Pharmacotherapeutic potential of Vitis vinifera(grape) in age-related neurological diseases / Potencial farmacoterapéutico de Vitis vinifera(uva) en enfermedades neurológicas asociadas a la edad

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are complex illnesses with an increasing risk with advancing years. The central nervous system's neuropathological conditions, including oxidative stress, neuroinflammation, and protein misfolding, are what define ANDs. Due to the rise in age-dependent prevalence, efforts have been made to combat ANDs. Vitis viniferahas a long history of usageto treat a variety of illness symptoms. Because multiple ligand sites may be targeted, Vitis viniferacomponents can be employed to treat ANDs. This is demonstrated by the link between the structure and action of these compounds. This review demonstrates that Vitis viniferaand its constituents, including flavonoids, phenolic compounds, stilbenoidsandaromatic acids, are effective at reducing the neurological symptoms and pathological conditions of ANDs. This is done by acting as an antioxidant and anti-inflammatory. The active Vitis vinifera ingredients have therapeutic effects on ANDs, as this review explains.

Las enfermedades neurológicas asociadas a la edad (AND, por su sigla en inglés) incluyendo las enfermedades neurodegenerativas, son enfermedades complejas con un riesgo creciente con la edad. Las condiciones neuropatológicas del sistema nervioso central, que incluyen el estrés oxidativo, la neuro inflamación, y el plegado erróneo de proteínas, son lo que define las AND. Debido al aumento en la prevalencia dependiente de la edad, se han hecho esfuerzos para combatir las AND. Vitis vinifera tiene una larga historia de uso para el tratamiento de síntomas. Puesto que puede hacer objetivo a muchos sitios ligando, los componentes de Vitis viniferase pueden utilizar para tratar AND. Esto se demuestra por el vínculo entre la estructura y la acción de estos compuestos. Esta revisión demuestra que la Vitis viniferay sus constituyentes, incluídos los flavonoides, componentes fenólicos, estilbenoides, y ácidos aromáticos, son efectivos para reducir los síntomas neurológicos y las condiciones patológicas de AND. Esto se produce por su acción como antioxidante y antiinflamatorio. Los ingredientes activos de Vitis vinifera tienen efectos terapéuticos en AND, y esta revisión lo explica.

Otimização de método extrativo para raízes de Arctium lappa L / Extractive method optimization for Arctium lappa l. Roots / Optimización de un método de extracción de raíces de Arctium lappa L

Arctium lappa L. é indicada no Formulário de Fitoterápicos da Farmacopeia Brasileira para o tratamento de distúrbios urinários leves. Estudos já demonstraram o potencial antioxidante, anti-inflamatório e antidiabético deste extrato, onde foram identificados fenóis, lignanas, taninos e flavonoides. O objetivo deste trabalho foi otimizar o método extrativo de raízes de A. lappa. Realizou-se o preparo de extratos por diferentes métodos: Ultrassom, Soxhlet, maceração e turbo extração. A otimização foi realizada por turbo extração seguindo um planejamento fatorial 23, empregando como fatores: teor alcoólico, concentração da matéria prima e tempo de extração. Os extratos foram avaliados quanto ao resíduo seco, teores de fenóis e flavonoides, e atividade antioxidante. Com relação ao resíduo seco, e aos teores de fenóis e flavonoides, os métodos de ultrassom e turbo extração demonstraram melhor poder extrativo. Devido ao menor tempo e custo operacional, a otimização foi realizada por turbo extração, e o extrato otimizado foi obtido utilizando álcool 60%, em proporção matéria prima solvente 1:10 e tempo de extração de 15 minutos. Estas análises poderão nortear futuros testes de transposição de método para escala industrial, diminuindo mão de obra, tempo e custos, visando obter produtos fitoterápicos mais eficientes, com valor acessível à população.

Arctium lappa L. is indicated in the Brazilian Pharmacopeia Herbal Medicines Form for the treatment of mild urinary disorders. Studies have already demonstrated the antioxidant, anti-inflammatory and antidiabetic potential of this extract, where phenols, lignans, tannins and flavonoids were identified. The objective of this work was to optimize the extractive method of A. lappa roots. Extracts were prepared by different methods: Ultrasound, Soxhlet, maceration and vortical extraction. The optimization was performed by vortical extraction following a 23 full factorial design, using as factors: alcohol content, drug concentration and extraction time. The extracts were evaluated for dry residue, phenols and flavonoids contents, and antioxidant activity. Regarding the dry residue, and the phenols and flavonoids contents, the ultrasound and vortical extraction methods showed better extractive power. Due to the lower operating time and cost, the optimization was performed by vortical extraction, and the optimized extract was obtained using 60% alcohol, in a 1:10 drug solvent ratio and extraction time of 15 minutes. These assessments guide the future tests of transposition of the method to an industrial scale, reducing manpower, time and costs, aiming to obtain more efficient phytotherapic products, with affordable value for the population.

Arctium lappa L. está indicado en la Formulacao de Fitoterápicos da Farmacopeia Brasileira para el tratamiento de trastornos urinarios leves. Los estudios han demostrado el potencial antioxidante, antiinflamatorio y antidiabético de este extracto, donde se identificaron fenoles, lignanos, taninos y flavonoides. El objetivo de este trabajo fue optimizar el método extractivo de las raíces de A. lappa. Los extractos se prepararon por diferentes métodos: Ultrasonido, Soxhlet, maceración y turboextracción. La optimización se realizó mediante turboextracción siguiendo una planificación factorial de 23, empleando como factores: tenor alcohólico, concentración de materia prima y tiempo de extracción. Se evaluaron los extractos para determinar el residuo seco, el contenido de fenoles y flavonoides y la actividad antioxidante. En cuanto al contenido de residuo seco, fenoles y flavonoides, los métodos de extracción por ultrasonidos y turbo demostraron un mejor poder de extracción. Debido al menor tiempo y coste operativo, la optimización se realizó mediante turboextracción, y el extracto optimizado se obtuvo utilizando alcohol 60%, en proporción disolvente-materia 1:10 y tiempo de extracción de 15 minutos. Estos análisis podrán orientar futuros ensayos de transposición del método para escala industrial, reduciendo mano de obra, tiempo y costes, con el objetivo de obtener productos fitoterapéuticos más eficientes, con valor accesible para la población.

