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1.
J Appl Oral Sci ; 28: e20190384, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520077

RESUMO

OBJECTIVES: This study evaluated if the use of a bioactive glass-ceramic-based gel, named Biosilicate (BS), before, after or mixed with bleaching gel, could influence the inflammation of the dental pulp tissue of rats' molars undergoing dental bleaching with hydrogen peroxide (H2O2). METHODOLOGY: The upper molars of Wistar rats (Rattus norvegicus, albinus) were divided into Ble: bleached (35% H2O2, 30-min); Ble-BS: bleached and followed by BS-based gel application (20 min); BS-Ble: BS-based gel application and then bleaching; BS/7d-Ble: BS-based gel applications for 7 days and then bleaching; Ble+BS: blend of H2O2 with BS-based gel (1:1, 30-min); and control: placebo gel. After 2 and 30 days (n=10), the rats were euthanized for histological evaluation. The Kruskal-Wallis and Dunn statistical tests were performed (P<0.05). RESULTS: At 2 days, the Ble and Ble-BS groups had significant alterations in the pulp tissue, with an area of necrosis. The groups with the application of BS-based gel before H2O2 had moderate inflammation and partial disorganization in the occlusal third of the coronary pulp and were significantly different from the Ble in the middle and cervical thirds (P<0.05). The most favorable results were observed in the Ble+BS, which was similar to the control in all thirds of the coronary pulp (P>0.05). At 30 days, the pulp tissue was organized and the bleached groups presented tertiary dentin deposition. The Ble group had the highest deposition of tertiary dentin, followed by the Ble-BS, and both were different from control (P<0.05). CONCLUSION: A single BS-based gel application beforehand or BS-based gel blended with a bleaching gel minimize the pulp damage induced by dental bleaching.


Assuntos
Polpa Dentária/efeitos dos fármacos , Vidro/química , Peróxido de Hidrogênio/química , Pulpite/prevenção & controle , Clareadores Dentários/química , Clareamento Dental/métodos , Animais , Polpa Dentária/patologia , Peróxido de Hidrogênio/efeitos adversos , Masculino , Dente Molar , Pulpite/induzido quimicamente , Pulpite/patologia , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Clareamento Dental/efeitos adversos , Clareadores Dentários/efeitos adversos , Resultado do Tratamento
2.
Int J Med Mushrooms ; 22(2): 183-195, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479006

RESUMO

The objective of this study was to explore the effect of magnesium acetate (MA) addition on the endo-polyphenol yield by Phellinus baumii and establish a feasible additive strategy. The optimal three-point MA addition strategy (0.05 g/L concentration of MA added at 0 h and 6 h, 0.9 g/L concentration of MA added at 12 h) was employed to obtain maximum endo-polyphenol yield. The maximum endo-polyphenol production was reached at 1.22 g/L, which was 1.39-fold higher than that of the control. Additionally, the endo-polyphenol showed stronger antioxidant activity in vitro compared with the control, including DPPH· scavenging capacity (78.76%) and Trolox equivalent antioxidant capacity (TEAC) (32.28 µmol Trolox/g sample). HPLC analysis showed that the endo-polyphenol production of the crude ethanol extracts was significantly higher than that of the control. Hispidin was isolated and identified from the ethanol extract of the culture mycelia from Ph. baumii with the three-point MA addition strategy. Hispidin showed a strong ability to scavenge DPPH free radicals and TEAC, equivalent to positive (vitamin C) value of 89.41% and 75.98%, respectively. Furthermore, hispidin protected H2O2-induced PC12 cells injured by decreased oxidative stress level. These results indicated that the MA multi-stage addition strategy was dependable, and could be used to develop new natural antioxidants for foods or medicines.


Assuntos
Acetatos/efeitos adversos , Antioxidantes/farmacologia , Basidiomycota/química , Misturas Complexas/farmacologia , Compostos de Magnésio/efeitos adversos , Polifenóis/farmacologia , Pironas/farmacologia , Agaricales , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Cromanos/efeitos adversos , Cromatografia Líquida de Alta Pressão , Misturas Complexas/química , Misturas Complexas/isolamento & purificação , Radicais Livres/efeitos adversos , Peróxido de Hidrogênio/efeitos adversos , Micélio/química , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Polifenóis/química , Polifenóis/isolamento & purificação , Pironas/química , Pironas/isolamento & purificação , Ratos
3.
World Neurosurg ; 138: 201-204, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32179190

