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This study synthesized zinc oxide nanoparticles (ZnO NPs) using a novel green approach, with Sida acuta leaf extract as a capping and reducing agent to initiate nucleation and structure formation. The innovation of this study lies in demonstrating the originality of utilizing zinc oxide nanoparticles for antibacterial action, antioxidant potential, and catalytic degradation of Congo red dye. This unique approach harnesses eco-friendly methods to initiate nucleation and structure formation. The synthesized nanoparticles' structure and conformation were characterized using UV-vis (λmax = 280 nm), X-ray, atomic force microscopy, SEM, HR-TEM and FTIR. The antibacterial activity of the Nps was tested against Pseudomonas sp, Klebsiella sp, Staphylococcus aureus, and E. coli, demonstrating efficacy. The nanoparticles exhibited unique properties, with a crystallite size of 20 nm (XRD), a surface roughness of 2.5 nm (AFM), and a specific surface area of 60 m2/g (SEM). A Convolutional Neural Network (CNN) was effectively employed to accurately classify and analyze microscopic images of green-synthesized zinc oxide nanoparticles. This research revealed their exceptional antioxidant potential, with an average DPPH scavenging rate of 80% at a concentration of 0.05 mg/mL. Additionally, zeta potential measurements indicated a stable net negative surface charge of approximately -12.2 mV. These quantitative findings highlight the promising applications of green-synthesized ZnO NPs in healthcare, materials science, and environmental remediation. The ZnO nanoparticles exhibited catalytic capabilities for dye degradation, and the degradation rate was determined using UV spectroscopy. Key findings of the study encompass the green synthesis of versatile zinc oxide nanoparticles, demonstrating potent antibacterial action, antioxidant capabilities, and catalytic dye degradation potential. These nanoparticles offer multifaceted solutions with minimal environmental impact, addressing challenges in various fields, from healthcare to environmental remediation.
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Antibacterianos , Antioxidantes , Tecnología Química Verde , Extractos Vegetales , Hojas de la Planta , Óxido de Zinc , Óxido de Zinc/química , Óxido de Zinc/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Hojas de la Planta/química , Tecnología Química Verde/métodos , Nanopartículas del Metal/química , Redes Neurales de la Computación , Catálisis , Rojo Congo/química , Colorantes/químicaRESUMEN
Rice serves as a staple food across various continents worldwide. The rice plant faces significant threats from a range of fungal, bacterial, and viral pathogens. Among these, rice false smut disease (RFS) caused by Villosiclava virens is one of the devastating diseases in rice fields. This disease is widespread in major rice-growing regions such as China, Pakistan, Bangladesh, India, and others, leading to significant losses in rice plantations. Various toxins are produced during the infection of this disease in rice plants, impacting the fertilization process as well. This review paper lightens the disease cycle, plant immunity, and infection process during RFS. Mycotoxin production in RFS affects rice plants in multiple ways, although the exact phenomena are still unknown.
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Scientists are focusing immense attention on polymeric nanocarriers as a prominent delivery vehicle for several biomedical applications including diagnosis of diseases, delivery of therapeutic agents, peptides, proteins, genes, siRNA, and vaccines due to their exciting physicochemical characteristics which circumvent degradation of unstable drugs, reduce toxic side effects through controlled release, and improve bioavailability. Polymers-based nanocarriers offer numerous benefits for in vivo drug delivery such as biocompatibility, biodegradability, non-immunogenicity, active drug targeting via surface modification, and controlled release due to their pH-and thermosensitive characteristics. Despite their potential for medicinal use, regulatory approval has been achieved for just a few. In this review, we discuss the historical development of polymers starting from their initial design to their evolution as nanocarriers for therapeutic delivery of drugs, peptides, and genes. The review article also expresses the applications of polymeric nanocarriers in the pharmaceutical and medical industry with a special emphasis on oral, ocular, parenteral, and topical application of drugs, peptides, and genes over the last two decades. The review further examines the practical, regulatory, and clinical considerations of the polymeric nanocarriers, their safety issues, and directinos for future research.
