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Objective: To investigate the effect of vitexin on oxidative stress in rats with acute cerebral ischemia-reperfusion by regulating the pathway of nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE). Methods: A total of 54 SD rats were randomly divided into Sham group, model group, positive control (edaravone 0.56 mg/kg) group and vitexin low, medium, and high dose (10, 20, 40 mg/kg) groups. The rat models with acute cerebral ischemia were established except the Sham group. After reperfusion, rats in Sham group and model group were received ip saline. The edaravone group and vitexin groups were administered according to the corresponding dose, once every 8 h for a total of three times. The neurobehavioral scores of rats before and after intervention were compared. HE staining was used to detect the pathological changes of cerebral cortex. The levels of MDA, NO, SOD, and GSH in cerebral cortex of rats were detected by the kit. The mRNA and protein expression levels of Nrf2/ARE pathway related gene in rat cerebral cortex were detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western blotting. Results: Before and after intervention, there was no significant change in the neurobehavioral score of rats in the Sham group, the model group was higher than before intervention (P < 0.01), the edaravone group and the vitexin groups were lower than before intervention (P < 0.01), and there was a significant difference in the neurobehavioral score between the groups after intervention (P < 0.01). In the Sham group, the distribution of nerve cells was uniform and dense, and the morphology of cell body and nucleus was normal. In the model group, edaravone group and vitexin group, the arrangement of brain tissue was disordered and loose, in which liquefying necrosis and disappearance of cell structure were observed in the model group; in the low-dose group, the arrangement of cells was seriously disordered and loose. In the vitexin medium dose group and edaravone group, the area of liquefying necrosis was small, and most of the cells were normal; In the vitexin high dose group, only a few liquefying necrosis were found, the cell structure was basically normal, and the cell arrangement was slightly disordered. Compared with the Sham group, the levels of MDA and NO in the cerebral cortex of the model group were significantly increased (P < 0.01), the levels of SOD and GSH were significantly reduced (P < 0.01), and the expression levels of Nrf2 and γ-GCS mRNA were significantly increased (P < 0.01), the expression of cytoplasmic Nrf2 and γ-GCS proteins were significantly increased (P < 0.01), and the expression levels of nuclear Nrf2 and HO-1 proteins were significantly decreased (P < 0.01). Compared with the model group, the levels of MDA and NO in the cerebral cortex of rats in the edaravone group and low, medium and high dose groups of vitexin were significantly reduced (P < 0.01), and the levels of SOD and GSH were significantly increased (P < 0.01), Nrf2 and γ-GCS mRNA expression levels were significantly reduced (P < 0.01), cytoplasmic Nrf2, γ-GCS protein expressions were significantly reduced (P < 0.01), and nuclear Nrf2 and HO-1 protein expression levels were significantly increased (P < 0.01). And the levels of MDA, NO, SOD, GSH and Nrf2, γ-GCS, HO-1 mRNA and protein expression in rat cerebral cortex in each dose group were dose-dependent, with significant differences between groups (P < 0.01). Conclusion: Vitexin can alleviate oxidative stress in rats with acute cerebral ischemia-reperfusion. It is speculated that it is related to the regulation of Nrf2/ARE signaling pathway, the up-regulation of Nrf2 gene and protein expression, the promotion of its movement from cytoplasm to nucleus, the up-regulation of HO-1 expression, the inhibition of γ-GCS expression, and the enhancement of the body’s ability to response to oxidative stress.