RESUMO

BACKGROUND: Hydrogen peroxide (H2O2) solution is commonly used to irrigate wounds because of its hemostatic and antiseptic properties. Previous studies suggest that H2O2 can result in toxicity to keratinocytes and fibroblasts, but complications after H2O2 application, including oxygen embolism, which is one of the most severe, have rarely been reported. CASE DESCRIPTION: A 40-year-old woman was diagnosed with L4-5 lumbar spinal stenosis and subsequently underwent minimally invasive transforaminal lumbar interbody fusion treatment at another hospital. Hypotension, hypoxia, and a decrease in end-tidal carbon dioxide pressure occurred immediately after H2O2 irrigation. After the operation, she was able to be extubated but remained comatose. Postoperative computed tomography scan revealed intracranial air trapping in the right frontal lobe and multiple cerebral infarction foci. CONCLUSIONS: When using a knee-prone surgical position or in cases of dural laceration, the application of undiluted H2O2 solution should be avoided, especially in a surgical wound within a closed cavity. When hypotension, hypoxia, and a decrease in end-tidal carbon dioxide pressure occur immediately after H2O2 irrigation, oxygen embolism should be strongly suspected.


Assuntos
Anti-Infecciosos Locais/efeitos adversos , Embolia Aérea/etiologia , Peróxido de Hidrogênio/efeitos adversos , Pneumocefalia/etiologia , Complicações Pós-Operatórias/etiologia , Fusão Vertebral/efeitos adversos , Adulto , Feminino , Humanos , Vértebras Lombares , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Oxigênio , Estenose Espinal/cirurgia
4.
Am J Case Rep ; 21: e920213, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32161253

RESUMO

BACKGROUND Various factors have been implicated in the pathogenesis of infarction after posterior fossa surgery such as venous air embolism, patient's position (seated or prone), hyperflexion of the neck, excessive spinal cord traction, cervical canal stenosis, and systemic arterial hypotension. The main aim of this case report was to elucidate a case in which hydrogen peroxide was implicated in a major and systemic complication after a neurosurgical procedure. CASE REPORT We describe the case of a 5-year-old female patient who was admitted to our hospital because of a cerebellar hemispheric astrocytoma associated with obstructive hydrocephalus and accompanied by 2 syringomyelic cavities in the cervicothoracic portion of the spinal cord. Immediately after gross total resection of the lesion, impaired mobility of the upper and lower extremities was observed, a finding that was not consistent with intraoperative neurophysiologic monitoring data. Hydrogen peroxide had been judiciously used to irrigate the resection tumor cavity. In the next few postoperative days, the patient suffered from transient diabetes insipidus and hyperpyrexia, indicative of hypothalamic injury. CONCLUSIONS Neurological evaluation of the patient, after stabilization of her medical condition, revealed residual spasticity of upper and lower extremities, rendering her able to mobilize via the aid of wheelchair only. The most possible pathophysiologic explanation of her neurological deterioration, including hypothalamic dysfunction, was analyzed. The role of hydrogen peroxide as a source of free radical formation, and its co-responsibility for vascular platelet aggregation and vasoconstriction was considered, upon case review, the main responsible etiologic factor.


Assuntos
Astrocitoma/cirurgia , Neoplasias Cerebelares/cirurgia , Hidrocefalia/cirurgia , Peróxido de Hidrogênio/efeitos adversos , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias , Quadriplegia/etiologia , Pré-Escolar , Feminino , Humanos , Posicionamento do Paciente , Decúbito Ventral
5.
Biomed Res Int ; 2020: 4897170, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149109

RESUMO

Background: Apelin alleviates oxidative stress which contributes to the development of aging. IVDD is a disease closely correlated to aging and oxidative stress which is known to be harmful to NP cells' matrix synthesis. The purpose of the present study was to investigate the role and underlying mechanism of Apelin in NP cells' matrix degradation under oxidative stress. Methods: First, the mRNA and protein expressions of Apelin were checked by RT-PCR and Western blot in NP from normal and degenerative IVD to explore the relationship between Apelin and IVDD preliminarily. Then, H2O2 was used to mimic oxidative stress of NP cells. After treated with Apelin 13 and CQ, the GAG content was assessed by DMMB and the mRNA/protein expressions of NP matrix macromolecules (Collagen II and Aggrecan) and autophagy-related markers (LC3 and p62) were assessed by RT-PCR/Western blot. Finally, TFEB was knocked down by esiRNA-TFEB transfection and the nucleoprotein expression of TFEB and autophagy-related markers (LC3 and p62) were assessed by Western blot to discuss whether TFEB is involved in Apelin regulating autophagy flux in NP cells under oxidative stress. Results: Our data first confirmed that the mRNA and protein expressions of Apelin were decreased with IVDD. Furthermore, Apelin increased GAG content of NP cells and mRNA/protein expressions of NP matrix macromolecules (Collagen II and Aggrecan) and promoted autophagic flux (LC3II/I increased and p62 decreased) under oxidative stress. Finally, after transfected with esiRNA-TFEB, Apelin cannot promote autophagic flux any more in human degenerative NP cells. Conclusion: Our data indicated that Apelin promotes ECM synthesis by enhancing autophagy flux via TFEB in human degenerative NP cells under oxidative stress. This viewpoint may provide a new therapeutic idea for IVDD.