Radioprotective Effect of Nigella Sativa Oil on Heart Tissues of Rats Exposed to Irradition

Abstract Background Various studies are ongoing related to the radioprotective agents. Herbal preparations are currently becoming popular because of their beneficial effects with fewer side effects compared to the synthetic/semi-synthetic medicines, and Nigella sativa oil (NSO) is only one of them. Objective To investigate NSO for its antioxidant effects on the heart tissue of rats exposed to ionizing radiation (IR). Methods Thirty six male albino Wistar rats, divided into four groups, were designated to group I (IR plus NSO group) that received both 5 Gray of gamma IR to total cranium and NSO; group II (IR alone group) that received IR plus saline, group III (control group of NSO) that received saline and did not receive NSO or IR; group IV (control group) that received only sham IR. Alterations in Total antioxidant status (TAS) and Total oxidant status (TOS), Oxidative stres index (OSI), Sulhydryl group (SH), Lipid hydroperoxide (LOOH), Paraoxonase (PON) levels, Arylesterase (ARE) and Ceruloplasmin (CER) activities in homogenized heart tissue of rats were measured by biochemical methods. Results In heart tissue of the rats in the IR alone group (group II) LOOH, TOS and OSI levels were found to be higher, ARE activity and TAS level were found to be lower than all of the other groups (p < 0.01). These results also support that IR increases oxidative stress and NSO's protective effect. Conclusion NSO would reduce the oxidative damage in the irradiated heart tissue in the experimental rat model.

Effects of artichoke leaf extract on hepatic ischemia-reperfusion injury

SUMMARY OBJECTIVE: The aim of this study was to evaluate the hepatoprotective effect and mechanism of action of artichoke leaf extract in hepatic ischemia/reperfusion injury. METHODS: Rats were divided into three groups such as sham, control, and artichoke leaf extract groups. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum obtained from the subjects. Histopathological findings were scored semiquantitatively. RESULTS: Statistically, the antioxidant activity was highest in the artichoke leaf extract group, the difference in biochemical parameters and C-reactive protein was significant compared with the control group, and the histopathological positive effects were found to be significantly higher. CONCLUSIONS: As a result, artichoke leaf extract had a hepatoprotective effect and that this effect was related to the antioxidant and anti-inflammatory effects of artichoke.

The combined effect of lifestyle intervention and antioxidant therapy on sperm DNA fragmentation and seminal oxidative stress in IVF patients: a pilot study

ABSTRACT Purpose: Sperm DNA fragmentation (SDF) and seminal oxidative stress are emerging measurable factors in male factor infertility, which interventions could potentially reduce. We evaluated (i) the impact of lifestyle changes combined with oral antioxidant intake on sperm DNA fragmentation index (DFI) and static oxidation-reduction potential (sORP), and (ii) the correlation between DFI and sORP. Materials and Methods: We conducted a prospective study involving 93 infertile males with a history of failed IVF/ICSI. Ten healthy male volunteers served as controls. Semen analysis was carried out according to 2010 WHO manual, whereas seminal sORP was measured using the MiOXSYS platform. SDF was assessed by sperm chromatin structure assay. Participants with DFI >15% underwent a three-month lifestyle intervention program, primarily based on diet and exercise, combined with oral antioxidant therapy using multivitamins, coenzyme Q10, omega-3, and oligo-elements. We assessed changes in semen parameters, DFI, and sORP, and compared DFI results to those of volunteers obtained two weeks apart. Spearman rank correlation tests were computed for sORP and DFI results. Results: Thirty-eight (40.8%) patients had DFI >15%, of whom 31 participated in the intervention program. A significant decrease in median DFI from 25.8% to 18.0% was seen after the intervention (P <0.0001). The mean DFI decrease was 7.2% (95% CI: 4.8-9.5%; P <0.0001), whereas it was 0.42% (95%CI; -4.8 to 5.6%) in volunteers (P <0.00001). No differences were observed in sperm parameters and sORP. Based on paired sORP and DFI data from 86 patients, no correlation was observed between sORP and DFI values (rho=0.03). Conclusion: A 3-month lifestyle intervention program combined with antioxidant therapy reduced DFI in infertile men with elevated SDF and a history of failed IVF/ICSI. A personalized lifestyle and antioxidant intervention could improve fertility of subfertile couples through a reduction in DFI, albeit controlled trials evaluating reproductive outcomes are needed before firm conclusions can be made. Trial registration number and date: clinicaltrials.gov NCT03898752, April 2, 2019.

Estrés oxidativo en saliva generado por el humo de tabaco: impacto en la periodontitis y perspectivas hacia el uso de farmacología redox / Oxidative stress in saliva induced by tobacco smoke: impact on periodontitis and perspectives with redox pharmacology / Estresse oxidativo na saliva gerado pela fumaça do tabaco: impacto na periodontite e perspectivas para o uso da farmacologia redox

Numerosos reportes demuestran la presencia de biomarcadores de estrés oxidativo en la saliva de fumadores y hay un creciente interés en correlacionar estos procesos moleculares con la etiología de algunas enfermedades orales, como la periodontitis, una enfermedad inmunoinflamatoria crónica relacionada con un desequilibrio de la homeostasis redox celular. Objetivo: realizar una revisión narrativa sobre la relación entre la disminución de la capacidad antioxidante salival inducida por humo de tabaco, la periodontitis y el potencial uso de farmacología redox para el tratamiento de esta patología. Métodos: se realizó una búsqueda bibliográfica en bases de datos como PUBMED (NLM, NIH, NCBI) y SciELO. Resultados: existe evidencia que relaciona la baja capacidad antioxidante salival con un retraso en el restablecimiento de las condiciones normales en la cavidad oral ante el desarrollo de periodontitis. A su vez, el estado inflamatorio asociado colabora sinérgicamente, provocando un mayor daño tisular con pérdida de tejidos de soporte dentario, fenómeno que podría ser modulado por la acción de farmacología redox. Conclusiones: la intervención con farmacología redox, podría atenuar los biomarcadores de progresión de la enfermedad periodontal, constituyendo una herramienta prometedora para utilizar en conjunto con las estrategias de tratamiento tradicionales.

