RESUMEN
Fluoride induced reprotoxicity through oxidative stress-mediated reproductive cell death. Hence, the current study evaluated the importance of the MST/Nrf2/MAPK/NQO-HO1 signaling pathway in fluorosis-induced reproductive toxicity. For this purpose, the reproductive toxicity of sodium fluoride (NaF) at physiological, biochemical, and intracellular levels was evaluated. In-vivo, NaF at 100 mg/L instigated physiological dysfunction, morphological, stereological, and structural injuries in the gut-gonadal axis of fluorosis mice through weakening the antioxidant signaling, Nrf2/HO-1/NQO1signaling pathway, causing the gut-gonadal barrier disintegrated via oxidative stress-induced inflammation, mitochondrial damage, apoptosis, and autophagy. Similar trends were also observed in-vitro in the isolated Leydig cells (LCs) challenging with 20 mg/L NaF. Henceforth, activating the cellular antioxidant signaling pathway, Nrf2/HO-1/NQO1, inactivating autophagy and apoptosis, or attenuating lipopolysaccharide (LPS) can be the theoretical basis and valuable therapeutic targets for coping with NaF-induced reproductive toxicity.
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Antioxidantes , Factor 2 Relacionado con NF-E2 , Masculino , Ratones , Animales , Antioxidantes/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Transducción de Señal , Estrés Oxidativo , Fluoruro de Sodio/toxicidad , ApoptosisRESUMEN
Verbascum thapsus (VT) is a medicinal plant that is used in folk medicine to treat a variety of ailments. For this study, the biological functions of VT methanol extract were determined in vitro. The plant's methanol extract was created through the maceration process. The phytochemical composition of plant extracts was investigated using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The antioxidant capacity of the extract was determined using the DPPH (2,2-diphenyl-1-picrylhydrazil) and ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) tests and its cytotoxicity was assessed using the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole)) assay on the Caco-2 (human colorectal adenocarcinoma cells), LNCaP (Lymph Node Carcinoma of the Prostate), and HEK293 cell lines (Human embryonic kidney 293 cells) used to model colon, prostate, and non-cancerous cells. VT extract showed low DPPH and ABTS radical scavenging activities compared to standard antioxidants at 30 mg/ml concentration. In addition, it was determined that VT extract inhibited acetylcholinesterase enzyme.
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Antioxidantes , Benzotiazoles , Ácidos Sulfónicos , Verbascum , Masculino , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Espectrometría de Masas en Tándem , Células CACO-2 , Acetilcolinesterasa , Metanol/química , Células HEK293 , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fitoquímicos/análisisRESUMEN
A study of grape snails (Helix pomatia) using the electron paramagnetic resonance (EPR) spectroscopy method, where shells were exposed to ionizing gamma radiation, indicated that the effect of radiation up to certain doses results in the emergence of magnetic properties in the organism. The identification of the EPR spectra of the body and shell parts of the control and irradiated grape snails separately showed that more iron oxide magnetic nanoparticles are generated in the body part of the grape snail compared to the shells. A linear increase in free radical signals (g = 2.0023) in the body and shell parts of grape snails, and a non-monotonic change in the broad EPR signal (g = 2.32) characterizing iron oxide magnetic nanoparticles was determined depending on the dose of ionizing gamma radiation. Additionally, the obtained results showed that grape snails can be used as bioindicators for examining the ecological state of the environment. At the same time, the radionuclide composition of the body and shell parts of the grape snails and their specific activities were determined by CANBERRA gamma spectroscopy. The FTIR spectra of mucin, a liquid secreted by snails, were recorded.