Assuntos
Apelina/farmacologia , Autofagia/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Núcleo Pulposo/citologia , Estresse Oxidativo/efeitos dos fármacos , Adulto , Células Cultivadas , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio/efeitos adversos , Degeneração do Disco Intervertebral/metabolismo , Masculino
6.
Skin Therapy Lett ; 25(1): 1-4, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32023021

RESUMO

HP40 (Eskata™) is a stabilized, topical solution of 40% hydrogen peroxide (H2O2) packaged in an applicator pen that is US FDA-approved to treat seborrheic keratoses (SKs). By harnessing the oxidative capabilities of H2O2 , 1-2 treatments with HP40 produced a higher rate of clearance of four SKs per patient compared to vehicle in two phase 3 trials. The clearance rate was higher for the face than the trunk and extremities. Similarly, the risks of pigmentary changes and scarring from HP40 were lower for the face than other locations. Further, based on an ex vivo study, HP40 may be less cytotoxic to melanocytes than cryotherapy, but clinical trials comparing these therapies are needed. Limitations of HP40 are its low efficacy and requirement of multiple treatments, which can result in elevated costs. The application can also be time-consuming, though extenders or even staff members can apply it. Therefore, HP40 may be better reserved for the treatment of facial SKs.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Peróxido de Hidrogênio/administração & dosagem , Ceratose Seborreica/tratamento farmacológico , Administração Cutânea , Crioterapia/métodos , Fármacos Dermatológicos/efeitos adversos , Humanos , Peróxido de Hidrogênio/efeitos adversos , Ceratose Seborreica/patologia , Resultado do Tratamento
7.
Food Funct ; 11(2): 1754-1763, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32043502

RESUMO

Carvacryl acetate (CA) is a semisynthetic monoterpenic ester obtained from essential oils, and it exerts an antioxidation effect. The purpose of our study was to investigate whether CA could provide neuroprotection against oxidative stress caused by cerebral ischemia-reperfusion injury (CIRI) and elucidate the underlying mechanism. Middle cerebral artery occlusion (MCAO)-induced damage was established in Sprague Dawley (SD) rats and PC12 cells were exposed to hydrogen peroxide (H2O2) to imitate oxidative stress damage. TTC, HE and Nissl staining were used to observe the pathological morphology of lesions. The contents of ROS and MDA, and the activity of SOD were measured to reflect the level of oxidative stress. In addition, the TUNEL method was used to assess injuries in vitro, and the expression of Nrf2 was determined by immunohistochemical staining and western blot analysis. Importantly, we constructed and validated Nrf2 knockdown PC12 cells to confirm the key role of Nrf2 in the neuroprotective effect of CA against oxidative stress injuries. CA alleviated CIRI in rats with MCAO, as shown by brain tissue pathophysiology. The contents of ROS and MDA were reduced, and the SOD activity was augmented by the simultaneous promotion of Nrf2 expression. In addition, the H2O2-induced injury in Nrf2-knockdown PC12 cells was more serious than it was in control cells, and CA-mediated neuroprotection was exclusively inhibited by the knock down of Nrf2 in PC12 cells. In conclusion, it is shown here that CA has the effect of relieving cerebral ischemia reperfusion-induced oxidative stress injury via the Nrf2 signalling pathway.


Assuntos
Isquemia Encefálica , Monoterpenos/farmacologia , Fármacos Neuroprotetores/farmacologia , Óleos Voláteis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/metabolismo , Peróxido de Hidrogênio/efeitos adversos , Monoterpenos/química , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/química , Óleos Voláteis/química , Células PC12 , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/induzido quimicamente , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos
8.
BMC Musculoskelet Disord ; 21(1): 58, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000742