Numerous reports demonstrate the presence of oxidative stress biomarkers in the saliva of smokers and there is a growing interest in correlating these molecular processes with the etiology of some oral diseases, such as periodontitis, a chronic immunoinlammatory disease related to an imbalance of cellular redox homeostasis. Aims: achieve a narrative review on the relationship between the decrease in salivary antioxidant capacity induced by tobacco smoke, periodontitis, and the potential use of redox pharmacology for the treatment of this pathology. Methods: a bibliographic search was carried out in databases such as PUBMED (NLM, NIH, NCBI) and SciELO. Results: there is evidence that relates the low salivary antioxidant capacity with a delay in the reestablishment of normal conditions in the oral cavity before the development of periodontitis. In turn, the associated inflammatory state collaborates synergistically, causing greater tissue damage with loss of dental support tissues, a phenomenon that could be modulated by the action of redox pharmacology. Conclusions: intervention with redox pharmacology could attenuate the biomarkers of periodontal disease progression, constituting a promising tool to be used in conjunction with traditional treatment strategies.

Muitos artigos demonstram a presença de biomarcadores de estresse oxidativo na saliva de fumantes e há um interesse crescente em correlacionar esses processos moleculares com a etiologia de algumas doenças bucais, como a periodontite, uma doença imunoinlamatória crônica relacionada a um desequilíbrio da redox celular homeostase. Objetivo: realizar uma revisão narrativa sobre a relaçã o entre a diminuiçã o da capacidade antioxidante salivar induzida pela fumaça do tabaco, periodontite e o uso potencial da farmacologia redox para o tratamento desta patologia. Métodos: uma pesquisa bibliográica foi realizada usando bases de dados como PUBMED (NLM, NIH, NCBI) e SciELO. Resultados: há evidências que relacionam a baixa capacidade antioxidante salivar com o retardo no restabelecimento das condições normais da cavidade oral antes do desenvolvimento da periodontite. Por sua vez, o estado inflamatório associado colabora sinergicamente, causando maior dano tecidual com perda de tecidos de suporte dentário, fenômeno que poderia ser modulado pela açã o da farmacologia redox. Conclusões: a intervençã o com a farmacologia redox poderia atenuar os biomarcadores de progressã o da doença periodontal, constituindo-se em uma ferramenta promissora para ser utilizada em conjunto com estratégias tradicionais de tratamento.

Estratégias terapêuticas e atualizações no tratamento de vitiligo / Therapeutic strategies and updates for treatment of vitiligo

O vitiligo é uma desordem dermatológica complexa, cuja patogênese ainda não é totalmente esclarecida. Apesar de não apresentar complicações funcionais no organismo dos pacientes acometidos, o vitiligo pode resultar em um grande impacto psicossocial. Desse modo, é importante que os médicos saibam como conduzir o tratamento dessa patologia. O objetivo deste estudo foi documentar as terapias disponíveis para o tratamento do vitiligo, assim como apontar pesquisas que relataram a utilização dessas opções terapêuticas e os dados resultantes. As terapias abordadas foram corticoides tópicos e sistêmicos, fototerapia e fotoquimioterapias, antioxidantes, imunomoduladores, fenilalanina, despigmentação, procedimentos cirúrgicos e novas abordagens. A monoterapia parece ser menos eficaz no tratamento do vitiligo. A associação de medicação tópica e/ou sistêmica com o uso da fototerapia ultravioleta B de banda estreita parece ser o padrão-ouro para a repigmentação da pele dos pacientes. Medicamentos novos estão em estudo, porém sua eficácia e o estudo dos possíveis efeitos colaterais, principalmente a longo prazo, têm que ser melhores investigados. É necessário que o médico dermatologista, em conjunto com o paciente, escolha a melhor terapia dentre as disponíveis, de acordo com critérios clínicos e a possibilidade de acesso ao tratamento pelo portador. O acompanhamento e a abordagem por uma equipe multiprofissional também são importantes. (AU)

Vitiligo is a complex dermatological disorder, whose pathogenesis has not yet been fully elucidated. Although it does not present functional complications in the affected patients' body, vitiligo can result in a great psychosocial impact. Therefore, it is important that physicians know how to conduct its treatment. This study aimed at documenting the available therapies for the treatment of vitiligo, as well as pointing out studies reporting the use of these therapeutic options and their resulting data. The therapies addressed were topical and systemic corticosteroids, phototherapy, and photochemotherapies, antioxidants, immunomodulators, phenylalanine, depigmentation, surgical procedures, and new approaches. Monotherapy appears to be less effective in the treatment of vitiligo. The combination of topical and/or systemic medication with the use of narrowband ultraviolet B phototherapy seems to be the gold standard for the patients' skin repigmentation. New drugs are under study, but their effectiveness and study of possible side effects, especially in the long run, have to be better investigated. It is necessary that the dermatologist, together with the patient, choose the best therapy among those available, according to clinical criteria and the possibility of access to treatment by the patient. Monitoring and approach by a multiprofessional team is also important. (AU)

Alleviation of diabetes-induced hepatotoxicity by date palm hydroalcoholic extract in rat model; a biochemical, immunohistochemical and stereological study / Alivio de la hepatotoxicidad inducida por diabetes mediante el extracto hidroalcohólico de palmera datilera en modelo de rata: un estudio bioquímico, inmunohistoquímico y estereológico

