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BACKGROUND: The side effects of conventional therapeutics pose a problem for cancer treatment. Recently, combination treatments with natural compounds have attracted attention regarding limiting the side effects of treatment. Oleuropein is a natural polyphenol in olives that has antioxidant and anticancer effects. OBJECTIVES: This study aimed to investigate the oxidative stress effect of a combination of Paclitaxel, a chemotherapeutic agent, and Oleuropein in the MCF-7 cell line. METHODS: The xCELLigence RTCA method was used to determine the cytotoxic effects of Oleuropein and Paclitaxel in the MCF-7 cell line. The Total Oxidant and Total Antioxidant Status were analyzed using a kit. The Oxidative Stress Index was calculated by measuring Total Oxidant and Total Antioxidant states. The levels of superoxide dismutase, reduced glutathione and malondialdehyde, which are oxidative stress markers, were also measured by ELISA assay kit. RESULTS: As a result of the measurement, IC50 doses of Oleuropein and Paclitaxel were determined as 230 µM and 7.5 µM, respectively. Different percentages of combination ratios were generated from the obtained IC50 values. The effect of oxidative stress was investigated at the combination rates of 10%, 20%, 30%, and 40% which were determined to be synergistic. In terms of the combined use of Oleuropein and Paclitaxel on oxidative stress, antioxidant defense increased, and Oxidative Stress Index levels decreased. CONCLUSION: These findings demonstrate that the doses administered to the Oleuropein+Paclitaxel combination group were lower than those administered to groups using one agent alone (e.g. Paclitaxel), the results of which reduce the possibility of administering toxic doses.
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Neoplasias de la Mama , Glucósidos Iridoides , Paclitaxel , Humanos , Femenino , Paclitaxel/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Células MCF-7 , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Iridoides/farmacología , Estrés Oxidativo , Oxidantes/farmacología , Oxidantes/uso terapéuticoRESUMEN
BACKGROUND/AIM: Colorectal cancer (CRC) is strongly associated with altered cadherin adhesion molecules. Oxaliplatin is a standard treatment for CRC, yet high-doses have concerning side effects. In this study, the effects of oxaliplatin and the combination of oxaliplatin with vitamin C on HCT-116 CRC cell migration and invasion were studied through the roles of cellular oxidative stress associated with cadherin molecules. MATERIALS AND METHODS: The cellular assays used in this research were MTT, DCFH-DA, immunofluorescence, and western blotting. Cancer progression was examined using wound healing and Boyden chamber techniques. RESULTS: The results indicate that hydrogen peroxide-induced cellular oxidative stress induced cancer cell migration and invasion. The combined treatment of oxaliplatin with a pro-oxidant concentration of vitamin C resulted in higher toxicity than treatment with oxaliplatin alone. However, treatment with the combination of oxaliplatin and antioxidant concentrations of vitamin C suppressed cancer migration and invasion. Furthermore, the combination treatment increased E-cadherin expression, whereas decreased that of N-cadherin. CONCLUSION: Treatment with the combination of oxaliplatin with vitamin C can inhibit CRC cell growth and decrease cancer cell migration and invasion, via oxidative stress and cadherins.
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Ácido Ascórbico , Neoplasias Colorrectales , Humanos , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Ácido Ascórbico/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Oxidantes/farmacología , Oxidantes/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Cadherinas/metabolismo , Movimiento CelularRESUMEN
Background: Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure syndrome with diverse etiologies characterized by increased permeability of alveolar-capillary membranes, pulmonary edema, and acute onset hypoxemia. During the ARDS acute phase, neutrophil infiltration into the alveolar space results in uncontrolled release of reactive oxygen species (ROS) and proteases, overwhelming antioxidant defenses and causing alveolar epithelial and lung endothelial injury. Objectives: To investigate the therapeutic potential of a novel recombinant human Cu-Zn-superoxide dismutase (SOD) fusion protein in protecting against ROS injury and for aerosolized SOD delivery to treat Escherichia coli induced ARDS. Methods: Fusion proteins incorporating human Cu-Zn-SOD (hSOD1), with (pep1-hSOD1-his) and without (hSOD1-his) a fused hyaluronic acid-binding peptide, were expressed in E. coli. Purified proteins were evaluated in in vitro assays with human bronchial epithelial cells and through aerosolized delivery to the lung of an E. coli-induced ARDS rat model. Results: SOD proteins exhibited high SOD activity in vitro and protected bronchial epithelial cells from oxidative damage. hSOD1-his and pep1-hSOD1-his retained SOD activity postnebulization and exhibited no adverse effects in the rat. Pep1-hSOD1-his administered through instillation or nebulization to the lung of an E. coli-induced pneumonia rat improved arterial oxygenation and lactate levels compared to vehicle after 48 hours. Static lung compliance was improved when the pep1-hSOD1-his protein was delivered by instillation. White cell infiltration to the lung was significantly reduced by aerosolized delivery of protein, and reduction of cytokine-induced neutrophil chemoattractant-1, interferon-gamma, and interleukin 6 pro-inflammatory cytokine concentrations in bronchoalveolar lavage was observed. Conclusions: Aerosol delivery of a novel recombinant modified SOD protein reduces oxidant injury and attenuates E. coli induced lung injury in rats. The results provide a strong basis for further investigation of the therapeutic potential of hSOD1 in the treatment of ARDS.