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Over the past few decades, gene therapy has gained immense importance in medical research as a promising treatment strategy for diseases such as cancer, AIDS, Alzheimer's disease, and many genetic disorders. When a gene needs to be delivered to a target cell inside the human body, it has to pass a large number of barriers through the extracellular and intracellular environment. This is why the delivery of naked genes and nucleic acids is highly unfavorable, and gene delivery requires suitable vectors that can carry the gene cargo to the target site and protect it from biological degradation. To date, medical research has come up with two types of gene delivery vectors, which are viral and nonviral vectors. The ability of viruses to protect transgenes from biological degradation and their capability to efficiently cross cellular barriers have allowed gene therapy research to develop new approaches utilizing viruses and their different genomes as vectors for gene delivery. Although viral vectors are very efficient, science has also come up with numerous nonviral systems based on cationic lipids, cationic polymers, and inorganic particles that provide sustainable gene expression without triggering unwanted inflammatory and immune reactions, and that are considered nontoxic. In this review, we discuss in detail the latest data available on all viral and nonviral vectors used in gene delivery. The mechanisms of viral and nonviral vector-based gene delivery are presented, and the advantages and disadvantages of all types of vectors are also given.
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Terapia Genética , Ácidos Nucleicos , Cationes , Técnicas de Transferencia de Gen , Vectores Genéticos/genética , HumanosRESUMEN
Highly active anti-retroviral therapy (HAART) is prescribed for HIV infection and, to a certain extent, limits the infection's spread. However, it cannot completely eradicate the latent virus in remote and cellular reservoir areas, and due to the complex nature of the infection, the total eradication of HIV is difficult to achieve. Furthermore, monotherapy and multiple therapies are not of much help. Hence, there is a dire need for novel drug delivery strategies that may improve efficacy, decrease side effects, reduce dosing frequency, and improve patient adherence to therapy. Such a novel strategy could help to target the reservoir sites and eradicate HIV from different biological sanctuaries. In the current review, we have described HIV pathogenesis, the mechanism of HIV replication, and different biological reservoir sites to better understand the underlying mechanisms of HIV spread. Further, the review deliberates on the challenges faced by the current conventional drug delivery systems and introduces some novel drug delivery strategies that have been explored to overcome conventional drug delivery limitations. In addition, the review also summarizes several nanotechnology-based approaches that are being explored to resolve the challenges of HIV treatment by the virtue of delivering a variety of anti-HIV agents, either as combination therapies or by actively targeting HIV reservoir sites.
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A high incidence of dementia (60-80%) and a high rate of memory loss are two of the most common symptoms of Alzheimer's disease (AD), which affects the elderly. Researchers have recommended that traditional Chinese medicine (TCM) and Indian medicines can be used to prevent and cure AD. Several studies have linked neuroinflammation linked to amyloid-ß (Aß) deposition in the brain to the pathophysiology of neurodegenerative disorders. As a result, more research is needed to determine the role of inflammation in neurodegeneration. Increased microglial activation, cytokine production, reactive oxygen species (ROS), and nuclear factor kappa B (NF-κB) all play a role in the inflammatory process of AD. This review focuses on the role of neuroinflammation in neuroprotection and the molecular processes used by diverse natural substances, phytochemicals, and herbal formulations in distinct signaling pathways. Currently, researchers are focusing on pharmacologically active natural compounds with the anti-neuroinflammatory potential, making them a possible contender for treating AD. Furthermore, the researchers investigated the limits of past studies on TCM, Indian Ayurveda, and AD. Numerous studies have been carried out to examine the effects of medicinal whole-plant extracts on AD. Clinical investigations have shown that lignans, flavonoids, tannins, polyphenols, triterpenoids, sterols, and alkaloids have anti-inflammatory, antiamyloidogenic, anticholinesterase, and antioxidant properties. This review summarizes information about numerous medicinal plants and isolated compounds used in the treatment of AD and a list of further references.