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Vitis , Animales , Espectroscopía de Resonancia por Spin del Electrón , Caracoles , Caracoles HelixRESUMEN
The present work deals with the green synthesis and characterization of silver nanoparticles (AgNPs) using Allium cepa (yellowish peel) and the evaluation of its antimicrobial, antioxidant, and anticholinesterase activities. For the synthesis of AgNPs, peel aqueous extract (200 mL) was treated with a 40 mM AgNO3 solution (200 mL) at room temperature, and a color change was observed. In UV-Visible spectroscopy, an absorption peak formation at ~439 nm was the sign that AgNPs were present in the reaction solution. UV-vis, FE-SEM, TEM, EDX, AFM, XRD, TG/DT analyses, and Zetasizer techniques were used to characterize the biosynthesized nanoparticles. The crystal average size and zeta potential of AC-AgNPs with predominantly spherical shapes were measured as 19.47 ± 1.12 nm and -13.1 mV, respectively. Pathogenic microorganisms Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were used for the Minimum Inhibition Concentration (MIC) test. When compared to tested standard antibiotics, AC-AgNPs demonstrated good growth inhibitory activities on P. aeuruginosa, B. subtilis, and S. aureus strains. In vitro, the antioxidant properties of AC-AgNPs were measured using different spectrophotometric techniques. In the ß-Carotene linoleic acid lipid peroxidation assay, AC-AgNPs showed the strongest antioxidant activity with an IC50 value of 116.9 µg/mL, followed by metal-chelating capacity and ABTS cation radical scavenging activity with IC50 values of 120.4 µg/mL and 128.5 µg/mL, respectively. The inhibitory effects of produced AgNPs on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were determined using spectrophotometric techniques. This study provides an eco-friendly, inexpensive, and easy method for the synthesis of AgNPs that can be used for biomedical activities and also has other possible industrial applications.
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Antioxidantes , Nanopartículas del Metal , Antioxidantes/química , Staphylococcus aureus , Inhibidores de la Colinesterasa/farmacología , Plata/química , Cebollas , Nanopartículas del Metal/química , Butirilcolinesterasa/farmacología , Acetilcolinesterasa/farmacología , Antibacterianos/farmacología , Extractos Vegetales/químicaRESUMEN
The current work's main objective was to determine the chemical composition of Amygdalus communis (AC) leaf extract and examine the antibacterial and cytotoxic properties of biosynthesized gold nanoparticles (AuNPs). The chemical composition of AC leaf extract was determined using LC-ESI/MS/MS to detect compounds that may be responsible for the reducing, stabilizing, and capping steps in the synthesis of nanoparticles and their biological activities. The AC-AuNPs were spherical, with a particle size lower than 100 nm and a face-centered cubic structure. The EDX spectrum confirmed the formation of AuNPs and a negative zeta potential value (-27.7 mV) suggested their physicochemical stability. The in vitro cytotoxic efficacy of the AC-AuNPs against colorectal adenocarcinoma (Caco-2), glioma (U118), and ovarian (Skov-3) cancer cell lines and human dermal fibroblasts (HDFs) was evaluated by MTT assay. CaCo-2 cell proliferation was effectively inhibited by the AC-AuNPs at concentrations between 25 and 100 g mL-1. The AC-AuNPs exerted preeminent antimicrobial activity against Bacillus subtilis with an MIC of 0.02 µg/mL, whilst good activity was shown against Staphylococcus aureus bacteria and Candida albicans yeast with an MIC of 0.12 µg/mL. Ultimately, the results support the high antibacterial and anticancer potential of biosynthesized AuNPs from AC leaf extract.
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Antiinfecciosos , Antineoplásicos , Nanopartículas del Metal , Prunus dulcis , Humanos , Oro/farmacología , Oro/química , Células CACO-2 , Espectrometría de Masas en Tándem , Nanopartículas del Metal/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antibacterianos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Tecnología Química VerdeRESUMEN
Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 µM in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 µM IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Humanos , Inhibidores de la Dipeptidil-Peptidasa IV/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Simulación del Acoplamiento Molecular , Sulfonamidas/farmacología , Sulfonamidas/química , Dipeptidil Peptidasa 4/química , Pruebas de EnzimasRESUMEN
In recent years, stem cells have known as a helpful biological tool for the accurate diagnosis, treatment and recognition of diseases. Using stem cells as biomarkers have presented high potential in the early detection of many diseases. Another advancement in stem cell technology includes stem cell derived organoids model that could be a promising platform for diagnosis and modeling different diseases. Furthermore, therapeutic capabilities of stem cell therapy have increased hope in the face of different disability managements. All of these technologies are also widely used in reproductive related diseases especially in today's world that many couples encounter infertility problems. However, with the aid of numerous improvements in the treatment of infertility, over 80% of couples who dreamed of having children could now have children. Due to the fact that infertility has many negative effects on personal and social lives of young couples, many researchers have focused on the treatment of male and female reproductive system abnormalities with different types of stem cells, including embryonic stem cells, bone marrow mesenchymal stem cells (MSCs), and umbilical cord-derived MSCs. Also, design and formation of reproductive system organoids provide a fascinating window into disease modeling, drug screening, personalized therapy, and regeneration medicine. Utilizing these techniques to study, model and treat the infertility-related diseases has drawn attention of many scientists. This review explains different applications of stem cells in generating reproductive system organoids and stem cell-based therapies for male and female infertility related diseases treatment.
