RESUMO
Bio-inspired zinc oxide nanoparticles are gaining immense interest due to their safety, low cost, biocompatibility, and broad biological properties. In recent years, much research has been focused on plant-based nanoparticles, mainly for their eco-friendly, facile, and non-toxic character. Hence, the current study emphasized a bottom-up synthesis of zinc oxide nanoparticles (ZnO NPs) from Psidium guajava aqueous leaf extract and evaluation of its biological properties. The structural characteristic features of biosynthesized ZnO NPs were confirmed using various analytical methods, such as UV-Vis spectroscopy, X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDX), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), Scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HR-TEM). The synthesized ZnO NPs exhibited a hydrodynamic shape with an average particle size of 11.6-80.2 nm. A significant antimicrobial efficiency with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 40 and 27 µg/ml for Enterococcus faecalis, followed by 30 and 40 µg/ml for Staphylococcus aureus, 20 and 30 µg/ml for Staphylococcus mutans, 30 µg/ml for Candida albicans was observed by ZnO NPs. Additionally, they showed significant breakdown of biofilms of Streptococcus mutans and Candida albicans indicating their future value in drug-resistance research. Furthermore, an excellent dose-dependent activity of antioxidant property was noticed with an IC50 of 9.89 µg/ml. The antiproliferative potential of the ZnO NPs was indicated by the viability of MDA MB 231 cells, which showed a drastic decrease in response to increased concentrations of biosynthesized ZnO NPs. Thus, the present results open up vistas to explore their pharmaceutical potential for the development of targeted anticancer drugs in the future.
Assuntos
Antioxidantes , Nanopartículas Metálicas , Psidium , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Psidium/química , Antioxidantes/farmacologia , Antioxidantes/química , Nanopartículas Metálicas/química , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/crescimento & desenvolvimento , Antibacterianos/farmacologia , Antibacterianos/química , Folhas de Planta/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Nanopartículas/químicaRESUMO
Epidemiological studies have shown associations between prenatal exposure to lead (Pb) and neurodevelopmental effects in young children. Prenatal exposure is generally characterized by measuring the concentration in the umbilical cord at delivery or in the maternal blood during pregnancy. To assess internal Pb exposure during prenatal life, we developed a pregnancy physiologically based pharmacokinetic (p-PBPK) model that to simulates Pb levels in blood and target tissues in the fetus, especially during critical periods for brain development. An existing Pb PBPK model was adapted to pregnant women and fetuses. Using data from literature, both the additional maternal bone remodeling, that causes Pb release into the blood, and the Pb placental transfers were estimated by Bayesian inference. Additional maternal bone remodeling was estimated to start at 21.6 weeks. Placental transfers were estimated between 4.6 and 283 L.day-1 at delivery with high interindividual variability. Once calibrated, the p-PBPK model was used to simulate fetal exposure to Pb. Internal fetal exposure greatly varies over the pregnancy with two peaks of Pb levels in blood and brain at the end of the 1st and 3rd trimesters. Sensitivity analysis shows that the fetal blood lead levels are affected by the maternal burden of bone Pb via maternal bone remodeling and by fetal bone formation at different pregnancy stages. Coupling the p-PBPK model with an effect model such as an adverse outcome pathway could help to predict the effects on children's neurodevelopment.
Assuntos
Chumbo , Efeitos Tardios da Exposição Pré-Natal , Criança , Humanos , Gravidez , Feminino , Pré-Escolar , Chumbo/toxicidade , Gestantes , Placenta/metabolismo , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Toxicocinética , Teorema de Bayes , Osso e Ossos/metabolismo , Troca Materno-Fetal , Modelos BiológicosRESUMO
OBJECTIVE: The study investigated the effects of haloperidol on peripheral erythrocytes and brain neurotransmitter levels of juvenile African Sharptooth Catfish Clarias gariepinus. METHODS: Juveniles were exposed to different concentrations of haloperidol (0.12, 0.24, and 0.48 mg/L) for 15 days and subsequently withdrawn from the drug for 5 days. Blood samples from the fish on days 1, 5, 10, and 15 and after the 5-day withdrawal period were analyzed for mutagenic changes, after which the fish were sacrificed. The brain was sampled for serotonergic and dopaminergic analyses. RESULT: There was formation of micronuclei in the peripheral fish blood, which increased as the duration and concentrations of the drug increased. The drug significantly reduced the serotonin activity but increased dopamine activity. Some of the studied parameters, however, recovered from the effects of the drug after the 5-day withdrawal period. CONCLUSION: Haloperidol is toxic to fish, and its use in the environment should be guarded to avoid adverse impacts on nontarget species like fish.