SUMMARY: The present study was aimed to investigate the hepatoprotective effects of date palm hydroalcoholic extract (DP)in diabetic rats using biochemical and histopathological approaches. Diabetes was induced by administration of 60 mg/kg of streptozotocin intraperitoneally. In this analysis 32 adult rats were randomly divided into four groups; group 1: non-diabetic control whic received 0.1 mL normal saline, group 2:served as non-diabetic control which treated with 270 mg/kg of DP, group 3: served as untreated diabetic, and group 4: diabetic rats treated with 270 mg/kg of DP. Diabetic rats treated with the DP extracts exhibited lower hepatic oxidative stress and lower hepatic enzymes level. Extract treatment decreased the level of malondealdehyde (MDA) as a marker of lipid peroxidation. Stereological estimations revealed a significant increase in the liver volume in diabetic rats which was reduced in DP-treated rats. Immunofluorescence staining showed high synthesis of acrolein as a byproduct of lipid proxidation. While, optical density measurement revealed significant decrease in acrolein after DP administration. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and necrotic nuclei, whereas, DP treatment attenuated the adverse effects of diabetes on the liver represented by relatively healthy hepatocytes and sinusoids. The obtained results indicated that date pam extract was beneficial in the prevention of diabetes-induced hepatotoxicity due to its natural antioxidant constituents. Further preclinical and clinical studies are needed for considering this plant in management of prediabetes and diabetes hepatic complications.

RESUMEN: El presente estudio tuvo como objetivo investigar los efectos hepatoprotectores del extracto hidroalcohólico (DP) de la palmera datilera en ratas diabéticas utilizando enfoques bioquímicos e histopatológicos. La diabetes fue inducida mediante la administración de 60 mg / kg de estreptozotocina por vía intraperitoneal. Se dividieron al azar 32 ratas adultas en cuatro grupos; grupo 1: control no diabético que recibió 0,1 mL de solución salina normal, grupo 2: control no diabético tratado con 270 mg / kg de DP, grupo 3: fue separado como diabético no tratado, y grupo 4: ratas diabéticas tratadas con 270 mg / kg de DP mg / kg de DP. Las ratas diabéticas tratadas con los extractos de DP mostraron menor estrés oxidativo hepático y menor nivel de enzimas hepáticas. El tratamiento con extracto disminuyó el nivel de malondealdehído (MDA) como marcador de la proxidación de lípidos. Las estimaciones estereológicas revelaron un aumento significativo en el volumen del hígado en ratas diabéticas que se redujo en las ratas tratadas con DP. La tinción por inmunofluorescencia mostró una alta síntesis de acroleína como subproducto de la proxidación de lípidos. Mientras que, la medición de la densidad óptica reveló una disminución significativa de la acroleína después de la administración de DP. El examen histopatológico mostró cambios significativos en el tejido hepático diabético no tratado manifestados por vena porta dilatada, infiltración leucocítica, degeneración grasa y núcleos necróticos, mientras que el tratamiento con DP atenuó los efectos adversos de la diabetes en el hígado representados por hepatocitos y sinusoides relativamente sanos. Los resultados obtenidos indicaron que el extracto de palmera datilera fue beneficioso en la prevención de la hepatotoxicidad inducida por diabetes debido a sus constituyentes antioxidantes naturales. Se necesitan más estudios clínicos para considerar esta planta en el manejo de la prediabetes y las complicaciones hepáticas de la diabetes.

Thymoquinone ameliorates acute kidney injury induced by renal ischemia-reperfusion / La timoquinona mejora la lesión renal aguda inducida por isquemia-reperfusión renal

SUMMARY: Renal ischemia-reperfusion injury (IRI)is an unavoidable consequence in renal transplantation and multiple clinical settings. A debate has been raised about the particular role of hypoxia-inducible factor (HF-1α) in the renal injury pathogenesis and the renal cortex ultrastructural alterations. Also, we investigated the antioxidant/anti-inflammatory effect of thymoquinone and its modulatory role on HIF-1α in protection against renal IRI.Adult male Wister albino rats were assigned into 3 groups (n=16); 1) Sham-operated, 2) IRI model and 3) renal IRI pre-treated with thymoquinone 10 mg.kg-1.day-1 (TQ-IRI) for 10 days and at the reperfusion onset. Following the operation, 8 rats from each group were euthanized after 3 hours and the remaining 8 rats at 24 hours. Renal injury was assessed by the increased blood urea nitrogen, creatinine level, and the EGTI histological injury scoreat both 3 and 24h. HIF-1α was upregulated (p<0.01) and was correlated with renal tissue reactive oxygen species (ROS) production and total oxidant capacity (TAC) consumption. Elevated inflammatory markers (NFkB, MCP-1 and VCAM-1) were associated with renal IRI.Thymoquinone treatment inhibited the accumulation of HIF-1α (p<0.01), reduced renal oxidation/inflammation process and markedly diminished renal injury.

RESUMEN: La lesión por isquemia-reperfusión renal (IRR) es una consecuencia inevitable en el trasplante renal como también en múltiples contextos clínicos. Se ha suscitado una discusión referente a la relación particular del factor inducible por hipoxia (HF- 1α) en la patogénesis de la lesión renal y las alteraciones ultraestructurales de la corteza renal. Además, investigamos el efecto antioxidante / antiinflamatorio de la timoquinona y su papel modulador sobre HIF-1α en la protección contra IRR. Se utilizaron ratas albinas Wister macho adultas divididas en 3 grupos (n = 16); 1) Intervención simulada, 2) modelo IRR y 3) IRR pretratado con timoquinona 10 mg/kg-1. día-1 (TQ-IRR) durante 10 días y al inicio de la reperfusión. Posterior a la operación, 8 ratas de cada grupo fueron sacrificadas después de 3 horas y las 8 ratas restantes a las 24 horas. La lesión renal se evaluó por el aumento de nitrógeno ureico en sangre, el nivel de creatinina y la puntuación de lesión histológica EGTI tanto a las 3 como a las 24 horas. HIF-1α se incrementó (p <0,01) y se correlacionó con la producción de especies de oxígeno reactivo (ROS) del tejido renal y el consumo de capacidad oxidante total. Los marcadores inflamatorios elevados (NFkB, MCP-1 y VCAM-1) se asociaron con IRR. El tratamiento con timoquinona inhibió la acumulación de HIF-1α (p <0,01), redujo el proceso de oxidación / inflamación renal y disminuyó notablemente la lesión renal.