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Infertilidad Femenina , Organoides , Niño , Células Madre Embrionarias , Femenino , Genitales , Humanos , Infertilidad Femenina/terapia , Masculino , TecnologíaRESUMEN
Laccase producing fungus Pleurotus floridanus was isolated from Siruvani forest, Tamil Nadu, India. The potential of P. floridanus to produce laccase by using various lignocellulosic substrates was screened under submerged fermentation. Laccase production in the presence of lignocellulosic substrates such as rice, wheat and maize bran as a sole source of carbon as well as an additional supplement was examined. Laccase activity of P. floridanus using varied substrates was observed in the order of rice bran > wheat bran > maize bran. The isolate showed maximum laccase activity of 13.29±0.01 U/mL using rice bran as a carbon source within 11 days. This was 18 fold higher than the control media that lacks lignocellulosic substrates. The diclofenac tolerance was assessed in solid media at various concentrations and the results showed that the mycelia growth is not significantly affected by the drug. Finally, the laccase mediated degradation of diclofenac at a concentration of 10 mg/L showed 98% degradation in 2 h. The phytotoxicity of the crude laccase treated diclofenac was lower than the untreated diclofenac. In conclusion, findings suggested direct application of crude laccase produced from P. floridanus using agro-residues as ideal substrate for environmental applications.
Asunto(s)
Lacasa , Pleurotus , Biotransformación , Carbono , Diclofenaco/toxicidad , India , Lacasa/metabolismo , Pleurotus/metabolismoRESUMEN
Curcumin is a phytochemical achieved from the plant turmeric. It is extensively utilized for the treatment of several types of diseases such as cancers. Nevertheless, its efficiency has been limited because of rapid metabolism, low bioavailability, poor water solubility, and systemic elimination. Scientists have tried to solve these problems by exploring novel drug delivery systems such as lipid-based nanoparticles (NPs) (e.g., solid lipid NPs, nanostructured lipid carriers, and liposomes), polymeric NPs, micelles, nanogels, cyclodextrin, gold, and mesoporous silica NPs. Among these, liposomes have been the most expansively studied. This review mainly focuses on the different curcumin nanoformulations and their use in cancer therapy in vitro, in vivo, and clinical studies. Despite the development of curcumin-containing NPs for the treatment of cancer, potentially serious side effects, including interactions with other drugs, some toxicity aspects of NPs may occur that require more high-quality investigations to firmly establish the clinical efficacy.
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Curcumina , Nanopartículas , Neoplasias , Curcumina/farmacología , Curcumina/uso terapéutico , Portadores de Fármacos/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Micelas , Nanomedicina , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológicoRESUMEN
Brain disorders such as Alzheimer's and Parkinson's disease (PD) are irreversible conditions with several cognitive problems, including learning disabilities, memory loss, movement abnormalities, and speech problems. These disorders are caused by a variety of factors, mainly due to the toxic pollutants-induced biochemical changes in protein production, uncontrolled neuronal electrical activity, and altered neurotransmitter levels. Oxidative stress and toxicity associated with the increased glutamate levels decreased acetylcholine levels, and brain inflammation is the main contributing factor. Melatonin hormone is considered one of the potent treatment approaches for neurodegenerative disorders. Melatonin is released from the pineal gland and has a critical role in brain function regulation. Membrane receptors, binding sites, and chemical interaction mediate hormonal actions having multiple phenotypic expressions. It acts as a neurodegenerative agent against some neurological disorders such as Alzheimer's disease (AD), PD, depression, and migraines. Melatonin inhibits neurotoxic pollutants-induced Tau protein hyperphosphorylation, especially in AD. Other pivotal features of melatonin are its anti-inflammatory properties, which decrease pro-inflammatory cytokines expression and factors such as IL-8, IL-6, and TNF. Melatonin also reduces NO (an inflammation factor). In this review, we have highlighted the protective effects of melatonin, mainly spotlighting its neuroprotective mechanisms that will be beneficial to assess their effects in environmental pollution-induced neurodegenerative pathology.