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Lesión Pulmonar , Neumonía Bacteriana , Síndrome de Dificultad Respiratoria , Ratas , Humanos , Animales , Lesión Pulmonar/tratamiento farmacológico , Escherichia coli , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/uso terapéutico , Oxidantes/metabolismo , Oxidantes/uso terapéutico , Administración por Inhalación , Aerosoles y Gotitas Respiratorias , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/farmacología , Superóxido Dismutasa/uso terapéutico , Pulmón/metabolismo , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/metabolismo , Neumonía Bacteriana/tratamiento farmacológico , Citocinas/metabolismo , Citocinas/uso terapéuticoRESUMEN
Transcranial direct curent stimulation (tDCS) and trans-spinal direct current stimulation (tsDCS) are promising therapies for pain that can alter the excitability of neuronal activity in cerebral cortex. The aim of the study is to investigate the therapeutic effects of direct current stimulation (DCS) over the spinal cord and cerebral cortex on oxidative stress and neuroinflammation in rats with chronic constriction injury (CCI). Male Wistar rats were randomly divided into four experimental groups: Sham, CCI, CCI + tDCS and CCI + tsDCS. The neuropathic pain model was induced by using the CCI model. Rats with neuropathy were treated with cathodal tDCS and tsDCS stimulations consisting of 0.5 mA for 30 min a day for 7 days from day 8 onwards. Locomotor activity was measured by open-field test and nociceptive behavior was assessed by hot-plate, tail-flick and Randall-Selitto tests. Following the behavioral experiments, total oxidant capacity (TOC), total antioxidant capacity (TAC) and proinflammatory cytokine levels were evaluated in spinal cord and cerebral cortex tissues. The CCI model induced significant mechanical and thermal hyperalgesia. Nociceptive behaviors in rats with CCI were reversed by DCS treatment. Higher TOC and lower TAC levels were detected in the spinal cord and cerebral cortex tissues of the CCI rats compared to the control. tsDCS treatment amended oxidant/antioxidant status. Moreover, tsDCS modulated the central levels of Tumor necrosis factor-α (TNF-α), interleukin 1-beta (IL-1ß), IL-6 and IL-18. tsDCS stimulation showed better therapeutic effect on neuropathic pain by regulating oxidant/antioxidant levels and reducing neuroinflammation. DCS, especially at spinal level, may be a promising therapeutic strategy that can be used alone or in combination with other effective treatments for alleviating neuropathic pain.
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Neuralgia , Estimulación Transcraneal de Corriente Directa , Ratas , Masculino , Animales , Ratas Wistar , Antioxidantes/uso terapéutico , Enfermedades Neuroinflamatorias , Nocicepción , Nervio Ciático , Neuralgia/terapia , Neuralgia/patología , Hiperalgesia/tratamiento farmacológico , Médula Espinal/patología , Estrés Oxidativo , Oxidantes/farmacología , Oxidantes/uso terapéuticoRESUMEN
BACKGROUND: Sepsis is a complex syndrome which comes out after infection, characterized by activation of inflammation and infection and has a high morbidity and mortality. Sildenafil (SLD) is a selective phosphodiesterase Type 5 enzyme inhibitor and is used in the treatment of erectile dysfunction effectively all over the world. In this study, we investigated whether SLD had protective effect or not by studying the effect of SLD on reactive oxygen species and antioxidants in cecal ligation and puncture (CLP) polymicrobial sepsis model in rat liver histopathologically and biochemically. METHODS: Rats were divided into four groups: (1) 10 mg/kg SLD given CLP group; (2) 20 mg/kg SLD given CLP group; (3) CLP group; and (4) SHAM operated group. CLP polymicrobial sepsis model was applied to the rats. All rats in our study were sacrificed by overdose general anesthetic after 16 h (thiopental sodium, 50 mg/kg). Specimens of rat liver were analyzed histopathologically and biochemically. In the study, superoxide dismutase (SOD) and glutathione (GSH) parameters were measured to indicate the antioxidant activity in liver during sepsis. To evaluate the oxidant activity, myeloperoxidase (MPO) and lipid peroxidation (LPO) parameters were measured in liver tissue. RESULTS: SOD and MPO activities and GSH and LPO levels were high in CLP polymicrobial sepsis model when compared to SHAM group (p<0.05). In all SLD groups, GSH levels were high when compared to CLP group. In 20 mg/kg SLD given sepsis group, high GSH levels were observed according to SHAM group. In addition, while all SLD dose groups had a significant decrease versus CLP group in LPO levels (p<0.05), they had a