RESUMO

BACKGROUND: Hydrogen peroxide has been widely used in Orthopaedics including Orthopaedic oncology, trauma and joint surgeries. However, we encountered an oxygen embolism and myoglobinuria after hydrogen peroxide was used to irrigate a septic hip arthroscopically. CASE PRESENTATION: A 61-year-old male patient with right hip septic arthritis underwent an arthroscopic hip washout and debridement. During the operation, the surgeon used 100 ml of 3% hydrogen peroxide to irrigate the joint cavity. Two minutes after irrigation, there was a transient decrease in oxygen saturation, heart rate and blood pressure, with significant subcutaneous emphysema around the wound. Concentrated urine was drained out 8 h after operation which resolved the following day. Post-operatively, the patient was managed in the intensive care unit for a pulmonary embolism and discharged without further complications. CONCLUSION: Medical staff should be aware of the risk of oxygen embolism and be extremely careful when using hydrogen peroxide in patient care. Oxygen embolism following hydrogen peroxide use is rare, however, once encountered, it may bring serious consequences. Therefore, the use of hydrogen peroxide in closed spaces or arthroscopic procedures should be discontinued.


Assuntos
Artrite Infecciosa/cirurgia , Artroscopia/efeitos adversos , Embolia Aérea/etiologia , Peróxido de Hidrogênio/efeitos adversos , Ossos Pélvicos/cirurgia , Irrigação Terapêutica/efeitos adversos , Artrite Infecciosa/diagnóstico por imagem , Artroscopia/métodos , Desbridamento/efeitos adversos , Desbridamento/métodos , Embolia Aérea/diagnóstico por imagem , Humanos , Peróxido de Hidrogênio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oxigênio , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/microbiologia , Irrigação Terapêutica/métodos
9.
Biomater Sci ; 8(6): 1695-1701, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-31989134

RESUMO

Spinal cord injury is one of the most serious traumatic diseases. The current available clinical therapies are unable to provide effective recovery of nerve functions. Implantation of biomaterial scaffolds is a promising approach to bridge the damaged nerve tissue in the absence of the extracellular matrix. However, the treatments have been impaired by the increased generation of reactive oxygen species in the microenvironment of acute spinal cord injury. Efficient delivery of antioxidants and biocompatible materials and reagents has been a challenge. Herein, a novel hyaluronic acid (HA) hydrogel functionalized with the antioxidant compound 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) is fabricated for nerve tissue regeneration after serious spinal cord transection in rats. TEMPO is tethered onto HA chains to form HA-TEMPO through a Schiff base reaction between 4-amino-TEMPO and aldehyde modified HA chains. The TEMPO-hydrogel is constructed with a highly porous three-dimensional structure via the gelation between the residue aldehydes in HA-TEMPO and the amines in adipic dihydrazide modified HA. The functional TEMPO-hydrogel exhibits the antioxidant effect in an H2O2 simulated in vitro peroxidative microenvironment. Implantation of the functional hydrogel in vivo induces a significant motor function restoration, which could be attributed to the effective functions of the TEMPO-hydrogel in tissue reconnection as well as nerve fiber regeneration of the central nervous spinal cord tissue. Importantly, the treatment with the TEMPO-hydrogel effectively protects the bladder tissue from neurogenic damage. Therefore, the functional TEMPO-hydrogel provides a promising strategy for the treatment of central nervous system diseases through the antioxidant and lesion-bridging regulation of the pathological microenvironment.


Assuntos
Antioxidantes/farmacologia , Óxidos N-Cíclicos/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Traumatismos da Medula Espinal/terapia , Bexiga Urinária/efeitos dos fármacos , Animais , Antioxidantes/química , Óxidos N-Cíclicos/química , Modelos Animais de Doenças , Ácido Hialurônico/química , Hidrogéis/química , Peróxido de Hidrogênio/efeitos adversos , Masculino , Ratos , Bases de Schiff/química , Tecidos Suporte/química , Transplante de Tecidos , Resultado do Tratamento
10.
Pharm Nanotechnol ; 8(1): 63-75, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31577213

RESUMO

BACKGROUND: Type 1 diabetes mellitus is characterized by the destruction of insulin- producing Beta cells in the pancreas. Researchers hope that islet transplantation will help to patients with insulin-dependent diabetes mellitus (IDDM). Oxidative stress is the most important challenge that beta cells face to it after isolation, and mitochondrial dysfunction is a crucial mediator in beta cells death. Hence, therapeutic approaches can shift to antioxidants through the application of nanoparticles such as cerium and yttrium oxide nanoparticles (Cer and Ytt Ox NPs) and nano-selenium (Nan Se). OBJECTIVE: This study evaluates the effects of Cer and Ytt Ox NPs and Nan Se on H2O2- induced oxidative stress in pancreatic beta cells with focus on mitochondrial dysfunction pathway. METHODS: CRI-D2 beta-cell line were pretreated with Cer Ox NPs (200 µM) + Ytt Ox NPs (0.5 µg/mL) for 3 days and/or Nan Se (0.01 µM) for 1 day. Then markers of oxidative stress, mitochondrial dysfunction, insulin and glucagon secretion were measured. RESULTS: We reported a decrease in H2O2-induced reactive oxygen species (ROS) level and glucagon secretion, and an increase in H2O2-reduced ATP/ADP ratio, MMP, as well as UCP2 protein expression, and insulin secretion by pretreatment of CRI-D2 cells with Cer and Ytt Ox NPs and/or Nan Se. CONCLUSION: We found maximum protective effect with Cer and Ytt Ox NPs on CRI-D2 beta-cell line exposed by H2O2 for keeping beta cells alive until transplant whereas combination of Cer and Ytt Ox NPs and Nan Se had very little protective effect in this condition.