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Enfermedad de Alzheimer/prevención & control , Melatonina/uso terapéutico , Enfermedades Neurodegenerativas/prevención & control , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/prevención & control , Enfermedad de Alzheimer/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Humanos , Melatonina/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/metabolismo , Fosforilación/efectos de los fármacos , Glándula Pineal/metabolismo , Proteínas tau/metabolismoRESUMEN
Cartilage is frequently damaged with a limited capacity for repair. Current treatment strategies are insufficient as they form fibrocartilage as opposed to hyaline cartilage, and do not prevent the progression of degenerative changes. There is increasing interest in the use of autologous mesenchymal stem cells (MSC) for tissue regeneration. MSCs that are used to treat articular cartilage defects must not only present a robust cartilaginous production capacity, but they also must not cause morbidity at the harvest site. In addition, they should be easy to isolate from the tissue and expand in culture without terminal differentiation. The source of MSCs is one of the most important factors that may affect treatment. The infrapatellar fat pad (IPFP) acts as an important reservoir for MSC and is located in the anterior compartment of the knee joint in the extra-synovial area. The IPFP is a rich source of MSCs, and in this review, we discuss studies that demonstrate that these cells have shown many advantages over other tissues in terms of ease of isolation, expansion, and chondrogenic differentiation. Future studies in articular cartilage repair strategies and suitable extraction as well as cell culture methods will extend the therapeutical application of IPFP-derived MSCs into additional orthopedic fields, such as osteoarthritis. This review provides the latest research concerning the use of IPFP-derived MSCs in the treatment of articular cartilage damage, providing critical information for the field to grow.
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Tejido Adiposo/citología , Regeneración Ósea , Cartílago Articular/citología , Cartílago Articular/fisiología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Animales , Técnicas de Cultivo de Célula , Tratamiento Basado en Trasplante de Células y Tejidos , Humanos , Osteogénesis , Cicatrización de HeridasRESUMEN
Paraquat (PQ) as a herbicide and an environmental pollutant with increasing importance due to its toxicity to humans and animals. This study aimed to evaluate the protective and antioxidant activity of quercetin loaded Nanostructured Lipid Carriers (QNLC) against toxicity induced by PQ. Blood lymphocytes were prepared using Ficoll polysaccharide and subsequently by gradient centrifugation. The QNLC was prepared using an ultra-sonication method, which was characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The viability, reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosome membrane integrity, Bax and Bcl2 gene expression were evaluated in human isolated lymphocytes. The results showed spherical QNLCs with nano-size range (52.7 nm) and high drug encapsulation efficiency (98.5% -96%). The results also indicated that PQ induced cell death, as well as ROS production, decreased by QNLC in human lymphocytes. Also, QNLC meaningfully restored MMP reduction, lysosomal membrane destabilization, and lipid peroxidation and were capable of preventing PQ-treated change in Bax and Bcl2 gene expression. We report that QNLC, have a significantly higher capacity to prevent PQ-induced toxicity than Q itself. It is suggested that the QNLC is a promising antioxidant for drug delivery to be used as a therapeutic and prophylactic agent for PQ poisoning.
