level of protein kinase C (PKC-α) were evaluated in the male offspring. Male and female Wistar rats were exposed to morphine for 21 following days. Ten days after last drug exposure, animals were prepared for mating in 4 distinct groups as follow: drug-naïve female and male (used as control), drug-naïve female and morphine-abstinent male, drug-naïve male and morphine-abstinent female, and morphine abstinent male and female. Offspring were subjected to assess anxiety-like behavior (using elevated plus maze test). CSF and plasma were gathered, and the CRF level was evaluated by ELISA. Using real-time PCR, the CRFR1 level in the brain was evaluated. Results showed that anxiety-like behavior increased in the offspring of morphine-abstinent parent(s) compared with the control group. CRF level in the plasma and CSF also increased in the litter of morphine-abstinent parent(s). CRFR1 mRNA level was upregulated in the brain of offspring with one and/or two morphine-abstinent parent(s). Furthermore, the level of PKC-α was decreased in the brain of offspring which had one and/or two morphine-abstinent parent(s). Taken together, our findings indicated that morphine exposure even before gestation induced transgenerational effects via dysregulation of HPA axis which results in anxiety in the adult male offspring.


Assuntos
Exposição Materna/efeitos adversos , Morfina/efeitos adversos , Animais , Ansiedade/etiologia , Ansiedade/metabolismo , Hormônio Liberador da Corticotropina/análise , Hormônio Liberador da Corticotropina/sangue , Hormônio Liberador da Corticotropina/líquido cefalorraquidiano , Feminino , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Entorpecentes/efeitos adversos , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Proteína Quinase C/análise , Proteína Quinase C/metabolismo , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/análise , Receptores de Hormônio Liberador da Corticotropina/metabolismo
8.
J Trace Elem Med Biol ; 29: 242-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25084733

RESUMO

PROJECT: Cholestasis liver fibrosis has been increasingly recognized as a cause of high morbidity and mortality in humans. The accumulation of toxic bile salts in a bile duct ligation (BDL) animal model plays a pivotal role in the induction of liver fibrosis. Cholestatic liver fibrosis is characterized by excessive collagen production and deposition, which is mediated by reactive oxygen species (ROS). Molybdenum is an essential micronutrient trace element which acts as a cofactor in many detoxification system enzymes. The aim of the present study was to evaluate the antifibrotic effect of sodium molybdate on liver cholestasis induced by bile duct ligation in rats. PROCEDURE: After BDL, rats were given sodium molybdate (0.05 or 0.1 or 0.2g/kg) or urosodeoxycholic acid (UDCA, 25mg/kg) via intragastric gavage for 45 consecutive days (once per day). RESULTS: BDL drastically increased the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin and direct bilirubin, whereas it reduced the levels of antioxidant enzymes, superoxide dismutase and catalase in the liver. Treatment of BDL rats with sodium molybdate significantly attenuated these changes. As determined by Masson's trichrome staining, BDL markedly induced the liver fibrosis. These alterations were also significantly attenuated by sodium molybdate administration. CONCLUSIONS: The results of this study indicate the hepatoprotective and antifibrotic effect of sodium molybdate in the cholestatic liver. Sodium molybdate, by inhibiting the activation of Ito cells, decreases the collagen production in the liver. The antifibrotic effect of sodium molybdate is likely due to the antioxidative and free radical scavenging effects of this trace element.


Assuntos
Ductos Biliares/patologia , Cirrose Hepática/tratamento farmacológico , Fígado/patologia , Molibdênio/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Antioxidantes/metabolismo , Ductos Biliares/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Ligadura , Fígado/efeitos dos fármacos , Fígado/enzimologia , Cirrose Hepática/sangue , Masculino , Molibdênio/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar
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