significant increase in MPO activities. In 20 mg/kg SLD administrated rats, an improvement observed in biochemical parameters. In this study, SOD and MPO activities which were low in SHAM group increased in CLP polymicrobial sepsis model. When SLD administrated, MPO activity increased in both SHAM and CLP groups. In this study, GSH and LPO levels also increase in septic liver tissue. When SLD administrated to SHAM group, it increased VI protective GSH level and decreased detrimental LPO level. In histopathological examination, it was observed that 10 mg/kg SLD administration had a curative effect in liver tissue partly. CONCLUSION: It was shown that acute SLD administration decreased liver damage in septic rats dose-dependently in this study. In addition, it was observed that it corrected the broken oxidant-antioxidant balance. This might mediate the protective effect of SLD in liver. However, we believe that new experimental and clinical studies should be in the future to understand the protective effect of SLD in liver.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Sepsis , Masculino , Ratas , Animales , Citrato de Sildenafil/farmacología , Ratas Wistar , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Glutatión , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Superóxido Dismutasa/uso terapéutico , Oxidantes/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Glioblastoma multiform (GBM) is a malignant tumor cancer that originates from the star-shaped glial support tissues, namely astrocytes, and it is associated with a poor prognosis in the brain. The GBM has no cure, and chemotherapy, radiation therapy, and immunotherapy are all ineffective. A certain dose of Boric acid (BA) has many biochemical effects, conspicuously over antioxidant/oxidant rates. This article sought to investigate the modifies of various doses of BA on the glioblastoma concerning cytotoxicity, ferroptosis, apoptosis, and semaphorin-neuropilin signaling pathway. The Cytotoxic activity and cell viability of BA (0.39-25 mM) in C6 cells were tested at 24, 48, and 72 h using 3-(4,5-dimethylthiazol, 2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The IC50 concentration of BA at 1.56 mM was found and cell lysate used for biochemical analysis. Glutathione peroxidase 4 (GPx4) and ACLS4 levels of ferroptosis, levels of total antioxidant (TAS) and oxidant (TAS) parameters, malondialdehyde (MDA), apoptotic proteins as caspase 3 (CASP3) and caspase 7 (CASP7) were measured. The ferroptosis, semaphoring-neuropilin, apoptotic pathway markers and cell counts were analyzed with flow cytometry, Q-PCR, Western and Elisa technique in the C6 cell lysate. BA triggered ferroptosis in the C6 cells dose-dependently, affecting the semaphorin pathway, so reducing proliferation with apoptotic compared with untreated cell as control group (p < .05). This study revealed that BA, defined as trace element and natural compound, incubated ferroptosis, total oxidant molecules, and caspase protein in a dose-dependently by disrupting SEMA3F in tumor cells.
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Ferroptosis , Glioblastoma , Semaforinas , Humanos , Glioblastoma/patología , Boro/farmacología , Boro/uso terapéutico , Antioxidantes/farmacología , Línea Celular Tumoral , Transducción de Señal , Oxidantes/farmacología , Oxidantes/uso terapéutico , Semaforinas/farmacología , Semaforinas/uso terapéutico , Neuropilinas , Proteínas de la Membrana , Proteínas del Tejido NerviosoRESUMEN
The present study was conducted to investigate the immunomodulatory and anti-inflammatory effects of Elettaria cardamomum essential oil (ECEO) for the control of acute Toxoplasma gondii infection. The effect of ECEO on T. gondii tachyzoites was measured by the tetrazolium bromide method. Mice received ECEO orally at doses of 1-4 mg/kg/day for 14 days. Once acute toxoplasmosis was induced in mice, their mortality rate and parasite load were recorded. The level of liver antioxidant/oxidant enzymes and the level of mRNA expression of interleukin-1 beta and interferongamma were also investigated. ECEO particularly at a concentration of 150 µg/ml has promising in vitro anti-Toxoplasma effects (p<0.001). After treatment with ECEO, the mortality rate (9th day) and parasite load decreased (p<0.001) in the infected mice. ECEO markedly (p < 0.05) restored hepatic oxidant and antioxidant enzyme levels, as well as increased cytokines. These results report a significant inhibitory effect of ECEO mainly at a dose of 4 mg/mL, against the T. gondii Rh strain through strengthening the immune system and reducing inflammation and oxidative stress; however, further research is needed to verify these results.