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Herbicidas , Quercetina , Animales , Humanos , Peroxidación de Lípido , Lípidos , Linfocitos , ParaquatRESUMEN
The repair and regeneration of articular cartilage represent important challenges for orthopedic investigators and surgeons worldwide due to its avascular, aneural structure, cellular arrangement, and dense extracellular structure. Although abundant efforts have been paid to provide tissue-engineered grafts, the use of therapeutically cell-based options for repairing cartilage remains unsolved in the clinic. Merging a clinical perspective with recent progress in nanotechnology can be helpful for developing efficient cartilage replacements. Nanomaterials, < 100 nm structural elements, can control different properties of materials by collecting them at nanometric sizes. The integration of nanomaterials holds promise in developing scaffolds that better simulate the extracellular matrix (ECM) environment of cartilage to enhance the interaction of scaffold with the cells and improve the functionality of the engineered-tissue construct. This technology not only can be used for the healing of focal defects but can also be used for extensive osteoarthritic degenerative alterations in the joint. In this review paper, we will emphasize the recent investigations of articular cartilage repair/regeneration via biomaterials. Also, the application of novel technologies and materials is discussed.
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Cartílago Articular , Condrogénesis , Nanoestructuras , Regeneración , Ingeniería de Tejidos , Animales , Humanos , Medicina Regenerativa , Andamios del TejidoRESUMEN
OBJECTIVES: A wide range of compounds are utilized in dentistry such as dental composites, resins, and implants. The successful clinical use of dental materials relies on theirm physiochemical properties as well as biological and toxicological reliability. Different local and systemic toxicities of dental materials have been reported. Placement of these materials in oral cavity for a long time period might yield unwanted reactions. An extensive variety of materials is used in dentistry including filling materials, restorative materials, intracanal medicines, prosthetic materials, different types of implants, liners, and irrigants. The increasing rate in development of the novel materials with applications in the dental field has led to an increased consciousness of the biological risks and tempting restrictions of these materials. The biocompatibility of a biomaterial used for the replacement or filling of biological tissue such as teeth always had a high concern within the health care disciplines for patients. MATERIALS AND METHODS: Any material used in humans should be tested before clinical application. There are many tests evaluating biocompatibility of these materials at the point of in vitro, in vivo, and clinical investigations. RESULTS: The current review discusses the potential toxicity of dental material and screening of their biocompatibility. CLINICAL RELEVANCE: It is essential to use healthy and safe materials medical approaches. In dentistry, application of different materials in long-term oral usage demands low or nontoxic agents gains importance for both patients and the staff. Furthermore, screening tests should evaluate any potential toxicity before clinical application.
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Materiales Biocompatibles/toxicidad , Materiales Dentales/toxicidad , Humanos , Ensayo de MaterialesRESUMEN
Organophosphates (OP) are potent pesticide commonly utilized in agricultural and domestic use. However, plentitude of data represent their side effects in different body tissues. We attempted to study whether betanin (a natural pigment) is able to mitigate some OPs-induced hepatotoxicity in primary rat hepatocytes. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), glutathione (GSH) depletion and mitochondrial depolarization were tested as toxicity markers. The outcomes revealed that betanin (25µM) significantly increased cell viability, plummeted ROS formation and LPO, restored cellular GSH reservoirs and protected mitochondria after chlorpyrifos (CPF) (300µM), diazinon (DZN) (600µM) and dichlrovos (DDVP) (400µM) treatment. Taken together, all data suggests the potential protective role of betanin in OPs-induced hepatotoxicity in which the mechanism appears to be inhibition of ROS formation and mitochondrial protection.