Assuntos
Peixes-Gato , Poluentes Químicos da Água , Animais , Haloperidol/farmacologia , Eritrócitos , EncéfaloRESUMO
Lead (Pb) is a non-essential metal with high toxicity, is persistent, is not biodegradable, and has no known biological function. It is responsible for severe health and environmental issues that need appropriate remediation. Therefore, microbes have thrived in a lead-contaminated environment without exhibiting any negative impacts. The present study aimed to examine the toxic effects of lead on animals and the isolation, identification, and characterization of lead-resistant bacterial strains and their biodegradation potential. After oral administration of lead for 4 weeks, mice showed an elevated level of leukocytes and a decrease in TEC, Hb, PCV, MCV, MCH, and MCHC levels. However, a decline in body weight and inflammation and oxidative stress was observed in liver tissues. To remediate toxic heavy metal, lead-resistant bacterial strains were isolated, among which Enterobacter exhibited maximum degradation potential at high lead concentrations. It was identified by molecular basis and after 16S rRNA sequencing, and 99% resemblance was observed with Enterobacter cloacae. FT-IR analysis of the bacteria illustrated the presence of functional groups, including hydroxyl, carboxyl group, sulfide, and amino groups, on the bacterial cell surface involved in the adsorption of lead. Moreover, electron microscopy (SEM) revealed the morphological and physiochemical changes in the bacterial cell after biosorption, indicating the interaction of Cu ions with functional groups. To summarize, the findings show the highly toxic effects of lead on animals and humans and its effective biodegradation by the bacterial strains in the lead-contaminated environment. This biological strategy can be an ideal alternative to remediate heavy metals from contaminated sites to clean up the environment.
Assuntos
Chumbo , Metais Pesados , Humanos , Animais , Camundongos , Biodegradação Ambiental , RNA Ribossômico 16S , Espectroscopia de Infravermelho com Transformada de Fourier , Monitoramento Ambiental , Metais Pesados/toxicidadeRESUMO
New advancements of photocatalytic activity with higher efficiency, low price are most important, which is challenging in industrialized and many fields. We have introduced CuNiO2 and CuNiO2/rGO nanocomposite was generally prepared by the hydrothermal treatment and tested to the photocatalytic studies. Photocatalytic measurements of CuNiO2 with different weight percentages CuNiO2/rGO (25/75), (50/50), and (75/25) are achieved to the efficiency under visible light, in this case, CuNiO2/rGO (50/50) composite have the highest performance is scrutinized. This was obeyed for a synergistic effect between CuNiO2 nanoparticles and rGO composites. Furthermore, the CuNiO2, CuNiO2/rGO (25/75), (50/50), and (75/25) nanocomposite were tested by several analyses like XRD, FT-IR, DRS UV Visible spectroscopy, Raman spectroscopy, and FESEM & HRTEM investigations. In this regard all measurements are very clear and satisfied; therefore we are encouraged for future developing environmental applications.
Assuntos
Azul de Metileno , Nanocompostos , Catálise , Grafite , Azul de Metileno/química , Nanocompostos/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
5-fluorouracil (5FU) is widely used to treat colorectal cancer (CC) and its main mechanisms of anticancer action are through generation of ROS which often result in inflammation. Here, we test the effect of Lycopene against 5FU in Caco2 cell line. Caco2 cells were exposed to 3 µg/ml of 5FU alone or with 60, 90, 120 µg/ml of lycopene. This was followed by assessment of cytotoxicity, oxidative stress, and gene expression of inflammatory genes. Our findings showed that Lycopene and 5FU co-exposure induced dose-dependent cytotoxic effect without compromising the membrane integrity based on the LDH assay. Lycopene also significantly enhanced 5FU-induced SOD activity and GSH level compared to control for all mixture concentrations (p < 0.01). Lycopene alone and combination with 5FU-induced expression of IL-1ß, TNF-α, and IL-6. Furthermore, IFN-γ expression was significantly enhanced by only mixture of lycopene (90 µg/ml) and 5FU (p < 0.05). In conclusion, Lycopene supplementation with 5FU therapy resulted in improvement in antioxidant parameters such as catalase and GSH levels giving the cell capacity to cope with 5FU-mediated oxidative stress. Lycopene also enhanced IFN-γ expression in the presence of 5FU, which may activate antitumor effects further enhancing the cancer killing effect of 5FU.