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Elettaria , Aceites Volátiles , Toxoplasma , Toxoplasmosis , Animales , Ratones , Antioxidantes/farmacología , Toxoplasma/genética , Antiinflamatorios/farmacología , Oxidantes/farmacología , Oxidantes/uso terapéutico , Aceites Volátiles/farmacologíaRESUMEN
A study by Tcyganov et al.1 demonstrates that peroxynitrite, an oxidant abundant in the tumor microenvironment, changes the repertoire of MHC class I peptides presented by tumors and limits immune recognition. Peroxynitrite inhibition in combination with immune checkpoint blockade enhances efficacy preclinically.
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Evasión Inmune , Neoplasias , Humanos , Ácido Peroxinitroso/uso terapéutico , Inhibidores de Puntos de Control Inmunológico , Antígenos de Neoplasias/uso terapéutico , Antígenos de Histocompatibilidad Clase I , Neoplasias/tratamiento farmacológico , Péptidos/uso terapéutico , Oxidantes/uso terapéutico , Microambiente TumoralRESUMEN
OBJECTIVES: Hyperhomocysteinemia (HHcy) can induce vascular inflammatory and oxidative damage and accelerate intimal hyperplasia. This study investigated the protective effect of pirfenidone (PFD) on the recovery process of injured endothelial arteries during HHcy. MATERIALS AND METHODS: Thirty rabbits were randomly separated into three groups: A control group (n=10, standard rabbit chow), a model group (n=10, control diet plus 30 g methionine/kg food), and a PFD group (n=10, model diet plus oral administration of 90 mg/day of PFD). After 14 weeks of arterial injury, histopathological changes were determined. Plasma homocysteine (Hcy) concentrations, lipid profiles and oxidant and antioxidant status were evaluated. Macrophage infiltration was assessed using immunohistochemical staining. RESULTS: PFD supplementation decreased macrophage infiltration of iliac artery significantly without changes in blood lipids and Hcy concentrations. Compared with the model group, PFD restored superoxide dismutase and glutathione peroxidase activities and reduced malondialdehyde and reactive oxygen species levels. A high-methionine diet significantly increased neointimal area and the ratio between neointimal and media area. Systemic administration of PFD inhibited neointimal formation. CONCLUSIONS: PFD can partly alleviate intimal hyperplasia by inhibiting inflammatory and oxidative stress response induced by HHcy during endothelial injury. It may be a potential therapeutic agent for the prevention and treatment of endothelial injury-associated diseases such as atherosclerosis.
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Hiperhomocisteinemia , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Glutatión Peroxidasa/farmacología , Glutatión Peroxidasa/uso terapéutico , Homocisteína/farmacología , Homocisteína/uso terapéutico , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/tratamiento farmacológico , Hiperhomocisteinemia/patología , Hiperplasia/patología , Lípidos , Malondialdehído/farmacología , Metionina/farmacología , Metionina/uso terapéutico , Oxidantes/farmacología , Oxidantes/uso terapéutico , Piridonas , Conejos , Especies Reactivas de Oxígeno/farmacología , Especies Reactivas de Oxígeno/uso terapéutico , Superóxido Dismutasa/farmacología , Superóxido Dismutasa/uso terapéutico , Túnica Íntima/patologíaRESUMEN
Sickle cell disease is an inherited blood disorder afflicting an estimated 100,000 individuals in the United States and over 20 million people worldwide. The disease is heralded as the first molecular disease. However, despite its genetic simplicity, the pathophysiologic processes leading to its clinical sequelae are complex, heterogeneous and interrelated, making drug development to treat the disease challenging. For over two decades only one drug, hydroxyurea, had been used as disease-modifying therapy. New pharmacologic agents are rapidly evolving with three new drugs, with different mechanisms of action, approved by the United States Food and Drug Administration in recent years (L-glutamine, crizanlizumab and voxelotor). Several therapeutic approaches targeting different pathways in the disease pathophysiology are being investigated. These include inhibition of hemoglobin S polymerization such as by fetal hemoglobin induction or by increasing hemoglobin oxygen affinity, as well as intervention of downstream pathways including inhibiting cellular adhesion, reducing inflammation and oxidant stress, modulating platelet activation and coagulation abnormalities, and targeting nitric oxide signaling. This review will provide an overview of these therapeutic strategies, discuss the four currently approved drugs in detail, and summarize ongoing clinical trials of new drugs or drug indications for the treatment of sickle cell disease in different phases of development excluding those related to cellular therapies.