Assuntos
Antioxidantes/farmacologia , Cério/farmacologia , Peróxido de Hidrogênio/efeitos adversos , Células Secretoras de Insulina/citologia , Selênio/farmacologia , Ítrio/farmacologia , Animais , Antioxidantes/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Cério/química , Glucagon/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Ratos , Selênio/química , Proteína Desacopladora 2/metabolismo , Ítrio/química
11.
J Nat Med ; 74(1): 34-40, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31256310

RESUMO

Four new cucurbitane-type triterpenes were isolated from the fruit of Momordica charantia L. The structures of the new compounds were identified based on HR-ESI-MS and 1D- and 2D-NMR spectroscopic methods. The cytotoxicity of the isolated compounds was evaluated using three human cancer cell lines, HeLa, Caco2, and U87. Compound 3 exhibited significant cytotoxic activity against HeLa cells with an IC50 value of 11.18 µM. Additionally, the cytoprotective activity of these compounds was determined in vitro against H2O2-induced pancreatic injury. The results revealed that all the compounds obtained possess cytoprotective effects against H2O2-induced injury in MIN6 ß-cells at a concentration of 10 µM.


Assuntos
Glicosídeos/química , Peróxido de Hidrogênio/efeitos adversos , Momordica charantia/química , Pâncreas/efeitos dos fármacos , Triterpenos/química , Humanos
12.
J Cosmet Dermatol ; 19(2): 416-422, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31175696

RESUMO

BACKGROUND: Warts are common viral skin infections caused by human papillomavirus. None of the available treatment modalities fulfills the criteria of an ideal treatment option. OBJECTIVES: To evaluate the efficacy and safety of hydrogen peroxide (HP) 3% and 6% solution as a topical treatment of nongenital warts. METHODS: This prospective randomized controlled study included 145 patients with nongenital warts. They were divided into three groups. Group 1 used topical hydrogen peroxide 6% solution under occlusion with a plastic tape for one hour daily for 6 weeks, group 2 used hydrogen peroxide 3% solution, and group 3 used normal saline 0.9% as a placebo. Patients were evaluated at the third and sixth weeks of treatment and 12 weeks after treatment completion. RESULTS: Treatment responses were significantly better in groups 1 and 2 than in group 3 with a better overall responses in group 1 than in group 2 (P = 0.0001*). Apart from mild hypopigmentation which was detected in only two patients in groups 1 and 2, no other side effects could be detected. Three months after treatment completion, no recurrence was observed. CONCLUSION: Hydrogen peroxide solution (3% and 6%) is an effective, safe, and cheap treatment modality for nongenital warts which can be used simply at home. Since the overall response was better with the 6% concentration, it should be the better therapeutic option.


Assuntos
Peróxido de Hidrogênio/administração & dosagem , Oxidantes/administração & dosagem , Verrugas/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Peróxido de Hidrogênio/efeitos adversos , Hipopigmentação/induzido quimicamente , Hipopigmentação/epidemiologia , Masculino , Pessoa de Meia-Idade , Curativos Oclusivos , Oxidantes/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
13.
Mol Cell Endocrinol ; 500: 110631, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31676390

RESUMO

The reduction in muscle mass and strength with age, sarcopenia, is a prevalent condition among the elderly, linked to skeletal muscle dysfunction and cell apoptosis. We demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 muscle cells. Here, we analyzed the effect of testosterone on mitochondrial gene expression in C2C12 skeletal muscle cells. We found that testosterone increases mRNA expression of genes encoded by mitochondrial DNA, such as NADPH dehydrogenase subunit 1 (ND1), subunit 4 (ND4), cytochrome b (CytB), cytochrome c oxidase subunit 1 (Cox1) and subunit 2 (Cox2) in C2C12. Additionally, the hormone induced the expression of the nuclear respiratory factors 1 and 2 (Nrf-1 and Nrf-2), the mitochondrial transcription factors A (Tfam) and B2 (TFB2M), and the optic atrophy 1 (OPA1). The simultaneous treatment with testosterone and the androgen receptor antagonist, Flutamide, reduced these effects. H2O2-oxidative stress induced treatment, significantly decreased mitochondrial gene expression. Computational analysis revealed that mitochondrial DNA contains specific sequences, which the androgen receptor could recognize and bind, probably taking place a direct regulation of mitochondrial transcription by the receptor. These findings indicate that androgen plays an important role in the regulation of mitochondrial transcription and biogenesis in skeletal muscle.