RESUMO
Multi-walled carbon nanotubes (MWCNTs) have many applications in industry and used as additives in polymers, catalysts, anodes in lithium-battery and drug delivery. There is little information about MWCNTs' (210 nm) genotoxic potential on juvenile freshwater fish Channa punctatus. Therefore, in this study, we have determined the toxic effects of MWCNTs on freshwater fish C. punctatus by assessing toxicological endpoints such as oxidative stress, mutagenicity, and genotoxicity after acute MWCNTs exposure for 5 days. MWCNTs LC50 -96 hours value for C. punctatus was 21.8 mg/L and on this basis three different MWCNTs concentrations were selected, that is, sub-lethal I, II, and III, for 5-days exposure trials with C. punctatus. The level of lipid peroxidation increased in the gills and kidney of exposed fish at sub-lethal concentrations II and III. Contrastingly, glutathione decreased more in the gills than in the kidney. The activity of catalase enzymes decreased more in the gills than in the kidney at sublethal concentrations I and II. Glutathione S-transferase decreased in gill tissue but increased in kidney tissue following sub-lethal III exposure. Moreover, the level of glutathione reductase decreased in both tissues. In addition, MWCNTs genotoxicity was confirmed by DNA damage in lymphocytes, gills, kidney cells, and production of micronuclei (MNi) in red blood cells of freshwater fish following sub-lethal I, II, and III exposures. In conclusion, this study revealed that application of micronucleus and comet assays for in vivo laboratory studies using freshwater fish for screening the genotoxic potential of MWCNTs.
Assuntos
Dano ao DNA , Peixes , Nanotubos de Carbono/toxicidade , Estresse Oxidativo , Animais , Ensaio Cometa , Peixes/genética , Peixes/crescimento & desenvolvimento , Peixes/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Glutationa/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Testes para Micronúcleos , Mutagênicos/toxicidadeRESUMO
Platinum nanoparticles (PtNPs) attract much attention due to their excellent biocompatibility and catalytic properties, but their toxic effects on normal (CHANG) and cancerous (HuH-7) human liver cells are meagre. The cytotoxic and apoptotic effects of PtNPs (average size, 3 nm) were determined in CHANG and HuH-7 cells. After treating these cells were with PtNPs (10, 50, 100, 200, and 300 µg/mL) for 24 and 48 hours, we observed dose- and time-dependent cytotoxicity, as evaluated by using (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, a tetrazole) (MTT) and neutral red uptake (NRU) assays. The production of reactive oxygen species (ROS) was increased in both cells after treatment with the above dose of PtNPs for 24 and 48 hours. Determination of morphological changes of cells, chromosome condensation, mitochondrial membrane potential, and caspase-3 assays showed that PtNPs induce cytotoxicity and apoptosis in CHANG and HuH-7 cells by altering the cell morphology and density, increasing cell population in apoptosis, and causing chromosome condensation. Furthermore, we have studied fragmentation of DNA using alkaline single cell gel electrophoresis and expression of apoptotic genes by real-time PCR (RT-PCR). The percentage of DNA fragmentation was more at 300 µg/mL for 48 hours in both cells, but slightly more fragmentation was found in HuH-7 relative to CHANG cells. Considering all of the above parameters, PtNPs elicited cytotoxicity on CHANG and HuH-7 cells by blocking cell proliferation and inducing apoptosis. Thus this study may be useful in in vitro laboratory studies using cell lines for screening the genotoxic and apoptotic potential of nanoparticles.