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Enfermedad de Alzheimer , Productos Biológicos , Plantas Medicinales , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Humanos , Fitoquímicos/uso terapéutico , Plantas Medicinales/metabolismo , Polifenoles/farmacologíaRESUMEN
One of the most significant challenges of diabetes health care is diabetic foot ulcers (DFU). DFUs are more challenging to cure, and this is particularly true for people who already have a compromised immune system. Pathogenic bacteria and fungi are becoming more resistant to antibiotics, so they may be unable to fight microbial infections at the wound site with the antibiotics we have now. This article discusses the dressings, topical antibacterial treatment, medications and debridement techniques used for DFU and provides a deep discussion of DFU and its associated problems. English-language publications on DFU were gathered from many different databases, such as Scopus, Web of Science, Science Direct, Springer Nature, and Google Scholar. For the treatment of DFU, a multidisciplinary approach involving the use of diagnostic equipment, skills, and experience is required. Preventing amputations starts with patient education and the implementation of new categorization systems. The microbiota involved in DFU can be better understood using novel diagnostic techniques, such as the 16S-ribosomal DNA sequence in bacteria. This could be achieved by using new biological and molecular treatments that have been shown to help prevent infections, to control local inflammation, and to improve the healing process.
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The present investigations were designed to describe the ultrastructural properties of the eye of the golden gray mullet (Chelon aurata). For this purpose, the eyes were examined grossly, and by light and electron microscope. The external layer consists of the cornea and the sclera. Three layers compose the cornea; the anterior stratified cuboidal epithelial; the anterior limiting (Bowman) membrane; and the thick dermal layer of the stroma. The mucoidal layer has small collagen fiber bundles embedded in the CT layer and located between the anterior portion of the scleral cornea and the dermal stroma, (or "substancia propria"). The iridescent layer is thin at the center and thick at the periphery. It contains a pigmented layer with many ossicles. SEM analysis reveals that the cornea consists of undetermined shaped cells joined together by numerous thread-like micro-ridges, with several micro-tubercles on the external surface. The photoreceptor layer had two types of cells: the rod-shaped and the cone-shaped cells. The cone cells differentiate into two types of cells: single and double cells. SEM analysis of the retina showed that rod cells appear as thin long uniform rod-like, while the cone cells appear as rod cells with ovoid bases. SEM analysis demonstrates that the inner side of the retinal epithelium appears to be wrapped around itself. The morphological appearance of the eye adapts to life in superficial aquatic conditions. In conclusion, the current findings provide morphologic evidence to better understand the mechanism of fish vision adaptation to environmental conditions. RESEARCH HIGHLIGHTS: The transparent cornea composed of three layers; anterior stratified cuboidal epithelial, Bowman's membrane, and a thick dermal stromal layer. The mucoidal layer is formed from small collagen fibers bundles embedded in the CT layer and located between the anterior portion of the scleral cornea and the dermal stroma. There are two types of photoreceptor cells: rod and cone cells. Cone cells can be single and double cells.
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Córnea , Smegmamorpha , Animales , Colágeno , Córnea/ultraestructura , Microscopía Electrónica de Rastreo , Cemento de PolicarboxilatoRESUMEN
This study was performed to investigate the gross anatomy, histochemistry, and immunohistochemistry of the stomach in the Caucasian squirrel. A total of five male squirrels were included. The obtained results showed that the shape of the stomach was acutely crescent and consisted of four regions namely; cardiac, fundus, body, and pylorus. The stomach glandular and its wall was consisted of four layers; serosa, muscularis, submucosa, and mucosa. All part of the mucosa was covered by a simple columnar epithelium. Furthermore, gastric glands were of the simple tubular type. The mucous cells of the fundic and body regions were PAS-positive. In the lower third of the gastric glands, parietal, and chief cells were identified. The number of chief cells was increased toward the pyloric area. Scanning electron microscopy showed that the fundus region contained many plicae and grooves and each plica carried numerous glands opening. In the body region, cells were polygonal and formed network-like structures. In the pyloric region, a mucosal ridge between the body and antrum and a thick mucosal crest on the lesser curvature were identified. Immunohistochemical staining showed that Sox9 was strongly expressed in the fundic region, however, its expression in the body and pylorus was moderate to weak. In conclusion, there are some similarities and differences between the stomach of the Caucasian squirrel and other mammals including rodents. The obtained results may enhance our basic knowledge regarding the feeding habits and digestive system histophysiology of this species.