Assuntos
Mitocôndrias/genética , Proteínas Mitocondriais/genética , Fibras Musculares Esqueléticas/citologia , Testosterona/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Flutamida/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/efeitos adversos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Camundongos , Mitocôndrias/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , NADH Desidrogenase/genética , Fator 1 Nuclear Respiratório , Estresse Oxidativo/efeitos dos fármacos , Regulação para Cima
14.
Clin Exp Med ; 20(1): 31-37, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31679095

RESUMO

Raynaud's phenomenon (RP) is a clinical disorder characterized by recurrent, reversible episodes of digital vasospasm. RP can be classified as primary (pRP) or secondary, depending on whether it occurs as a benign condition (not disease-associated) or is associated with other diseases, mainly of the connective tissues. In both cases, it can be triggered by environmental factors, as indicated by the increased incidence of pRP episodes following exposure to cold, vibration injury or chemicals. The purpose of this prospective case-control study was to assess, in an Italian cohort of 132 pRP patients, the association of the phenomenon with demographic, lifestyle habits, environmental and work-related factors. Compared to healthy controls, pRP was found to be inversely associated with the use of contact lenses (OR = 0.4; p = 0.004) and of chlorous-based disinfectants (OR = 0.3; p < 0.001) and directly associated with the presence of prosthesis implants (OR = 5.3; p = 0.001) and the use of hydrogen peroxide-based compounds (OR = 2.6; p = 0.002), suggesting that the latter should be avoided in RP affected patients. Multivariate and multivariable analysis confirmed the associations. Further investigations are needed to understand the mechanism(s) underlying these findings.


Assuntos
Lentes de Contato/estatística & dados numéricos , Peróxido de Hidrogênio/efeitos adversos , Próteses e Implantes/efeitos adversos , Doença de Raynaud/epidemiologia , Adulto , Estudos de Casos e Controles , Desinfetantes/química , Feminino , Humanos , Incidência , Itália/epidemiologia , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Próteses e Implantes/estatística & dados numéricos , Doença de Raynaud/etiologia
15.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31701151

RESUMO

BACKGROUND: The early molecular events in human thyrocytes after 131I exposure have not yet been unravelled. Therefore, we investigated the role of TSH in the 131I-induced DNA damage response and gene expression in primary cultured human thyrocytes. METHODS: Following exposure of thyrocytes, in the presence or absence of TSH, to 131I (ß radiation), γ radiation (3 Gy), and hydrogen peroxide (H2O2), we assessed DNA damage, proliferation, and cell-cycle status. We conducted RNA sequencing to profile gene expression after each type of exposure and evaluated the influence of TSH on each transcriptomic response. RESULTS: Overall, the thyrocyte responses following exposure to ß or γ radiation and to H2O2 were similar. However, TSH increased 131I-induced DNA damage, an effect partially diminished after iodide uptake inhibition. Specifically, TSH increased the number of DNA double-strand breaks in nonexposed thyrocytes and thus predisposed them to greater damage following 131I exposure. This effect most likely occurred via Gα q cascade and a rise in intracellular reactive oxygen species (ROS) levels. ß and γ radiation prolonged thyroid cell-cycle arrest to a similar extent without sign of apoptosis. The gene expression profiles of thyrocytes exposed to ß/γ radiation or H2O2 were overlapping. Modulations in genes involved in inflammatory response, apoptosis, and proliferation were observed. TSH increased the number and intensity of modulation of differentially expressed genes after 131I exposure. CONCLUSIONS: TSH specifically increased 131I-induced DNA damage probably via a rise in ROS levels and produced a more prominent transcriptomic response after exposure to 131I.