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Anemia de Células Falciformes , Hidroxiurea , Humanos , Estados Unidos , Hidroxiurea/farmacología , Hidroxiurea/uso terapéutico , Hemoglobina Falciforme/metabolismo , Hemoglobina Fetal/uso terapéutico , Glutamina/uso terapéutico , Óxido Nítrico/uso terapéutico , Anemia de Células Falciformes/terapia , Hemoglobinas , Oxidantes/uso terapéutico , OxígenoRESUMEN
BACKGROUND AND OBJECTIVE: Bone loss occurs in several inflammatory diseases because of chronic persistent inflammation that activates osteoclasts (OCs) to increase bone resorption. Currently available antiresorptive drugs have severe side effects or contraindications. Herein, we explored the effects and mechanism of Alpinetin (Alp) on receptor activator of nuclear factor κB ligand (RANKL)-mediated OCs differentiation, function, and in inflammatory osteolysis of mice. METHOD: Primary mouse bone marrow-derived macrophages (BMMs) induced by RANKL and macrophage colony-stimulating factor (M-CSF) were utilized to test the impact of Alp on OCs differentiation, function, and intracellular reactive oxygen species (ROS) production, respectively. Expression of oxidant stress relevant factors and OCs specific genes were assessed via real-time quantitative PCR. Further, oxidative stress-related factors, NF-κB, MAPK, PI3K/AKT/GSK3-ß, and NFATc1 pathways were examined via Western blot. Finally, LPS-induced mouse calvarial osteolysis was used to investigate the effect of Alp on inflammatory osteolysis in vivo. RESULT: Alp suppressed OCs differentiation and resorption function, and down-regulated the ROS production. Alp inhibited IL-1ß, TNF-α and osteoclast-specific gene transcription. It also blocked the gene and protein expression of Nox1 and Keap1, but enhanced Nrf2, CAT, and HO-1 protein levels. Additionally, Alp suppressed the phosphorylation of PI3K and P38, and restrained the expression of osteoclast-specific gene Nfatc1 and its auto-amplification, hence minimizing LPS-induced osteolysis in mice. CONCLUSION: Alp is a novel candidate or therapeutics for the osteoclast-associated inflammatory osteolytic ailment.
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Conservadores de la Densidad Ósea , Osteólisis , Animales , Conservadores de la Densidad Ósea/farmacología , Diferenciación Celular , Flavanonas , Glucógeno Sintasa Quinasa 3/metabolismo , Inflamación/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Lipopolisacáridos/farmacología , Factor Estimulante de Colonias de Macrófagos/metabolismo , Factor Estimulante de Colonias de Macrófagos/farmacología , Factor Estimulante de Colonias de Macrófagos/uso terapéutico , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Osteoclastos , Osteólisis/inducido químicamente , Osteólisis/tratamiento farmacológico , Oxidantes/metabolismo , Oxidantes/farmacología , Oxidantes/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ligando RANK/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
PURPOSE: To assess effects of a novel hydrogen peroxide leave-on whitening emulsion on surface hardness, fracture susceptibility, surface erosion, and surface morphology of enamel and dentin. METHODS: Human enamel and root dentin sections embedded in resin were leveled and polished for uniformity. A cycling treatment simulating overuse conditions (60 hours over 10 days), coupled with incubation in pooled human saliva at 37°C and two daily toothpaste treatments were used to evaluate the safety of a 3% hydrogen peroxide whitening emulsion treatment (Crest Whitening Emulsions). Controls included a no treatment group, three erosion controls (water, 0.25% citric acid pH 3.6, 1% citric acid pH 3.6), and a bleaching control (8.25% sodium hypochlorite). Color measurements (b*) were taken on select post-treated specimens to confirm bleaching activity. Effects on enamel and dentin physical properties were determined by surface microhardness, fracture toughness, erosion depth, and surface morphology by light and scanning electron microscopy. RESULTS: The hydrogen peroxide emulsion b* value was significantly different versus water control (P< 0.05), confirming bleaching activity. Microhardness and fracture toughness results for hydrogen peroxide emulsions were not significantly different versus baseline (P> 0.2) and no treatment (P= 1.0), respectively. Erosion loss for the hydrogen peroxide emulsion was not observed on enamel (comparable to water) and significantly less than 0.25% citric acid (P< 0.05) on dentin which was verified by microscopic visualization. CLINICAL SIGNIFICANCE: The hydrogen peroxide emulsion had no significant negative effects on enamel and dentin properties after 60 hours of bleaching over 10 days, confirming safety under simulated overuse conditions.
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Peróxido de Hidrógeno , Blanqueamiento de Dientes , Ácido Cítrico/efectos adversos , Ácido Cítrico/análisis , Esmalte Dental , Dentina , Dureza , Humanos , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/uso terapéutico , Oxidantes/farmacología , Oxidantes/uso terapéutico , Tecnología , Blanqueamiento de Dientes/efectos adversos , Blanqueamiento de Dientes/métodos , Agua/análisis , Agua/farmacologíaRESUMEN
INTRODUCTION: Atherosclerosis can be considered a chronic inflammatory process that stands out as a dominant cause of cardiovascular disease (CVD). Since blood lipids are the leading risk factor for atherosclerosis development, lowering low-density lipoprotein cholesterol (LDL-C) and other apolipoprotein B-containing lipoproteins reduces the risk of future cardiovascular events. However, there has been significant progress in developing lipid-lowering drugs for aggressive management of dyslipidemia, the rates of CVD events remain unacceptably high, so there is great need to identify novel therapeutic pathways targeting the atherosclerosis process. AREAS COVERED: We discussed the current guidelines on CVD prevention, the role of novel lipid-lowering drugs, as well as emerging drugs for atherosclerosis, emphasizing the current data on compounds targeting inflammatory and oxidant pathways. EXPERT OPINION: Although novel lipid-lowering drugs all showed their therapeutic efficacy in LDL-C lowering, data regarding their impact on cardiovascular outcomes is still inconclusive. On the other hand, some of the agents targeting inflammatory pathways, especially colchicine, showed promising results in terms of reducing CVD events. In contrast, those pointed at oxidant pathways failed to do so. Finally, exploring ways of targeting new therapeutic venues, such as adaptive immunity and clonal hematopoiesis, is a goal in the future.