Glutathione and IGF-1 in bovine seminal cryopreservation: oxidative stress response and pregnancy rate / [Glutationa e IGF-1 na criopreservação seminal bovina: resposta do estresse oxidativo e taxa de gestação]

The objective of this study was to evaluate the rate of conception, metabolic, and structural conditions of cryopreserved bovine sperm cells, plus extender with IGF-1 and glutathione (GSH). 12 ejaculations of Nelore bulls were used, submitted to treatments: control, gSH (2mM/mL), IGF-1 (100ng/mL) and gSH (1mM/mL) + IGF-1 (50ng/mL). After cryopreservation and thawing the semen passed the fast thermo resistance test (TTR), plasma membrane and acrosomal integrity (PIAI), mitochondrial membrane potential (AP), oxidative stress, and conception rate. Tukey test was used for the statistical analysis of the parametric variables and the Friedman test for nonparametric. The gestation percentage was compared by the Chi-square test. There was no statistical difference (P<0.05) between treatments for the TTRr variable. Otherwise in the oxidative stress evaluated with the CellROX probe was noted that the IGF-1 showed the highest number of reactive cells (P<0.05). The PIAI, AP and gestation rate showed no difference among treatments (P>0.05), with an average of conceptions of 36.58%. It is concluded that IGF-1, gSH and their association did not cause changes in sperm motility, mitochondrial potential, plasma and acrosomal membrane integrity. IGF-1 increased oxidative stress, however, there was no difference in the gestation rate among the treatments.(AU)

Objetivou-se avaliar a taxa de concepção, as condições metabólicas e estrutural das células espermáticas bovinas criopreservadas, acrescidas de diluidores com fator de crescimento semelhante à insulina do tipo 1(IGF-1) e glutationa (GSH). Foram utilizados 12 ejaculados de touros da raça Nelore, submetidos aos tratamentos: controle, gSH (2mM/mL), IGF-1 (100ng/mL) e gSH (1mM/mL) + IGF-1 (50ng/mL). Após a criopreservação e descongelação, o sêmen passou pelos testes de termorresistência rápida (TTRr), integridade de membrana plasmática e acrossomal (PIAI), alto potencial mitocondrial (AP), estresse oxidativo e taxa de concepção. Utilizou-se o teste de Tukey para as análises estatísticas das variáveis paramétricas e o teste de Friedman para as não paramétricas, com significância de 5%. A percentagem de gestação foi comparada pelo teste do qui-quadrado. Não hove diferença estatística (P<0,05) entre os tratamentos para a variável TTRr. Já no estresse oxidativo avaliado com a sonda CellROX, observou-se que o IGF-1 apresentou maior quantidade de células reativas (P<0,05), 36,38± 24,10. A PIAI, o AP e a taxa de gestação não apresentaram diferença entre tratamentos (P>0,05), com média de concepções de 36,58%. Conclui-se que o IGF-1, a gSH e a sua associação não causaram mudanças na motilidade espermática, no potencial mitocondrial, na integridade da membrana plasmática e acrossomal. O IGF-1 aumentou o estresse oxidativo, porém sem diferença na taxa de gestação entre os tratamentos.(AU)

Oxidative stress in leukemia and antioxidant treatment / 中华医学杂志(英文版)

Oxidative stress is caused by the imbalance between the generation of free radicals/reactive oxygen species (ROS) and the antioxidant defense systems, which can activate various transcription factors and affect their transcriptional pathways. Oxidative stress plays an important role in the occurrence and development of leukemia and is closely related to the treatment and prognosis of leukemia. The standard chemotherapy strategies for the pre-treatment of leukemia have many drawbacks. Hence, the usage of antioxidants and oxidants in the treatment of leukemia is being explored and has been preliminarily applied. This article reviews the research progress of oxidative stress and leukemia. In addition, the application of antioxidants treatment in leukemia has been summarized.

Estratificação para predizer a resposta ao tratamento antioxidante em terapia intensiva: um estudo translacional / Stratification to predict the response to antioxidant

RESUMO Objetivo: Avaliar a efetividade da estratificação para identificar e escolher alvos para terapia antioxidante em um modelo de sepse letal em animais e pacientes que desenvolveram hipotensão prolongada. Métodos: Submeteu-se um grupo de ratos à sepse induzida por ligadura e punção do ceco. Os animais foram divididos em dois grupos: os com níveis plasmáticos altos e os com níveis plasmáticos baixos de interleucina-6. Após a estratificação, administrou-se aos animais N-acetilcisteína mais desferroxamina ou soro fisiológico a partir de 3 e 12 horas após a cirurgia. Em pacientes hipotensos, N-acetilcisteína mais desferroxamina ou placebo foram administrados dentro de 12 horas após o cumprimento dos critérios para inclusão. Resultados: O uso de N-acetilcisteína mais desferroxamina aumentou a sobrevivência no modelo com ligadura mais punção do ceco quando a administração ocorreu 3 e 12 horas após indução da sepse. Ao utilizar os níveis de interleucina-6 para separar os animais que receberam antioxidantes, o efeito protetor só foi observado nos animais que tinham níveis elevados de interleucina-6. O efeito antioxidante de N-acetilcisteína mais desferroxamina foi similar nos dois grupos, porém observou-se diminuição significante dos níveis plasmáticos de interleucina-6 no grupo que apresentava elevado nível de interleucina-6. Em comparação com pacientes tratados com antioxidantes no subgrupo que tinha baixos níveis plasmáticos de interleucina-6, aqueles que tinham níveis elevados de interleucina-6 tiveram menor incidência de lesão renal aguda, porém não foram diferentes em termos de severidade da lesão renal aguda ou da mortalidade na unidade de terapia intensiva. Conclusão: Direcionar a terapia antioxidante para um elevado fenótipo inflamatório selecionaria uma população responsiva.