Assuntos
Dano ao DNA/fisiologia , Raios gama/efeitos adversos , Peróxido de Hidrogênio/efeitos adversos , Radioisótopos do Iodo/efeitos adversos , Tireotropina/metabolismo , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Cultura Primária de Células , Células Epiteliais da Tireoide/metabolismo
16.
J Microbiol Biotechnol ; 29(12): 1925-1930, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31635447

RESUMO

Carotenoids are organic pigments with antioxidant properties and are widespread in nature. Here, we isolated five microbes, each forming yellow-colored colonies and harboring C30 carotenoid biosynthetic genes (crtM and crtN). Thereafter, Lactobacillus plantarum subsp. plantarum KCCP11226, which showed the highest carotenoid production, was finally selected and the produced pigment was identified as C30 carotenoid 4,4'-diaponeurosporene. This strain exhibited the highest survival rate under oxidative stress and its carotenoid production was also enhanced after exposure to 7 mM H2O2. Moreover, it showed the highest ability to scavenge DPPH free radical. Our results suggested that L. plantarum subsp. plantarum KCCP11226, which produces 4,4'-diaponeurosporene as a natural antioxidant, may be a functional probiotic.


Assuntos
Antioxidantes/metabolismo , Carotenoides/metabolismo , Lactobacillus plantarum/isolamento & purificação , Lactobacillus plantarum/metabolismo , Triterpenos/metabolismo , Genes Bacterianos/genética , Peróxido de Hidrogênio/efeitos adversos , Peróxido de Hidrogênio/farmacologia , Lactobacillus plantarum/genética , Probióticos
17.
J Med Food ; 22(12): 1280-1293, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31584314

RESUMO

Opuntia ficus indica has been an important dietary source and a traditionally used medicinal plant. Given the promising health-promoting properties of this plant, a comparative toxicological assessment and antioxidant bioevaluation of extracts from different parts of the plant were carried out in relation to their chemical profile. Toxicity was examined at multiple endpoints using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), Comet and the γH2AX In-Cell Western Assay, while hyphenated ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analysis was carried out to identify main constituents. None of the extracts showed any cytotoxic and genotoxic effect on cell lines used, apart from the flower extract in HepG2 cells at the highest concentration tested (2.5 mg/mL). Both fruit flesh and seed extracts demonstrated a prominent protective effect against H2O2-induced genotoxicity in almost all concentrations tested, while extracts originated from flowers and cladodes were effective only at the low non-cytotoxic (0.312 and 0.625 mg/mL) and high (1.25 and 2.5 mg/mL) concentrations, respectively. In total, 2 phenolic acids, 12 flavonoids, along with 3 feruloyl derivatives and the plant pigment indicaxanthin, were tentatively identified by UHPLC-HRMS analysis. Phenolic acids (compounds 1 and 2) were mainly distributed in cladodes (64.6%), while flavonoids (3-14) in the flowers (81.8%). Overall, the highest amount of total flavonoids (22.76 ± 0.015 mg of quercetin equivalent [QE]/g) and total phenolics (62.80 ± 0.009 mg gallic acid equivalents [GAE]/g) was found in the flower extract. Flavonoid glycosides have not been detected in the seeds and the flesh, while the fruit seed extract contained mainly feruloyl derivatives. Our data provide convincing evidences for the lack of cytotoxic and genotoxic effects of O. ficus indica aqueous extracts and, in parallel, support the potential for further exploitation of this plant in the food supplement or functional food sector.


Assuntos
Cromatografia Líquida de Alta Pressão , Dano ao DNA/efeitos dos fármacos , Peróxido de Hidrogênio/efeitos adversos , Opuntia/química , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Betaxantinas/análise , Flavonoides/análise , Flores/anatomia & histologia , Frutas/química , Células HeLa , Células Hep G2 , Humanos , Hidroxibenzoatos/análise , Espectrometria de Massas , Testes de Mutagenicidade , Fenóis/análise , Extratos Vegetais/química , Piridinas/análise , Quercetina/análise , Sementes/química
18.
Oxid Med Cell Longev ; 2019: 8098135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583045

RESUMO

The oxidative stress of vessel endothelium is a major risk factor of cardiovascular disorders. Antioxidative stress drugs are widely used in cardiovascular therapy. Aspirin eugenol ester (AEE) is a new pharmaceutical compound synthesized by esterification reaction of aspirin with eugenols and possesses antioxidative activity. The present study was designed to investigate the mechanism how AEE protects human umbilical vein endothelial cells (HUVECs) from H2O2-induced oxidative stress. H2O2 was given to the HUVECs with or without AEE pretreatment. Changes in the oxidative stress-related factors, including those related to the mitochondria-lysosome axis, were determined with Western blotting, cellular immunofluorescence, and enzyme activity test. The results showed that, in the HUVECs, 300 µM H2O2 treatment significantly increased the apoptosis rate, MDA concentration, reactive oxygen species (ROS) production, mitochondrial membrane potential, expression of Bax and mature cathepsin D (CTSD), and activity of CTSD and Caspase3 (Cas3) but decreased the expression of Bcl2 and lysosomal membrane stability, while in the HUVECs pretreated with AEE, the above changes caused by either the stimulatory or the inhibitory effect of H2O2 on the relevant factors were significantly reduced. AEE pretreatment significantly enhanced the activity of cellular superoxide dismutase and glutathione peroxidase in the HUVECs. Our findings suggest that AEE effectively reduced H2O2-induced oxidative stress in the HUVECs via mitochondria-lysosome axis.