Assuntos
Apoptose/efeitos dos fármacos , Dano ao DNA , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Platina/farmacologia , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Morte Celular , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Humanos , Fígado/metabolismo , Fígado/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/genética , Platina/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
This study aimed to evaluate the potential neuroprotective effect of royal jelly (RJ) against Cd-induced neuronal damage. Twenty-eight adult mice were placed equally into four groups. The control group received intraperitoneal (IP) injections of normal saline; the cadmium chloride (CdCl2) group was IP-injected 6.5 mg/kg (mg per kg of bodyweight) CdCl2; the RJ group was gavaged 85 mg/kg RJ; and the RJ + CdCl2 group was orally administered 85 mg/kg RJ 2 h before receiving IP-injections of 6.5 mg/kg CdCl2. All groups were treated for seven consecutive days and the mice were decapitated 24 h after the final dose. Cd accumulation was recorded in the cortical homogenates, accompanied by elevated levels of lipid peroxidation, nitric oxide, tumor necrosis factor-α, interleukin-1ß, and the pro-apoptotic mRNA Bax and caspase-3. Meanwhile, significantly decreased levels of detoxifying antioxidant enzymes including GSH-Px, GSH-R, SOD, and CAT, anti-apoptotic mRNA Bcl-2, and monoamines such as norepinephrine, dopamine, and serotonin were also observed, along with reduced gene expression of Nrf2-dependent antioxidants. Interestingly, in mice pretreated with RJ, the assessed parameters remained near normal levels. Our data provide evidence that RJ treatment has the potential to protect cortical neurons in Cd-intoxicated mice via its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory activity.
Assuntos
Ácidos Graxos/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cádmio/efeitos adversos , Cádmio/farmacologia , Cloreto de Cádmio/metabolismo , Ácidos Graxos/metabolismo , Interleucina-1beta/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Neurônios/metabolismo , Fármacos Neuroprotetores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
The current study examined the efficacy of royal jelly (RJ) against cadmium chloride (CdCl2)-induced testicular dysfunction. A total of 28 Swiss male mice were allocated into four groups (n = 7), and are listed as follows: (1) the control group, who was intraperitoneally injected with physiological saline (0.9% NaCl) for 7 days; (2) the RJ group, who was orally supplemented with RJ (85 mg/kg daily equivalent to 250 mg crude RJ) for 7 days; (3) the CdCl2 group, who was intraperitoneally injected with 6.5 mg/kg for 7 days; and (4) the fourth group, who was supplemented with RJ 1 h before CdCl2 injection for 7 days. Cd-intoxicated mice exhibited a decrease in serum testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. A disturbance in the redox status in the testicular tissue was recorded, as presented by the increase in lipid peroxidation and nitrate/nitrite levels and glutathione (GSH) depletion. Moreover, the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and nuclear factor (erythroid-derived 2)-like-2 factor (Nrf2) and their gene expression were inhibited. In addition, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels were elevated. Furthermore, Cd triggered an apoptotic cascade via upregulation of caspase-3 and Bax and downregulation of Bcl-2. Histopathological examination showed degenerative changes in spermatogenic cells, detachment of the spermatogenic epithelium from the basement membrane, and vacuolated seminiferous tubules. Decreased cell proliferation was reflected by a decrease in proliferating cell nuclear antigen (PCNA) expression. Interestingly, RJ supplementation markedly minimized the biochemical and molecular histopathological changes in testes tissue in response to Cd exposure. The beneficial effects of RJ could be attributed to its antioxidative properties.
Assuntos
Cádmio/toxicidade , Ácidos Graxos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Animais , Apoptose/efeitos dos fármacos , Ácidos Graxos/administração & dosagem , Hormônio Foliculoestimulante/sangue , Glutationa/metabolismo , Inflamação/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Hormônio Luteinizante/sangue , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , Nitratos/metabolismo , Nitritos/metabolismo , Tamanho do Órgão/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Testículo/efeitos dos fármacos , Testosterona/sangueRESUMO
Mammalian studies have raised concerns about the toxicity of carbon nanotubes, but there is very limited data on ecogenotoxicity to aquatic organisms. The aim of this study was to determine eco-geno toxic effects of single walled carbon nanotubes (SWCNTs) in fresh water snail, Lymnea luteola (L. luteola). A static test system was used to expose L. luteola to a freshwater control, 0.05, 0.15, 0.30, 0.46 mg/L SWCNTs for up to 4 days. SWCNTs changed a significant reduction in glutathione, glutathione-S-transferase, and glutathione peroxidase with in hepatopancreas of L. luteola. Lipid peroxidation (LPO) and catalase showed dose- and time-dependent and statistically significant increase in hepatopancreas during SWCNTs exposure compared with control. However, a significant (p < 0.01) induction in DNA damage was observed by the comet assay in hepatopancreas cells treated with SWCNTs. These results demonstrate that SWCNTs are ecogenotoxic to freshwater snail L. luteola. The oxidative stress and comet assay can successfully be used as sensitive tools of aquatic pollution biomonitoring.