ABSTRACT Objective: To examine the effectiveness of stratification to identify and target antioxidant therapy for animal models of lethal sepsis and in patients who develop sustained hypotension. Methods: Rats were subjected to sepsis induced by cecal ligation and puncture. Animals were divided into two groups: those with high and low plasma levels of interleukin-6. Following stratification, N-acetylcysteine plus deferoxamine or saline was administered to animals starting 3 and 12 hours after surgery. N-Acetylcysteine plus deferoxamine or placebo was administered within 12 hours of meeting the inclusion criteria in hypotensive patients. Results: N-Acetylcysteine plus deferoxamine increased survival in the cecal ligation and puncture model when administered 3 and 12 hours after sepsis induction. When dividing animals that received antioxidants using plasma interleukin-6 levels, the protective effect was observed only in those animals with high IL-6 levels. The antioxidant effect of N-acetylcysteine + deferoxamine was similar in the two groups, but a significant decrease in plasma interleukin-6 levels was observed in the high-interleukin-6-level group. Compared with patients treated with antioxidants in the low-interleukin-6 subgroup, those in the high-interleukin-6 subgroup had a lower incidence of acute kidney injury but were not different in terms of acute kidney injury severity or intensive care unit mortality. Conclusion: Targeting antioxidant therapy to a high inflammatory phenotype would select a responsive population.

Renoprotective Effects of Gallic Acid Against Gentamicin Nephrotoxicity Through Amelioration of Oxidative Stress in Rats

Abstract Gallic acid (GA), as a strong antioxidant, was selected in this study to investigate its possible nephroprotective effects against gentamicin (GM)-induced nephrotoxicity. Twenty-four rats were separated into three groups (n=8): group 1 (control group) received saline (0.5 mL/day), group 2 (GM group) received GM (100 mg/kg/day), and group 3 (treated group) received GM (100 mg/kg/day) and GA (100mg/kg/day). All treatments were performed intraperitoneally for 12 days. After 12 days, the rats were euthanized, and kidneys were removed immediately. For serum preparation, blood samples were collected before killing. Kidney paraffin sections were prepared from one of the kidneys and stained by the periodic acid-Schiff process. GA significantly decreased GM-induced renal histopathological injuries, including tubular necrosis, tubular cast, and leucocyte infiltration compared with the GM group. Additionally, GA significantly improved proteinuria, serum levels of urea and creatinine, and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with nephrotoxic animals. Furthermore, GA caused a significant improvement in the levels of cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cardiac risk ratios 1 and 2 in comparison with nephrotoxic animals. GA administration was observed to significantly improve the levels of lipid peroxidation, nitric oxide (NO), and glutathione (GSH) compared with the GM group. Finally, the activities and gene expression levels of catalase (CAT) and glutathione peroxidase (GPX) significantly increased following GA administration compared with the GM group. Our results indicated that GA has potential protective effects against GM nephrotoxicity by reducing oxidative stress in rats.

The protective effect of Ganoderma lucidum on testicular torsion/detorsion-induced ischemia-reperfusion (I/R) injury

Abstract Purpose To investigate the protective effect of Ganoderma lucidum on testicular torsion/detorsion (T/D)-induced ischemia-reperfusion (I/R) injury. Methods Thirty male Wistar albino rats were randomly categorized into 3 groups: Group 1: sham, Group 2 ( T/D): 2,5 hours of ischemia and 7 days of reperfusion, Group 3 (T/D+ G. lucidum ): 2,5 hours of ischemia and 7 days of reperfusion and 7 days of 20 mg/kg via gastric gavage G. lucidum polysaccharides per day. Biochemical assays of Malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), Glutathione (GSH) levels , histopathology and expression levels of VEGF and Bcl-2 with immunohistochemical methods were examined in testicular tissue. Results G. lucidum treatment was found to have prevented the T/D-induced I/R injury by decreasing MDA levels of the testis. SOD, CAT and GSH activities were decreased in group 2, while they were increased in group 3 (p<0.001) and significant improvement in the tube diameter was observed in group 3. Bcl-2-positive germinal cells were lowered in group 3 compared to the group 2. VEGF expression showed an increase in group 2, whereas it decreased in group 3. Conclusion The antioxidant G. lucidum is thought to induce angiogenesis by reducing the apoptotic effect in testicular torsion-detorsion.

High Mobility Group Box 1 and Heat Shock Protein-70 Expression Post (-)-Epigallocatechin-3-Gallate in East Java Green Tea Methanolic Extract Administration During Orthodontic Tooth Movement in Wistar Rats

Abstract Objective: To investigate the expression of High Mobility Group Box 1 (HMGB1) and Heat Shock Protein-70 (HSP-70) during orthodontic tooth movement (OTM) after (-)- Epigallocatechin-3-Gallate (EGCG) in East Java Green Tea (Camelia Sinensis) Methanolic Extract (GTME) administration in vivo. Material and Methods: 28 Wistar rats (Rattus Novergicus) was used and divided into 4 groups accordingly: K- without EGCG and OTM; K+ with OTM, without EGCG for 14 days; T1with OTM for 14 days and EGCG for 7 days; treatment group 2 (T2) with OTM and EGCG for 14 days. OTM animal model was achieved through the installation of the OTM device by means of NiTi close coil spring with 10g force placed between the first incisor and first maxillary molars. The samples were terminated on Day 14. The pre-maxillary was isolated for the immunohistochemical examination. Analysis of Variance (ANOVA) then continued with Tukey Honest Significant Difference (HSD) (p<0.05) was performed to analyze the data. Results: The highest HMGB1 and HSP-70 expression were found in the K+ group pressure side, meanwhile the lowest HMGB1 and HSP-70 expression were found in K- group tension side in the alveolar bone. There was a significant decrease of HMGB1 and HSP-70 expression in T2 compared to T1 and K+ with significant between groups (p<0.05; p=0.0001). Conclusion: The decreased expression of HMGB1 and HSP-70 in alveolar bone of OTM wistar rats due to post administration of GTME that consisted EGCG.