Assuntos
Aspirina/análogos & derivados , Eugenol/análogos & derivados , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Peróxido de Hidrogênio/efeitos adversos , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Aspirina/farmacologia , Aspirina/uso terapêutico , Eugenol/farmacologia , Eugenol/uso terapêutico , Humanos
19.
Int J Mol Sci ; 20(18)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540288

RESUMO

Human mesenchymal stem cells (hMSCs) are a potent source of cell-based regenerative therapeutics used to treat patients with ischemic disease. However, disease-induced oxidative stress disrupts mitochondrial homeostasis in transplanted hMSCs, resulting in hMSC apoptosis and reducing their efficacy post-transplantation. To address this issue, we evaluated the effects of melatonin on cellular defense mechanisms and mitophagy in hMSCs subjected to oxidative stress. H2O2-induced oxidative stress increases the levels of reactive oxygen species and reduces membrane potential in hMSCs, leading to mitochondrial dysfunction and cell death. Oxidative stress also decreases the expression of 70-kDa heat shock protein 1L (HSPA1L), a molecular chaperone that assists in the recruitment of parkin to the autophagosomal mitochondrial membrane. Decreased expression of HSPA1L destabilizes parkin, thereby impairing mitophagy. Our results indicate that treating hMSCs with melatonin significantly inhibited mitochondrial dysfunction induced by oxidative stress, which decreased hMSCs apoptosis. In damaged hMSCs, treatment with melatonin increased the levels of HSPA1L, which bound to parkin. The interaction between HSPA1L and parkin increased membrane potential and levels of oxidative phosphorylation, resulting in enhanced mitophagy. Our results indicate that melatonin increased the expression of HSPA1L, thereby upregulating mitophagy and prolonging cell survival under conditions of oxidative stress. In this study, we have shown that melatonin, a readily available compound, can be used to improve hMSC-based therapies for patients with pathologic conditions involving oxidative stress.


Assuntos
Proteínas de Choque Térmico HSP70/genética , Melatonina/farmacologia , Células-Tronco Mesenquimais/citologia , Mitofagia/efeitos dos fármacos , Regulação para Cima , Células Cultivadas , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Peróxido de Hidrogênio/efeitos adversos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Estresse Oxidativo , Estabilidade Proteica , Espécies Reativas de Oxigênio/metabolismo , Ativação Transcricional , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo
20.
Proc Natl Acad Sci U S A ; 116(36): 17980-17989, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31434789

RESUMO

The fat mass and obesity-associated gene (FTO) encodes an m6A RNA demethylase that controls mRNA processing and has been linked to both obesity and bone mineral density in humans by genome-wide association studies. To examine the role of FTO in bone, we characterized the phenotype of mice lacking Fto globally (Fto KO ) or selectively in osteoblasts (Fto Oc KO ). Both mouse models developed age-related reductions in bone volume in both the trabecular and cortical compartments. RNA profiling in osteoblasts following acute disruption of Fto revealed changes in transcripts of Hspa1a and other genes in the DNA repair pathway containing consensus m6A motifs required for demethylation by Fto Fto KO osteoblasts were more susceptible to genotoxic agents (UV and H2O2) and exhibited increased rates of apoptosis. Importantly, forced expression of Hspa1a or inhibition of NF-κB signaling normalized the DNA damage and apoptotic rates in Fto KO osteoblasts. Furthermore, increased metabolic stress induced in mice by feeding a high-fat diet induced greater DNA damage in osteoblast of Fto Oc KO mice compared to controls. These data suggest that FTO functions intrinsically in osteoblasts through Hspa1a-NF-κB signaling to enhance the stability of mRNA of proteins that function to protect cells from genotoxic damage.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Apoptose , Osso e Ossos/metabolismo , Dano ao DNA , Osteoblastos/metabolismo , Transdução de Sinais , Estresse Fisiológico , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Animais , Osso e Ossos/patologia , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Peróxido de Hidrogênio/efeitos adversos , Peróxido de Hidrogênio/farmacologia , Camundongos , Camundongos Knockout , NF-kappa B/genética , NF-kappa B/metabolismo , Osteoblastos/patologia , Raios Ultravioleta/efeitos adversos
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