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Mucosa Gástrica , Estómago , Animales , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Histocitoquímica , Masculino , Microscopía Electrónica de Rastreo , Sciuridae , Estómago/anatomía & histologíaRESUMEN
The current study was designed to give microscopic view on the snout skin of the domestic pig (Sus scrofa domesticus) to clear its adaptations with the function of exploring for the food and pushing the objects. This study carried out on the snout skin of apparently healthy 1 year five pigs (Sus Scrofa) and examined under the light and transmission electron microscopy. Our results clarify that the snout skin cutis composed of the epidermis and the dermis. The epidermis consisted of stratum corneum, stratum granulosum, stratum spinosum, and stratum basale. The stratum corneum and the stratum spinosum appeared thicker than other parts. The dermis consisted of a reticular and a papillary dermis. For tightness junction between the dermis and the epidermis, the hemidesmosomes were observed, while the desmosomes were presented in abundant numbers at the level of stratum basale to ensure the adhesion between the keratinocytes. The merocrine sweat glands were observed in abundant numbers to provide the wetness of the snout to avoid its injury from friction during food exploring or pushing of the objects. We concluded that the adaptation of the snout skin with the environmental condition surrounding the studied domestic pig.
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Piel , Sus scrofa , Animales , Células Epidérmicas , Epidermis/ultraestructura , Microscopía Electrónica de Transmisión , PorcinosRESUMEN
The current investigation represented the first anatomical description of the buccal cavity of the grey gurnard Eutrigla gurnardus. For the achievement of this study, 10 heads of mature fish were used for SEM examinations. The morphological characteristic appearance of the buccal cavity has shown several adaptations in relation concerning its feeding habits. The median fissure of the upper lip divided the upper lip into two halves, this fissure appeared to be formed from many micro-tubercles with numerous taste buds which aid in holding mucus secretion to the cell surface, help in mucus spread, and provide mechanical protection to the epithelium. Velum had two regions: median and peripheral region. The epithelium covering of the median region of the upper velum had dots-like epithelial protrusion that carrying numerous taste buds, meanwhile, the epithelium covering of the lower velum not carried taste buds but instead carried numerous small scales-like structures. The palate is divided into two semicircular regions by small region of microridges into the anterior and posterior region. The slightly bifid tongue had a median tubercle with numerous small taste buds on its dorsal surface. Concluded, these data were necessary to understand the adaptation of fish to its habitat and in developing a new and better method for fishing of this type of fish.
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Papilas Gustativas , Lengua , Animales , Microscopía Electrónica de Rastreo , Boca , Hueso PaladarRESUMEN
SUMMARY: Amiodarone (AMD), an orally powerful antidysrhythmic medication that has caused hepatotoxicity on long-term administration, is commonly used across the world. Silymarin ameliorative effects (SLM); this research elucidated the magnitude of the damage to the liver tissue in AMD. We divided 24 albino rats evenly into four groups given daily doses by gastric tube for eight weeks as follows; the 1st group acted as a control group; the 2nd group received SLM; the 3rd group received AMD; and the 4th group received AMD parallel to SLM. Liver tissues prepared for light, electron microscopic and serum samples screened for biomarkers (I)liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); (II) oxidative and antioxidant stress, malondialdehyde (MDA) and superoxide dismutase (SOD); and (III) inflammatory markers, tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6). The findings showed that AMD caused hepatic histological changes that included congestion of the blood vessels, leucocytic infiltration and cytoplasmic vacuolation. Ultrastructural degeneration of the mitochondria, endoplasmic reticulum swelling, nuclear pyknosis and increased fat droplets and lysosomes were observed. The biochemical findings showed an increase in the AMD group's ALT and AST activities. The group of rats treated with AMD and SLM, increased the improvements in histology and ultrastructure, while the ALT and AST levels were reduced. Our findings collectively agreed that SLM has a protective impact on AMD hepatotoxicity which can be due to its antioxidant properties.