Assuntos
Lymnaea/efeitos dos fármacos , Mutagênicos/toxicidade , Nanotubos de Carbono/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Comportamento Animal , Catalase/metabolismo , Ensaio Cometa , Dano ao DNA , Água Doce , Glutationa/metabolismo , Glutationa Peroxidase , Hemolinfa/efeitos dos fármacos , Hepatopâncreas/patologia , Dose Letal Mediana , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Silver nanoparticles are increasingly used in various products, due to their antibacterial properties. Despite its wide spread use, only little information on possible adverse health effects exists. Therefore, the aim of this study was to assess the toxic potential of silver nanoparticles (<100 nm) in human lung epithelial (A549) cells and the underlying mechanism of its cellular toxicity. Silver nanoparticles induced dose and time-dependent cytotoxicity in A549 cells demonstrated by MTT and LDH assays. Silver nanoparticles were also found to induce oxidative stress in dose and time-dependent manner indicated by depletion of GSH and induction of ROS, LPO, SOD, and catalase. Further, the activities of caspases and the level of proinflammatory cytokines, namely interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were significantly higher in treated cells. DNA damage, as measured by single cell gel electrophoresis, was also dose and time-dependent signicants in A549 cells. This study investigating the effects of silver nanoparticles in human lung epithelial cells has provided valuable insights into the mechanism of potential toxicity induced by silver nanoparticles and warrants more careful assessment of silver nanoparticles before their industrial applications.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Inflamação/induzido quimicamente , Nanopartículas Metálicas/toxicidade , Mutagênicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Prata/toxicidade , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Linhagem Celular , Humanos , Inflamação/patologia , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Mutagenicidade , Espécies Reativas de Oxigênio/metabolismo , Mucosa Respiratória/citologiaRESUMO
The extensive production and wide application of carbon nanotubes have made investigations of its toxic potentials necessary. In the present study, we explored the underlying mechanism through which multi-walled carbon nanotubes (MWCNTs) induce toxicity in mouse fibroblast cells (L929). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and neutral red uptake viability assays were used to examine mechanisms of cytotoxicity. Dose and time-dependent cytotoxicity was observed in L929 cells. The MWCNTs significantly increased the generation of reactive oxygen species, lipid peroxidation, superoxide dismutase, and decreased glutathione. It was observed that the MWCNTs induced caspase 3 activity. The highest DNA strand breakage was detected by comet assay at 300 µg/mL of MWCNTs. Thus, the data indicate that MWCNTs induced cytotoxicity and apoptosis in L929 cells via oxidative stress.
Assuntos
Apoptose/efeitos dos fármacos , Quebras de DNA , Fibroblastos/efeitos dos fármacos , Mutagênicos/toxicidade , Nanotubos de Carbono/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Caspase 3/química , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Fibroblastos/citologia , Fibroblastos/metabolismo , Glutationa/antagonistas & inibidores , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Microscopia Eletrônica de Transmissão , Mutagênicos/química , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
The apoptotic and genotoxic potential of titanium dioxide nanoparticles (TiO2NPs) were evaluated in hemocyte cells of freshwater snail Lymnea luteola L. Before evaluation of the toxic potential, mean size of the TiO2NPs was determined using a transmission electron microscopy and dynamic light scattering. In this study, L. luteola were exposed to different concentrations of TiO2NPs (28, 56, and 84 µg/ml) over 96 h. Induction of oxidative stress in hemolymph was observed by a decrease in reduced glutathione and glutathione-S-transferase levels at different concentration of TiO2NPs and, in contrast, an increase in malondialdehyde and reactive oxygen species levels. Catalase activity was decreased at lower concentrations but increased at greater concentration of TiO2NPs. The extent of DNA fragmentation occurring in L. luteola due to ecotoxic impact TiO2NPs was further substantiated by alkaline single-cell gel electrophoresis assay and expressed in terms of % tail DNA and olive tail moment. The alkaline single-cell gel electrophoresis assay for L. luteola clearly shown relatively greater DNA damage at the highest concentration of TiO2NPs.The results indicate that the interaction of TiO2NPs with snail influences toxicity, which is mediated by oxidative stress according dose and in a time-dependent manner. The results of this study showed the importance of a multibiomarker approach for assessing the injurious effects of TiO2NPs to freshwater snail L. luteola, which may be vulnerable due to the continuous discharge of TiO2NPs into the aquatic ecosystems. The measurement of DNA integrity in L. luteola thus provides an early warning signal of contamination of the aquatic ecosystem by TiO2NPs.