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Aterosclerosis , Enfermedades Cardiovasculares , Dislipidemias , Aterosclerosis/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol , Dislipidemias/tratamiento farmacológico , Humanos , Lípidos , Oxidantes/uso terapéuticoRESUMEN
OBJECTIVE: The aims of our experiment were to compare the microorganisms in meibomian gland secretions from patients with internal hordeolum before and after treatment using hypochlorous acid eyelid wipes, to elucidate the mechanism underlying hypochlorous acid eyelid wipe treatment of internal hordeolum. METHODS: This was a prospective, matched-pair study. A total of eight patients with internal hordeolum who attended the ophthalmology clinic of our hospital from April to August 2020 were included. Meibomian gland secretions were collected from subjects before treatment (Group A) and from patients cured after eyelid cleaning with hypochlorous acid eyelid wipes for 7 days (Group B). Samples were submitted to 16S rRNA high-throughput sequencing, and the resulting data were analyzed to compare the differences in the structure and composition of meibomian gland secretion microbial flora before and after treatment of internal hordeolum. RESULTS: A total of 2127 operational taxonomic units were obtained from the two groups of samples, and there was no significant difference in alpha diversity before and after eyelid cleaning. At the phylum level, there was no significant difference between the two groups. The predominant phyla in Group A included the following: Firmicutes (32.78% ± 20.16%), Proteobacteria (26.73% ± 7.49%), Acidobacteria (10.58% ± 11.45%), Bacteroidetes (9.05% ± 6.63%), Actinobacteria (8.48% ±1.77%), and Chloroflexi (3.15% ± 3.12%), while those in Group B were the following: Proteobacteria (31.86% ± 9.69%), Firmicutes (29.07% ± 24.20%), Acidobacteria (11.33% ± 7.53%), Actinobacteria (7.10% ± 1.98%), Bacteroidetes (5.39% ± 5.17%), and Chloroflexi (3.89% ± 3.67%). Starting from the class level, significant differences in microbial communities were detected before and after eyelid cleaning (P < 0.05). Linear discriminant analysis effect size analysis showed the core flora in Group A microbiome comprising Actinobacteria, Staphylococcus, Staphylococcaceae, Staphylococcus aureus, Ruminococcacea UCg-014, Ruminococcacea-UCG-014, Halomonadaceae, Neisseria, Methylobacterium, Frankiales, and Neisseria sicca, while those in Group B microbial were Streptococcus sp., Blautia, Bifidobacterium pseudocatenulatum, Subdoligranulum, Subdoligranulum variabile, Faecalibacterium, and Faecalibacterium prausnitzii. CONCLUSION: Eyelid cleaning with hypochlorous acid eyelid wipes does not change the biodiversity in the meibomian gland secretions of patients with internal hordeolum. Hypochlorous acid eyelid wipes may affect the internal hordeolum through broad-spectrum antibacterial action to effectively reduce the relative abundance of symbiotic pathogens, such as Staphylococcus, Neisseria, Actinomycetes, and Ruminococcus and increase that of Faecalibacterium prausnitzii and other symbiotic probiotics with anti-inflammatory effects.