RESUMEN: La amiodarona (AMD) es un fuerte medicamento antiarrítmico administrado por vía oral que ha causado hepatotoxicidad en la administración a largo plazo utilizado con frecuencia en todo el mundo. Efectos de mejora de la silimarina (SLM); esta investigación analizó la magnitud del daño al tejido hepático en la DMAE. Dividimos 24 ratas albinas de manera uniforme en cuatro grupos que recibieron dosis diarias por sonda gástrica durante ocho semanas de la siguiente manera; el primer grupo fue designado como grupo control; el segundo grupo recibió SLM; el tercer grupo recibió AMD; y el cuarto grupo recibió AMD en paralelo a SLM. Se prepararon tejidos hepáticos para muestras de suero, microscopía de luz y electrónica y se analizaron para biomarcadores (I) enzimas de daño hepático, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST); (II) estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (III) marcadores inflamatorios, factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6). Los hallazgos mostraron que la DMAE genera cambios histológicos hepáticos que incluyen congestión de los vasos sanguíneos, infiltración leucocítica y vacuolación citoplásmica. Se observó una degeneración ultraestructural de las mitocondrias, aumento del retículo endoplásmico, picnosis nuclear y aumento de gotitas de grasa y lisosomas. Los hallazgos bioquímicos mostraron un aumento en las actividades de ALT y AST del grupo AMD. El grupo de ratas tratadas con AMD y SLM, aumentó las mejoras en histología y ultraestructura, mientras que se redujeron los niveles de ALT y AST. Nuestros hallazgos coincidieron colectivamente en que SLM tiene un impacto protector sobre la hepatotoxicidad de AMD debido a sus propiedades antioxidantes.
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Animales , Femenino , Ratas , Silimarina/administración & dosificación , Sustancias Protectoras/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Amiodarona/toxicidad , Hígado/efectos de los fármacos , Aspartato Aminotransferasas/análisis , Ratas Endogámicas , Silimarina/farmacología , Superóxido Dismutasa , Microscopía Electrónica , Interleucina-6 , Factor de Necrosis Tumoral alfa , Estrés Oxidativo , Sustancias Protectoras/farmacología , Alanina Transaminasa/análisis , Hígado/enzimología , Hígado/ultraestructura , Malondialdehído , Antiarrítmicos/toxicidadRESUMEN
The hepatotoxic impacts of 2, 4, and 8 mg/L of Al2O3 nanoparticles (31.4 ± 4.8 nm) were evaluated in Oreochromis niloticus after 7 days of exposure and 15 days of recovery periods. The biochemical analysis of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in plasma showed significant increases in both 4 and 8 mg/L Al2O3 NPs exposed groups. The antioxidant biomarkers showed concentration-dependent elevations in catalase, superoxide dismutase, glutathione peroxidase activities, and thiobarbituric acid reactive substances levels. Glutathione reduced contents showed significant reductions in both 4 and 8 mg/L Al2O3 nanoparticles exposed groups. Several hepatic histopathological alterations were recorded ranging from adaptive responses (e.g. melanomacrophages aggregation) to permanent damage (e.g. necrosis). The recovery period using toxicant-free water led to an obvious reduction in the Al content in liver, liver and antioxidant enzymes in addition to regressive histopathological alterations based on the frequency of alterations occurrence and the extent of affected areas.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Cíclidos , Nanopartículas , Óxido de Aluminio , Animales , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catalasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/veterinaria , Cíclidos/metabolismo , Hígado/metabolismo , Nanopartículas/toxicidad , Estrés Oxidativo , Superóxido Dismutasa/metabolismoRESUMEN
SUMMARY: Bisphenol A (BPA) is an industrial chemical widely used to make polycarbonate plastics for packaging and epoxy resins. This study sought to examine how selenium (Se) affects BPA toxicity in terms of albino rats' histological structure, antioxidant enzymes and reproductive organs (seminiferous tubules). Twenty-four adult male rats were divided into four experimental groups: Group 1: Control; Group 2: Orally administered BPA; Group 3: Orally administered sodium selenite; Group 4: Treated daily with BPA followed by selenium (Se). All experiment done for 4 weeks. BPA exposure caused changes in the testicular histological structure, which consists apoptosis, and led to changes in several biochemical markers: Malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase. However, these BPA side effects may be ameliorated in rats treated with BPA-plus-Se. These protective effects of Se may attributable to its ability to remove potentially damaging oxidizing agents in living organisms. The results may confirm that Se countered the oxidant effects and increased the BPA-induced stress response in rats. So, Se promotes the healthy growth and development of mammals by protecting them from oxidative stress. As human are greatly exposed to BPA and it can accumulate in tissues, there is concern about human reproductive functions particularly for occupational workers exposed usually to greater levels of BPA. Thus, the use of BPA in multiple industries must be restricted and the inaccurate usage of plastic containers should be avoided to decrease the health hazards. Administration of Se may protect against the adverse effects of BPA on reproductive functions and structures.