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Antioxidantes/farmacología , Betacianinas/farmacología , Supervivencia Celular/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Organofosfatos/toxicidad , Plaguicidas/toxicidad , Animales , Células Cultivadas , Cloropirifos/toxicidad , Diazinón/toxicidad , Diclorvos/toxicidad , Glutatión/metabolismo , Hepatocitos/enzimología , Hepatocitos/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Peroxidación de Lípido , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias Hepáticas/enzimología , Mitocondrias Hepáticas/metabolismo , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Development of biocompatible antioxidant nanoparticles for xenobiotic-induced liver disease treatment by oral or parenteral administration is of great interest in medicine. In the current study, we demonstrate the protective effects of coenzyme Q10 nanoparticles (CoQ10-NPs) on hepatotoxicity induced by dichlorvos (DDVP) as an organophosphate. Although CoQ10 is an efficient antioxidant, its poor bioavailability has limited the applications of this useful agent. First, CoQ10-NPs were prepared then characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In DDVP-treated and non-treated hepatocytes in the presence of CoQ10-NPs, cell viability, the level of reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosome membrane integrity, and cellular glutathione (GSH) content were measured. The prepared CoQ10-NPs were mono-dispersed and had narrow size distribution with average diameter of 54 nm. In the in vivo study, we evaluated the enzymes, which are involved in the antioxidant system for maintenance of normal liver function. In comparison to nonparticulate CoQ10, the CoQ10-NPs efficiently decreased the ROS formation, lipid peroxidation and cell death. Also, particulate form of CoQ10 improved MMP, GSH level and lysosome membrane integrity. In the in vivo, study, we revealed that CoQ10-NPs were better hepatoprotective than its nonparticulate form (P < .05). Altogether, we propose that the CoQ10-NPs have potential capability to be used as a therapeutic and prophylactic agent for poisoning that is induced by organophosphate agents, especially in the case of DDVP. Furthermore, these positive remarks make this nanoparticle amenable for the treatment of xenobiotic-induced liver diseases.
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Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Lisosomas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Nanopartículas/química , Sustancias Protectoras/farmacología , Ubiquinona/análogos & derivados , Animales , Antioxidantes/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Diclorvos/toxicidad , Glutatión/metabolismo , Hepatocitos/citología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Lisosomas/metabolismo , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Sustancias Protectoras/química , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Ubiquinona/química , Ubiquinona/farmacologíaRESUMEN
1. Olanzapine (OLZ) is a widely used atypical antipsychotic agent for the treatment of schizophrenia and other disorders. Serious hepatotoxicity and elevated liver enzymes have been reported in patients receiving OLZ. However, the cellular and molecular mechanisms of the OLZ hepatotoxicity are unknown. 2. In this study, the cytotoxic effect of OLZ on freshly isolated rat hepatocytes was assessed. Our results showed that the cytotoxicity of OLZ in hepatocytes is mediated by overproduction of reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation preceding cell lysis. All the aforementioned OLZ-induced cellular events were significantly (p < 0.05) prevented by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate generators. Also, the present results demonstrated that CYP450 is involved in OLZ-induced oxidative stress and cytotoxicity mechanism. 3. It is concluded that OLZ hepatotoxicity is associated with both mitochondrial/lysosomal involvement following the initiation of oxidative stress in hepatocytes.
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Benzodiazepinas/farmacología , Hepatocitos/metabolismo , Hepatocitos/patología , Lisosomas/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Animales , Antioxidantes/metabolismo , Muerte Celular/efectos de los fármacos , Separación Celular , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Disulfuro de Glutatión/metabolismo , Hepatocitos/efectos de los fármacos , Membranas Intracelulares/efectos de los fármacos , Membranas Intracelulares/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Lisosomas/efectos de los fármacos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Olanzapina , Fenobarbital , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The hepatotoxic effects of the antipsychotic agent, risperidone (RIS) were investigated for better understanding the pathogenesis of RIS in liver toxicity in vivo and in in vitro. Isolated rat hepatocytes were obtained by collagenase perfusion technique and were then incubated with RIS, different antioxidants in particular coenzyme Q10 (CoQ10), N-acetyl cysteine (NAC). Our results showed that RIS could induce cytotoxicity via rising reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation. All of these effects were significantly (p < 0.05) inhibited by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate (ATP) generators. Similar outcomes were obtained from the in vivo experiments. Liver function enzyme test and histopathological evaluation confirmed RIS-(6 mg/kg) induced damage. Based on these results, it is suggested that RIS-induced liver toxicity is associated with mitochondrial/lysosomal cross-talk following the initiation of oxidative stress. Thus, the use of CoQ10 and/or NAC seems to be a safe therapeutic option in this context.