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Bacterias/genética , Orzuelo/tratamiento farmacológico , Ácido Hipocloroso/uso terapéutico , Glándulas Tarsales/microbiología , Microbiota , Oxidantes/uso terapéutico , Adulto , Biodiversidad , Femenino , Humanos , Masculino , Estudios Prospectivos , ARN Ribosómico 16S/genéticaRESUMEN
The aim of this experimental animal study was to investigate the histopathological and biochemical efficacy of trimetazidine (TMZ) in decreasing ovary damage in an ovary ischaemia/reperfusion (I/R) model in the rat. A total of 35 Wistar albino female rats were randomly separated into five groups, n = 7 per group: Group 1: Sham (S) was only given a laparotomy procedure. Group 2: Ischaemia (I) group with 2-hour ischaemia using a vascular sutur. Group 3: Ischaemia/Reperfusion (I/R) group with 2 hour ischaemia and 2-hour reperfusion. Group 4: Sham + 10 mg/kg orally TMZ (S + TMZ). Group 5: I/R + 10 mg/kg oral TMZ (I/R + TMZ) group with 2 hours ischaemia and 2 hours reperfusion after the administration orally 10 mg/kg oral TMZ. Two daily doses of TMZ were orally administered to Group 4 (S + TMZ) and Group 5 (I/R + TMZ) for three days. TMZ significantly decreased vascular congestion, haemorrhage, and polymorphonuclear leukocyte infiltration in group 5 compared to group 3 (p < .05). Despite TMZ decreased the malondialdehyde, total oxidant status, and oxidative stress index values, these decreases were not statistically significant (p > .05). TMZ which is an antioxidant agent can efficiently prevent in I/R damage in rat ovaries but further studies are necessary in order to implement it in the clinical settings.IMPACT STATEMENTWhat is already known on this subject? Adnexial torsion is the most common gynecological emergency and there are no specific clinical, laboratories, or radiological findings for adnexal torsion. Unfortunatelly, the currently accepted treatment is adnexal detorsion. Cytoprotective effects of Trimetazidine (TMZ), an antianginal drug, are well-defined and it has been demonstrated to improve oxidative stress markers and limits membrane damage induced by reactive oxygen species and protects tissues from free radicals with its antioxidant effects. The aim of this study is to investigate the effects of TMZ in experimentally induced adnexal torsion in rats and to investigate possible effects in maintaining ovarian reserve to prevent I/R damage or reperfusion damage.What do the results of this study add? Our study showed that TMZ significantly decreased vascular congestion, haemorrhage, and PMNL infiltration. TMZ decreased the malondialdehyde, total oxidant status, and the oxidative stress index values, but these decreases were not statistically significant.What are the implications of these findings for clinical practice and/or further research? Although various antioxidant drugs and chemicals have been used to protect the ovaries against I/R damage, they have not been demostrated to prevent it completely. TMZ, an antioxidant efficacy agent, has been shown to prevent ovarian I/R damage by suppressing inflammation in terms of histopathological parameters. Further studies involving a greater number of experimental animals are required before using TMZ for the treatment of humans with I/R damage in the clinical setting.
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Enfermedades del Ovario , Daño por Reperfusión , Trimetazidina , Animales , Femenino , Humanos , Ratas , Antioxidantes/farmacología , Isquemia/tratamiento farmacológico , Malondialdehído , Enfermedades del Ovario/patología , Torsión Ovárica/tratamiento farmacológico , Oxidantes/uso terapéutico , Ratas Wistar , Especies Reactivas de Oxígeno , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Trimetazidina/farmacología , Trimetazidina/uso terapéuticoRESUMEN
Chronic inhalation of cigarette smoke is a prominent cause of chronic obstructive pulmonary disease (COPD) and provides an important source of exogenous oxidants. In addition, several inflammatory and structural cells are a source of endogenous oxidants in the lower airways of COPD patients, even in former smokers. This suggests that oxidants play a key role in the pathogenesis of COPD. This oxidative stress is counterbalanced by the protective effects of the various endogenous antioxidant defenses of the lower airways. A large amount of data from animal models and patients with COPD have shown that both the stable phase of the disease, and during exacerbations, have increased oxidative stress in the lower airways compared with age-matched smokers with normal lung function. Thus, counteracting the increased oxidative stress may produce clinical benefits in COPD patients. Smoking cessation is currently the most effective treatment of COPD patients and reduces oxidative stress in the lower airways. In addition, many drugs used to treat COPD have some antioxidant effects, however, it is still unclear if their clinical efficacy is related to pharmacological modulation of the oxidant/antioxidant balance. Several new antioxidant compounds are in development for the treatment of COPD.
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Antioxidantes , Enfermedad Pulmonar Obstructiva Crónica , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Humanos , Oxidantes/uso terapéutico , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/patología , FumadoresRESUMEN
Changes in reactive oxygen species (ROS) levels affect many aspects of cell behavior. During carcinogenesis, moderate ROS production modifies gene expression to alter cell function, elevating metabolic activity and ROS. To avoid extreme ROS-activated death, cancer cells increase antioxidative capacity, regulating sustained ROS levels that promote growth. Anticancer therapies are exploring inducing supranormal, cytotoxic oxidative stress levels either inhibiting antioxidative capacity or promoting excess ROS to selectively destroy cancer cells, triggering mechanisms such as apoptosis, autophagy, necrosis, or ferroptosis. This review exemplifies pro-oxidants (natural/synthetic/repurposed drugs) and their clinical significance as cancer therapies providing revolutionary approaches.