The effectiveness of eugenol against cisplatin-induced ototoxicity / A eficácia do eugenol contra a ototoxicidade induzida pela cisplatina

Abstract Introduction: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin. Objective: The aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity. Methods: The study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15 mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100 mg/kg eugenol intraperitoneal for five consecutive days. 100 mg/kg eugenol was administered to cisplatin + eugenol group for 5 days. On the third day, these rats were received a single dose of 15 mg/kg cisplatin. The control group was given 8 mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24 h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations. Results: Cisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection. Conclusion: The study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters.

Resumo Introdução: A ototoxicidade refere-se ao dano celular ou comprometimento da função da orelha interna associado a qualquer agente terapêutico ou substância química e ainda representa o principal efeito colateral que restringe o uso da cisplatina. Objetivo: O objetivo deste estudo foi realizar uma investigação bioquímica, funcional e histopatológica do potencial efeito protetor do eugenol contra a ototoxicidade induzida pela cisplatina. Método: O estudo foi realizado com 24 ratos fêmeas Sprague Dawley. Testes de emissões otoacústicas por produto de distorção foram realizados em todos os animais, os quais foram randomizados em quatro grupos iguais. Uma única dose intraperitoneal de 15 mg/kg de cisplatina foi administrada ao grupo cisplatina, enquanto o grupo eugenol recebeu 100 mg/kg de eugenol intraperitoneal por cinco dias consecutivos. Foram administrados 100 mg/kg de eugenol ao grupo cisplatina + eugenol durante 5 dias. No terceiro dia, estes ratos receberam uma dose única de 15 mg/kg de cisplatina. O grupo controle recebeu 8 mL/kg/dia de solução salina intraperitoneal por cinco dias. O teste de emissões otoacústicas por produto de distorção foi repetido 24 horas após a administração final do medicamento. Todos os animais foram sacrificados e as cócleas foram posteriormente utilizadas para exames bioquímicos e histopatológicos. Resultados: A cisplatina causou estresse oxidativo na cóclea, prejudicou a estrutura coclear e reduziu significativamente os níveis da relação sinal/ruído. A administração de eugenol juntamente com a cisplatina reverteu esses efeitos e forneceu proteção funcional, bioquímica e histopatológica. Conclusão: Os achados do estudo representam a primeira indicação na literatura de que o eugenol pode proteger contra a ototoxicidade, eleva os níveis de enzimas antioxidantes e diminui os níveis dos parâmetros oxidantes.

Inhibition of paracetamol-induced acute kidney damage in rats using a combination of resveratrol and quercetin / Inhibición de daño renal agudo inducido por paracetamol en ratas usando una combinación de resveratrol y quercetina

Paracetamol (also called acetaminophen, or APAP) overdose causes acute damage to the liver and kidneys in both humans and experimental animal models via the induction of the oxidative stress pathway. We sought to determine whether the combined antioxidants and anti-inflammatory compounds, resveratrol (RES) and quercetin (QUR) can protect against kidney injury induced by a toxic dose of APAP in a rat model of APAP-induced acute kidney injury. Rats were either received a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Harvested kidney tissues were prepared for light microscopy staining, and tissue samples were assayed for (i) biomarkers of oxidative stress and antioxidant, malondialdehyde (MDA) and superoxide dismutase (SOD); and (ii) biomarkers of inflammation, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Hematoxylin and eosin (H&E) stained images showed that APAP overdose induced acute kidney injury as demonstrated by widening of glomeruli space (Bowman space), tubular dilatation, numerous cellular debris in the renal tubules with tubular epithelial degeneration, and vacuolization, which were effectively protected by RES+QUR except a partial protection of the glomeruli space was observed. In addition, APAP significantly (p<0.05) modulated tissue levels of MDA, SOD, TNF-α, and IL-6, which were protected by RES+QUR. Furthermore, a significant (p<0.0001) positive correlation was observed between glomeruli space and TNF-α, (r=0.8899), IL-6 (r=0.8986), and MDA (r=0.8552), whereas glomeruli space scoring versus SOD showed negative correlation (r= - 0.7870). We conclude that resveratrol plus quercetin substantially protects against APAP-induced acute kidney injury in rats, possibly via the augmentation of antioxidants and inhibition of oxidative stress and inflammation.

La sobredosis de paracetamol (también llamado acetaminofen o APAP) causa un daño agudo en el hígado y los riñones, tanto en humanos como en modelos animales experimentales, a través de la inducción de la vía del estrés oxidativo. Intentamos determinar si los antioxidantes y los compuestos antiinflamatorios combinados, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal inducida por una dosis tóxica de APAP en un modelo de rata de lesión renal aguda inducida por APAP. Las ratas recibieron una dosis única de APAP (2 g / kg) antes de ser sacrificadas después de 24 horas o se trataron previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg), antes de ser tratadas, se administró una dosis única de APAP y luego fueron sacrificadas 24 horas después de la ingestión. Los tejidos renales recolectados se tiñeron con H-E y fueron observados a través de microscopía óptica. Las muestras de tejido se analizaron para (i) biomarcadores de estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (ii) biomarcadores de inflamación, factor de necrosis tumoral alfa (TNF-α) e interleucina-6 (IL-6). Las imágenes teñidas con H & E mostraron que la sobredosis de APAP indujo daño renal agudo como lo demuestra la ampliación del espacio glomerular, la dilatación tubular, numerosos desechos celulares en los túbulos renales con degeneración epitelial tubular y la vacuolización, que se protegieron eficazmente con RES + QUR Se observó una protección parcial del espacio glomerular. Además, APAP modificó significativamente (p <0.05) los niveles tisulares de MDA, SOD, TNF-α e IL-6, que estaban protegidos por RES + QUR. Además, se observó una correlación positiva significativa (p <0,0001) entre el espacio glomerular y el TNF-α, (r = 0,8899), IL-6 (r = 0,8986) y MDA (r = 0,8552), mientras que la puntuación del espacio glomerular versus SOD mostró correlación negativa (r = - 0,7870). Concluimos que el resveratrol más quercetina protege sustancialmente contra la lesión renal aguda inducida por APAP en ratas, posiblemente a través del aumento de antioxidantes y la inhibición del estrés oxidativo y la inflamación.