Assuntos
Dano ao DNA , Lymnaea/fisiologia , Nanopartículas/toxicidade , Titânio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Água Doce , Glutationa/metabolismo , Microscopia Eletrônica de TransmissãoRESUMO
Fluorescence monitoring of endogenous microRNA (miRNA or miR) activity related to neuronal development using nano-sized materials provides crucial information on miRNA expression patterns in a noninvasive manner. In this study, we report a new method to monitor intracellular miRNA124a using quantum dot-based molecular beacon (R9-QD-miR124a beacon). The R9-QD-miR124a beacon was constructed using QDs and two probes, miR124a-targeting oligomer and arginine rich cell-penetrating peptide (R9 peptide). The miR124a-targeting oligomer contains a miR124a binging sequence and a black hole quencher 1 (BHQ1). In the absence of target miR124a, the R9-QD-miR124a beacon forms a partial duplex beacon and remained in quenched state because the BHQ1 quenches the fluorescence signal of the R9-QD-miR124a beacon. The binding of miR124a to the miR124a binding sequence of the miR124a-targeting oligomer triggered the separation of the BHQ1 quencher and subsequent signal-on of a red fluorescence signal. Moreover, enhanced cellular uptake was achieved by conjugation with the R9 peptide, which resulted in increased fluorescent signal of the R9-QD-miR124a beacons in P19 cells during neurogenesis due to the endogenous expression of miR124a.
Assuntos
Espaço Intracelular/química , MicroRNAs/análise , MicroRNAs/química , Imagem Molecular/métodos , Pontos Quânticos/química , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes , Camundongos , Neurogênese/fisiologia , Peptídeos/químicaRESUMO
The issue of antibiotic resistance in pathogenic microbes is a global concern. This study was aimed to explore in silico and in vitro analysis of the antibacterial efficacy of different natural ligands against bacterial activity. The ligands included in the study were Propolis Neoflavanoide 1, Carvacrol, Cinnamaldehyde, Thymol, p-benzoquinone, and Ciprofloxacin (standard drug S*). The outcomes of molecular docking revealed that Propolis Neoflavaniode-1 showed a highly significant binding energy of - 7.1 and - 7.2 kcal/mol for the two gram-positive bacteria, as compared to the gram-negative bacteria. All ligands demonstrated acute toxicity (oral, dermal), except for Propolis Neoflavanoide 1 and S* drugs, with a confidence score range of 50-60%. Using a molecular dynamic simulation approach, we investigated Propolis Neoflavaniode-1's potential for therapeutic use in more detail. An MD simulation lasting 100 ns was performed using the Desmond Simulation software to examine the conformational stability and steady state of Propolis Neoflavaniode-1 in protein molecule complexes. Additionally, in vitro studies confirmed the antimicrobial activity of Propolis Neoflavaniode 1 by increasing the zone of inhibition against Gram-positive bacteria, p < 0.005 as compared to gram-negative bacteria. This study revealed the promising antibacterial efficacy of Propolis Neoflavaniode 1, demonstrated through robust in silico analyses, minimal toxicity, and confirmed in vitro antimicrobial activity, suggesting its potential as a viable alternative to combat antibiotic resistance.
RESUMO
Ribosome-inactivating proteins (RIPs) are highly active N-glycosidases that depurinate both bacterial and eukaryotic rRNAs, halting protein synthesis during translation. Found in a diverse spectrum of plant species and tissues, RIPs possess antifungal, antibacterial, antiviral, and insecticidal properties linked to plant defense. In this study, we investigated the physiochemical properties of RIP peptides from the Cucurbitaceae family through bioinformatics approaches. Molecular weight, isoelectric point, aliphatic index, extinction coefficient, and secondary structures were analyzed, revealing their hydrophobic nature. The novelty of this work lies in the comprehensive examination of RIPs from the Cucurbitaceae family and their potential therapeutic applications. The study also elucidated the binding interactions of Cucurbitaceae RIPs with key biological targets, including Interleukin-6 (IL-6). Strong hydrogen bond interactions between RIPs and these targets suggest potential for innovative insilico drug design and therapeutic applications, particularly in cancer treatment. Comprehensive analysis of bond lengths using Ligpolt + software provides insights for optimizing molecular interactions, offering a valuable tool for drug design and structural biology studies.