RESUMEN: El bisfenol A (BPA) es un químico industrial ampliamente utilizado para fabricar plásticos de policarbonato para envases y resinas epoxi. Este estudio examinó el efecto de selenio (Se) en la toxicidad del BPA en términos de la estructura histológica, enzimas antioxidantes y los órganos reproductivos (túbulos seminíferos) de ratas albinas. Se dividieron veinticuatro ratas macho adultas en cuatro grupos experimentales: Grupo 1: control; Grupo 2: BPA administrado por vía oral; Grupo 3: BPA administrado por vía oral para; Grupo 4: tratado diariamente con BPA seguido de selenio (Se). El experimento se realizó durante cuatro semanas y se observó que la exposición al BPA provocó cambios en la estructura histológica testicular, incluyendo apoptosis, y alteraciones en varios marcadores bioquímicos:malondialdehído, catalasa, superóxido dismutasa y glutatión peroxidasa. Sin embargo, estos efectos secundarios del BPA pueden mejorar en ratas tratadas con BPA-plus-Se. Estos efectos protectores del Se pueden ser atribuidos a la capacidad de eliminar agentes oxidantes potencialmente dañinos en organismos vivos. Los resultados indicaron que se contrarrestaron los efectos oxidantes y aumentó la respuesta al estrés inducido por BPA en ratas, y favorece el crecimiento y desarrollo en los mamíferos al protegerlos del estrés oxidativo. Debido a la exposición al BPA en el ser humano, se puede acumular en los tejidos, por lo que existe una preocupación por el daño a las funciones reproductivas en particular de los trabajadores que generalmente están expuestos a niveles más altos de BPA. Por lo tanto, se debe restringir el uso de BPA en las industrias y evitar el uso incorrecto de envases de plástico para así disminuir los riesgos para la salud. La administración correcta de Se puede proteger contra los efectos adversos del BPA en las funciones y estructuras reproductivas.
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Animales , Masculino , Ratas , Fenoles/toxicidad , Selenio/farmacología , Testículo/efectos de los fármacos , Compuestos de Bencidrilo/toxicidad , Antioxidantes/farmacología , Fenoles/administración & dosificación , Superóxido Dismutasa/efectos de los fármacos , Testículo/patología , Compuestos de Bencidrilo/administración & dosificación , Microscopía Electrónica , Biomarcadores , Catalasa/efectos de los fármacos , Administración Oral , Apoptosis/efectos de los fármacos , Estrés Oxidativo , Glutatión Peroxidasa/efectos de los fármacosRESUMEN
This study investigated the effect of ellagic acid (EA) on SKOV-3 cell growth and invasiveness and tested if the underlying mechanism involves modulating autophagy. Cells were treated with EA in the presence or absence of chloroquine (CQ), an autophagy inhibitor, compound C (CC), an AMPK inhibitor, or an insulin-like growth factor-1 (IGF-1), a PI3K/Akt activator. EA, at an IC50 of 36.6 µmol/L, inhibited cell proliferation, migration, and invasion and induced cell apoptosis in SKOV-3 cells. These events were prevented by CQ. Also, EA increased levels of Beclin-1, ATG-5, LC3I/II, Bax, cleaved caspase-3/8 and reduced those of p62 and Bcl-2 in these cancer cells. Mechanistically, EA decreased levels of p-S6K1 (Thr389 ) and 4EBP-1 (Thr37/46 ), two downstream targets of mTORC1, and p-Akt (Thr308 ) but increased levels of AMPK (Thr172 ) and p-raptor (Ser792 ), a natural inhibitor of mTORC1. CC or IGF-1 alone partially prevented the effect of EA on cell survival, cell invasions, and levels of LDH, Beclin-1, and cleaved caspase-3. In conclusion, EA can inhibit SKOV-3 growth, migration, and invasion by activating cytotoxic autophagy mediated by inhibition of mTORC1 and Akt and activation of AMPK.