Duchenne muscular dystrophy: an historical treatment review / Distrofia muscular de Duchenne: revisão histórica do tratamento

ABSTRACT In this review, we discuss the therapies used in the treatment of patients with Duchenne muscular dystrophy since the first description of the disease. A short description is given of the various theories based on disease pathogenesis, which give the substrates for the many therapeutic interventions. A brief review of the methods of evaluation used in therapeutic trials is made. Of all the treatments, the only drugs that are still considered able to modify the course of the disease are the corticosteroids (prednisone/prednisolone/deflazacort). Other drugs (coenzyme Q10 and creatine) have had a little effect in a few functions without adverse reactions. Idebenone seems to improve the respiratory function in the long term. The trials with mRNA transcription, through nonsense mutations or exon 51 skipping, show some beneficial results in a few functional tests, but they are limited to a small set of DMD patients.

RESUMO Nesta revisão são discutidas as terapêuticas empregadas no tratamento da distrofia muscular de Duchenne desde a descrição da doença. Apresentamos as diversas teorias que fundamentaram as intervenções terapêuticas, com uma breve descrição dos tipos de avaliação empregados nos ensaios terapêuticos. Dentre todos os tratamentos, a única medicação que até agora modificou o curso da doença foram os corticosteroides (prednisona/prednisolona/deflazacort). A coenzima Q10 e creatina tiveram algum efeito pequeno em algumas funções e evolução da doença sem efeitos colaterais. O idebenone mostrou efeito benéfico na função respiratória em longo prazo. As tentativas de intervir no gene da distrofina utilizando técnicas de transcrição do mRNA através das mutações sem sentido e técnicas que pulam o exon 51 mostram resultado muito discreto em algumas provas funcionais e limitado a uma parcela pequena de casos.

Relación entre los antioxidantes y la calidad seminal / Relationship between antioxidants and semen quality

Los suplementos dietarios tales como vitaminas, minerales y antioxidantes mejoran la ingesta de nutrientes. Recientemente se ha descrito que, especialmente aquellos que contienen altas propiedades antioxidantes también mejoran la capacidad fértil. Se presenta el caso de un voluntario de 37 años con posible infertilidad masculina y se desea determinar el efecto del consumo de antioxidantes sobre la calidad seminal. Se realizó evaluación de los parámetros seminales convencionales y funcionales antes y después del uso del suplemento dietario Male Fertility. Se observó que el uso del suplemento dietario incrementó la concentración espermática, el potencial de membrana mitocondrial alto y la capacidad antioxidante del semen; además disminuyó la producción de 1as reactivas de oxígeno, la lipoperoxidación y la fragmentación de la cromática espermática. El suplemento dietario Male Fertility contiene altas concentraciones de vitamina A, C, E, B2, B3, B12, folato, zinc, selenio, acetil L-carnitina, coenzima Q10, L-metionina y licopeno. Se ha descrito que la ingesta de cada uno de estos compuestos tiene efectos positivos sobre la calidad seminal. El reporte de este caso permitió observar que el uso de suplementos dietarios ricos en vitaminas y antioxidantes puede mejorar la calidad seminal a través de la disminución del efecto adverso de las especies reactivas del oxígeno y por el incremento de las moléculas antioxidantes en el plasma seminal(AU)

Dietary supplements such as vitamins, minerals and antioxidants improve nutrient intake. Recently it has been described that, especially those containing high antioxidant properties also improve fertility. We report here the case of a 37-year-old volunteer with possible male infertility and we want to determine the effect of antioxidant consumption on semen quality. Evaluation of the conventional and functional seminal parameters was performed before and after the use of the Male Fertility dietary supplement. The use of this supplement was observed to increased the sperm concentration, the mitochondrial membrane potential and the antioxidant capacity of the semen. In addition, the production of oxygen reactants, lipoperoxidation and fragmentation of the spermatic chromatin decreased. The dietary supplement Male Fertility contains high concentrations of vitamin A, C, E, B2, B3, B12, folate, zinc, selenium, acetyl L-carnitine, coenzyme Q10, L-methionine and lycopene. The ingestion of each of these compounds has been described to have positive effects on seminal quality. The report of this case allowed to observe that the use of dietary supplements rich in vitamins and antioxidants can improve the seminal quality through the decrease of the adverse effect of the reactive oxygen species and by the increase of the antioxidant molecules in the seminal plasma(AU)

Efficacy of adjunctive Garcinia mangostana Linn (mangosteen) pericarp for bipolar depression: study protocol for a proof-of-concept trial

Objective: Bipolar depression is characterized by neurobiological features including perturbed oxidative biology, reduction in antioxidant levels, and a concomitant rise in oxidative stress markers. Bipolar depression manifests systemic inflammation, mitochondrial dysfunction, and changes in brain growth factors. The depressive phase of the disorder is the most common and responds the least to conventional treatments. Garcinia mangostana Linn, commonly known as mangosteen, is a tropical fruit. The pericarp's properties may reduce oxidative stress and inflammation and improve neurogenesis, making mangosteen pericarp a promising add-on therapy for bipolar depression. Methods: Participants will receive 24 weeks of either 1,000 mg mangosteen pericarp or placebo per day, in addition to their usual treatment. The primary outcome is change in severity of mood symptoms, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), over the treatment phase. Secondary outcomes include global psychopathology, quality of life, functioning, substance use, cognition, safety, biological data, and cost-effectiveness. A follow-up interview will be conducted 4 weeks post-treatment. Conclusion: The findings of this study may have implications for improving treatment outcomes for those with bipolar disorder and may contribute to our understanding of the pathophysiology of bipolar depression. Clinical trial registration: Australian and New Zealand Clinical Trial Registry, ACTRN12616000028404.