RESUMO
Heterojunction nanocomposites (ZnO:NiO:CuO) were synthesized via a hydrothermal method and annealed at three different temperatures (400 °C, 600 °C, and 800 °C). The structural, optical, and electrical properties were examined by employing XRD, SEM, UV-Vis, FTIR, and LCR meter techniques to investigate the effects of annealing. Increasing the annealing temperature resulted in the nanocomposites (NCPs) exhibiting enhanced crystallinity, purity, optical properties, and improved electrical and dielectric behavior. The calculated crystalline sizes (Debye-Scherrer method) of the NCPs were determined to be 21, 26 and 34 nm for annealing temperature 400 °C, 600 °C, and 800 °C, respectively. The calculated bandgaps of synthesized samples were found in the range of 2.92-2.55 eV. This temperature-dependent annealing process notably influenced particle size, morphology, band-gap characteristics, and photocatalytic efficiency. EDX analysis affirmed the sample purity, with elemental peaks of Zn, Cu, Ni, and O. These NCPs demonstrated exceptional photocatalytic activity against various dyes solutions (Methyl orange (MO), Methylene Blue (MB), and mixed solution of dyes) under sunlight and also showed good antibacterial properties assessed by the disc diffusion method. Notably, the nanocomposite annealed at 400 °C exhibited a particularly high degradation efficiency by degrading 96% MB and 91% MO in just 90 min under sunlight.
RESUMO
Pleurotus florida (Mont.) Singer is a mushroom species known to be an antioxidant, immunomodulatory, and diuretic agent, reducing blood pressure and cholesterol. The aim of this study was to evaluate the in vivo potency of P. florida's anti-diabetic properties in rats affected by hyperglycemia induced by Streptozotocin (STZ) at 55 mg/kg (i.p.), characterized by oxidative stress impairment, and changes in insulin levels and lipid profile. After inducing hyperglycemia in the rats, they were treated with P. florida acetone and methanol extracts, orally administered for 28 days at doses of 200 mg/kg and 400 mg/kg body weight. The hyperglycemic control (DC) group showed significant increases (P < 0.05) in mean blood sugar, total cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, blood urea nitrogen, lipid hydroperoxides, and malondialdehyde, compared to the normal control (NC) group The high-density lipoprotein cholesterol, serum insulin, superoxide dismutase, catalase, glutathione disulfide, glutathione peroxidase, reduced glutathione, guaiacol peroxidase, and vitamin E and C levels showed a significant decrease (P < 0.05) in DC group, compared to the NC group. Blood glucose levels, lipid profiles, and insulin levels improved significantly after 28 days of treatment, in the group treated with glibenclamide (an oral hypoglycemic drug, used as positive control), and in the groups treated with P. florida extracts. In DC group, the treatment with P. florida was found to prevent diabetes, according to histopathological studies of the kidneys, pancreas, and liver of rats. In conclusion, this study has shown that the treatment with P. florida decreased oxidative stress and glucose levels in the blood, as well as restoring changes in lipid profiles.
Assuntos
Hiperglicemia , Insulinas , Pleurotus , Ratos , Animais , Estreptozocina , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Antioxidantes/metabolismo , Estresse Oxidativo , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Peróxidos Lipídicos , Glicemia , Colesterol , Lipoproteínas LDLRESUMO
Cystic Fibrosis Transmembrane Regulator (CFTR) is a significant protein that is responsible for the movement of ions across cell membranes. The cystic fibrosis (CF) occur due to the mutations in the CFTR gene as it produces the dysfunctional CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands selection was performed through virtual screening and top 3 ligands choose out of 65 ligands silibinins, curcumin, demethoxycurcumin were selected with a reference drug Trikafta (R*). According to docking, ADMET analyses, the natural ligands (Silibinins and Curcumin) displayed best binding energy, pharmacokinetic and free toxicity than other natural compounds and reference drug (R*). An MD simulation for 200 ns was also established to ensure that natural ligands (Silibinins and Curcumin) attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that silibinins and curcumins have a better capacity to decrease the effect of mutant CFTR protein through improved trafficking and the restoration of original function. In conclusion, in silico studies demonstrate the potential of silibinins and curcumin as therapeutic agents for cystic fibrosis, particularly for the D614G mutated protein. Their ability to increase CFTR function while reducing cellular stress and inflammation, together with their favorable safety profile and accessibility could make them valuable additions to cystic fibrosis treatment options. Further experimental and clinical validation will be required to fully realize their potential and include them into effective therapy regimens.