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Proteínas Quinasas Activadas por AMP/metabolismo , Antineoplásicos Fitogénicos/farmacología , Autofagia/efectos de los fármacos , Ácido Elágico/farmacología , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Neoplasias Ováricas/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Activación Enzimática , Activadores de Enzimas/farmacología , Femenino , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Invasividad Neoplásica , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/patología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
This experiment was designed to study the administration of normal doses of one of recent antimalarial drug and coadministration of vitamin E on the kidney tissue. A total twenty-four adult male albino rats were used and divided into four groups: the first one served as a control, the second received artemether orally for three days consecutively. The rats of the third and fourth groups received the same dose of artemether concomitantly with 50 and 100 mg/kg vitamin E orally daily for 2 weeks. After the last dose, the rats were sacrificed and the kidney tissues with blood samples obtained and processed for light, electron microscopic and biochemical analysis. Histologically, artemether treated kidneys showed atrophied glomeruli with widened urinary space and kidney tubules were degenerated with disturbed contour and some vacuoles inside it. Ultrastructurally, the glomeruli of this group showed hypertrophic endothelial cells, irregularity of its basement membrane, disrupted foot processes and filtration slits. The kidney tubule cells showed loss of basal infoldings, cytoplasmic vacuolation, polymorphic damaged swollen mitochondria a loss of its microvilli towards its capillary lumen. Artemether plus vitamin E of the rat kidney groups showed improvement of morphological changes compared to the changes seen in artemether alone. These data were confirmed by biochemical findings with marked improvement of blood urea and creatinine levels and increase of anti-oxidant enzyme activities of glutathione peroxidase and superoxide dismutase in the vitamin E treated groups. The results of this study revealed that vitamins E can improve the adverse changes of artemether of rat renal tissue.
Este proyecto fue diseñado para estudiar la administración de dosis normales de uno de los medicamentos antipalúdicos y de la administración de vitamina E en el tejido renal. Se utilizaron 24 ratas albinas machos adultas divididas en cuatro grupos: el primero sirvió como control, el segundo recibió arteméter por vía oral durante tres días consecutivos. Las ratas del tercer y cuarto grupos recibieron la misma dosis de arteméter concomitantemente con 50 y 100 mg / kg de vitamina E por vía oral diariamente durante 2 semanas. Después de la última dosis, las ratas fueron sacrificadas y se obtuvo el tejido renal de cada muestra los cuales fueron procesados para análisis con microscopías de luz y electrónica, además de exámenes bioquímicos. Histológicamente, los riñones tratados con arteméter mostraron atrofia glomerular con espacio urinario ensanchado y túbulos renales degenerados con contorno alterado y algunas vacuolas en su interior. Ultraestructuralmente, los glomérulos de este grupo mostraron células endoteliales hipertróficas, irregularidad de su membrana basal, procesos alterados del pie y hendiduras de filtración. Las células del túbulo renal mostraron pérdida de inflexiones basales, vacuolación citoplasmática, mitocondrias dañadas y pérdida de sus microvellosidades hacia la luz capilar. Arteméter más vitamina E en los grupos de riñón de rata mostraron una mejora de los cambios morfológicos, en comparación con los cambios observados en arteméter solamente. Estos datos fueron confirmados por hallazgos bioquímicos con una marcada mejoría de los niveles de urea y creatinina en sangre y un aumento de las actividades enzimáticas antioxidantes de la glutatión peroxidasa y la superóxido dismutasa en los grupos tratados con vitamina E. Los resultados de este estudio revelaron que la vitamina E puede mejorar los cambios adversos del arteméter del tejido renal de la rata.