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Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias/tratamiento farmacológico , Oxidantes/farmacología , Humanos , Oxidantes/uso terapéutico , Oxidación-ReducciónRESUMEN
Reactive oxygen species play crucial role in biological homeostasis and pathogenesis of human diseases including cancer. In this line, now it has become evident that ROS level/concentration is a major factor in the growth, progression and stemness of cancer cells. Moreover, cancer cells maintain a delicate balance between ROS and antioxidants to promote pathogenesis and clinical challenges via targeting a battery of signaling pathways converging to cancer hallmarks. Recent findings also entail the therapeutic importance of ROS for the better clinical outcomes in cancer patients as they induce apoptosis and autophagy. Moreover, poor clinical outcomes associated with cancer therapies are the major challenge and use of natural products have been vital in attenuation of these challenges due to their multitargeting potential with less adverse effects. In fact, most available drugs are derived from natural resources, either directly or indirectly and available evidence show the clinical importance of natural products in the management of various diseases, including cancer. ROS play a critical role in the anticancer actions of natural products, particularly phytochemicals. Benzophenanthridine alkaloids of the benzyl isoquinoline family of alkaloids, such as sanguinarine, possess several pharmacological properties and are thus being studied for the treatment of different human diseases, including cancer. In this article, we review recent findings, on how benzophenanthridine alkaloid-induced ROS play a critical role in the attenuation of pathological changes and stemness features associated with human cancers. In addition, we highlight the role of ROS in benzophenanthridine alkaloid-mediated activation of the signaling pathway associated with cancer cell apoptosis and autophagy.
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Antineoplásicos/uso terapéutico , Benzofenantridinas/uso terapéutico , Neoplasias/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Oxidantes/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagia/efectos de los fármacos , Proteínas Relacionadas con la Autofagia/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Transducción de SeñalRESUMEN
Acute lymphoblastic leukemia (ALL) is a hematological malignancy originating from B- or T-lymphoid progenitor cells. Recent studies have shown that redox dysregulation caused by overproduction of reactive oxygen species (ROS) has an important role in the development and progression of leukemia. The application of pro-oxidant therapy, which targets redox dysregulation, has achieved satisfactory results in alleviating the conditions of and improving the survival rate for patients with ALL. However, drug resistance and side effects are two major challenges that must be addressed in pro-oxidant therapy. Oxidative stress can activate a variety of antioxidant mechanisms to help leukemia cells escape the damage caused by pro-oxidant drugs and develop drug resistance. Hematopoietic stem cells (HSCs) are extremely sensitive to oxidative stress due to their low levels of differentiation, and the use of pro-oxidant drugs inevitably causes damage to HSCs and may even cause severe bone marrow suppression. In this article, we reviewed research progress regarding the generation and regulation of ROS in normal HSCs and ALL cells as well as the impact of ROS on the biological behavior and fate of cells. An in-depth understanding of the regulatory mechanisms of redox homeostasis in normal and malignant HSCs is conducive to the formulation of rational targeted treatment plans to effectively reduce oxidative damage to normal HSCs while eradicating ALL cells.
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Células Madre Hematopoyéticas/metabolismo , Estrés Oxidativo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Antineoplásicos/uso terapéutico , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/patología , Humanos , Terapia Molecular Dirigida , Oxidantes/uso terapéutico , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Carvacrol effects on inflammatory mediators, lung pathology and tracheal responsiveness were indicated in animal models of pulmonary diseases. PURPOSE: To evaluate carvacrol effects on respiratory symptoms, pulmonary function tests (PFT), oxidative stress markers and cytokine levels in asthmatic patients. STUDY DESIGN: This study was a randomized, placebo-controlled double-blind, clinical trial. METHODS: Thirty-three moderate asthmatic patients were divided to the two groups of: placebo group (n = 16) and carvacrol group (1.2 mg/kg/day, n = 17). Prepared capsules were taken for two months along, 3 times/day along with routine medications. Respiratory symptoms, PFT, and oxidative stress markers were evaluated before the treatment (step 0), and one (step I) and two months (step II) after the beginning of the treatment. However, cytokine levels in serum and supernatant of peripheral blood mononuclear cells (PBMC), and their gene expression were evaluated in step 0 and II. RESULTS: In carvacrol-treated group, respiratory symptoms significantly decreased after one- and two-month treatment with carvacrol compared to pre-treatment values (p < 0.05 to p < 0.001). Compared to step 0, PFT values were significantly increased in step I and II, in treated group with carvacrol (p < 0.05 to p < 0.001). Most oxidative stress markers were improved following carvacrol treatment (p < 0.05 to p < 0.001). Treatment with carvacrol for two-month also significantly improved cytokine levels in serum and supernatant of PBMC, compared to step 0 (p < 0.05 to p < 0.001). However, no significant changes were observed in the above-noted parameters in the placebo group. CONCLUSION: Due to anti-inflammatory and antioxidant effect, carvacrol could be suggested as a therapeutic agent for asthma.