Asunto(s)
Acetilcisteína/farmacología , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Estrés Oxidativo/efectos de los fármacos , Risperidona/toxicidad , Ubiquinona/análogos & derivados , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Ubiquinona/farmacologíaRESUMEN
In recent years, the intensive production of nanoparticles with a wide application has led to their transfer to the environment, including the water ecosystem. The accumulation of nanoparticles in fish, causing various pathological changes in the host, raises certain concerns. In the current study, we investigated the penetration and bioaccumulation of Fe3O4 nanoparticles, in the liver of common carp (Cyprinus carpio Linnaeus, 1758). Common carp juveniles were exposed to Fe3O4 nanoparticles at concentrations of 10 and 100 mg. After 7 days, their livers were examined by light and transmission electron microscopes. Compared to normal fish's liver, after using a small concentration (10 mg) of nanoparticles, changes were observed in erythrocytes, hepatocytes, intracellular canaliculi, and bile ducts of the liver. At a high concentration (100 mg), the intensity of changes increased significantly. The liver's capsule was damaged, and a considerable number of hepatocytes were completely destroyed. Additionally, the walls of blood vessels and biliary ductule walls was notably disturbed. It was found that the intensity of pathologies occurring in the liver, increases proportionally with higher concentrations of nanoparticles. Confirmation via electron microscopic methods revealed that Fe3O4 nanoparticles, when administered with food to common carp, enter the fish's liver through erythrocytes localized in the lumen of blood vessels. From there, they traverse through the endothelium of vessels, proceed to hepatocytes, including cytoplasmic organelles, intracellular canaliculi, biliary ductules, and eventually reach the bile ducts. Fe3O4 nanoparticles in all structural elements of fish liver was up to 20 nm. Therefore, high concentrations of nanoparticles in the environment harms the bodies of aquatic organisms, including fish. The changes identified in the liver of common carp in the present study are valuable information in assessing possible risks to other components of the aquatic ecosystem and organisms.
Asunto(s)
Carpas , Hígado , Contaminantes Químicos del Agua , Animales , Carpas/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/ultraestructura , Contaminantes Químicos del Agua/toxicidad , Microscopía Electrónica de Transmisión , Nanopartículas Magnéticas de Óxido de Hierro/toxicidadRESUMEN
Alzheimer's disease is a neurological disorder that causes increased memory loss, mood swings, behavioral disorders, and disruptions in daily activities. Polymer scaffolds for the brain have been grown under laboratory, physiological, and pathological circumstances because of the limitations of conventional treatments for patients with central nervous system diseases. The blood-brain barrier prevents medications from entering the brain, challenging AD treatment. Numerous biomaterials such as biomolecules, polymers, inorganic metals, and metal oxide nanoparticles have been used to transport therapeutic medicines into the nervous system. Incorporating biocompatible materials that support neurogenesis through a combination of topographical, pharmacological, and mechanical stimuli has also shown promise for the transfer of cells to replenish dopaminergic neurons. Components made of naturally occurring biodegradable polymers are appropriate for the regeneration of nerve tissue. The ability of natural-based materials (biomaterials) has been shown to promote endogenous cell development after implantation. Also, strategic functionalization of polymeric nanocarriers could be employed for treating AD. In particular, nanoparticles could resolve Aß aggregation and thus help cure Alzheimer's disease. Drug moieties can be effectively directed to the brain by utilizing nano-based systems and diverse colloidal carriers, including hydrogels and biodegradable scaffolds. Notably, early investigations employing neural stem cells have yielded promising results, further emphasizing the potential advancements in this field. Few studies have fully leveraged the combination of cells with cutting-edge biomaterials. This study provides a comprehensive overview of prior research, highlighting the pivotal role of biomaterials as sophisticated drug carriers. It delves into various intelligent drug delivery systems, encompassing pH and thermo-triggered mechanisms, polymeric and lipid carriers, inorganic nanoparticles, and other vectors. The discussion synthesizes existing knowledge and underscores the transformative impact of these biomaterials in devising innovative strategies, augmenting current therapeutic methodologies, and shaping new paradigms in the realm of Alzheimer's disease treatment.