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Introducción: En la actualidad se ha incrementado el uso de antioxidantes en el ámbito deportivo, sin embargo, no existe evidencia concluyente del efecto de estas sustancias en la mejora del desempeño físico de los atletas. Objetivo: Determinar la efectividad del uso de suplementos antioxidantes en la mejoría del desempeño físico atlético. Material y Métodos: Se realizó una revisión bibliográfica en bases de datos en línea como Pubmed, Scopus, la Web of Knowledge y el buscador google academic. Se incluyeron solo trabajos originales de estudios doble ciego relacionados con la intervención de un suplemento antioxidante. El periodo de revisión fue del 2009 a diciembre del 2017. Desarrollo: Se identificaron un total de 1053 artículos de los cuales 33 cumplieron con los criterios de inclusión de la revisión. De acuerdo con el tipo de suplemento, 2 correspondieron a vitaminas, 9 a polifenoles, 11 comerciales y los 9 restantes diversos. La antigüedad de los artículos analizados fue de 4,8 ± 2,4 años, en cuanto a la obsolescencia, determinado por el semiperiodo de Burton y Kleber y el índice de Price, fue 5,5 y 61,0 por ciento respectivamente. Conclusiones: Hasta el momento no existe evidencia sólida de que la ingesta de suplementos antioxidantes mejore el desempeño físico atlético. Son pocos los resultados positivos en alguna de las variables evaluadas, por tal motivo se requiere de mayor evidencia para poder dilucidar el efecto de los suplementos antioxidantes(AU)
Introduction: At present, the use of antioxidants in the sports field has increased. However, there is no conclusive evidence of the effect of these substances in improving the physical performance of athletes. Objective: To determine the effectiveness of antioxidant supplements in the improvement of athletic physical performance. Material and Methods: A bibliographic review was carried out through the search on online databases such as Pubmed, Scopus, the Web of Knowledge and Google Scholar search engine. Only original double-blind studies related to the intervention of an antioxidant supplement were included. The review period was from 2009 to December 2017. Development: A total of 1053 articles were identified, of which 33 met the inclusion criteria for the review. Regarding the type of supplement, 2 of them corresponded to vitamins, 9 to polyphenols, 11 to commercials, and the remaining 9 ones to several types. The historic period of the articles analyzed was 4.8 ± 2.4 years in terms of obsolescence, which was determined by the Burton and Kleber half-period and the Price index (5.5 and 61.0 percent respectively). Conclusions: To date, there is no solid evidence that the intake of antioxidant supplements improves physical athletic performance. There are few positive results in some of the evaluated variables; for this reason, more evidence is required to elucidate the effect of antioxidant supplements(AU)
Subject(s)
Humans , Male , Female , Sports/standards , Antioxidants/therapeutic useABSTRACT
Objective@#To investigate the effects of astragalus polysaccharides (APS) on insulin resistance and nuclear factor-related factor 2 (Nrf2) -antioxidant response element (ARE) pathway in gestational diabetic rats.@*Methods@#Pregnant Sprague Dawley (SD) rats were divided into normal pregnancy group (control group), model group [gestational diabetes mellitus (GDM) group], low-dose astragalus polysaccharide group (APS-L group), middle-dose astragalus polysaccharide group (APS-M group), high-dose astragalus polysaccharide group (APS-H group), pioglitazone group (Pio group). GDM rat model was established by intraperitoneal injection of streptozotocin (STZ). The levels of fasting blood glucose (FBG), fasting insulin (FINS), adiponectin (APN), tumor necrosis factor-α (TNF-α), Leptin, malondialdehyde (MDA), and superoxde dismutase (SOD) were measured before delivery and 20 days after pregnancy, then the insulin resistance index was calculated; histopathological changes of pancreas were observed by hematoxylin-eosin(HE) staining; the expressions of Nrf2, heme oxygenase-1 (HO-1), and γ-glutamyl cysteine synthase (γ-GCS)mRNAs were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR); Western blot was used to detect the expressions of Nrf2, HO-1, and γ-GCS proteins in pancreatic tissues.@*Results@#Compared with the control group, the levels of APN and SOD in GDM group were significantly lower (P<0.05); the levels of APN and SOD increased significantly after APS treatment, but there was no significant difference between APS-H group and Pio group; compared with the control group, the levels of TNF-α, Leptin, and MDA in the GDM group increased significantly (P<0.05); after APS treatment, the levels of TNF-α, Leptin, and MDA were significantly decreased (P<0.05), and with the increase of APS concentration, the effect of reduction was obvious, but there was no significant difference between APS-H group and Pio group; compared with the control group, the levels of FBG, FINS, insulin secretion index (IS), and insulin resistance index (IRI) in GDM group were significantly higher (P<0.05); compared with the GDM group, the levels of FBG, FINS, IS, and IRI in APS group were significantly lower, and with the increase of APS concentration, the effect of reduction was obvious, but there was no significant difference between APS-H group and Pio group; compared with the control group, the insulin sensitivity index (ISI) level in GDM group was significantly lower (P<0.05), while the level of ISI in APS group was significantly higher when treated with APS (P<0.05); the results of HE staining showed that the islet cells in the control group were regular round or oval with clear boundary; in the GDM group, the number of islets decreased significantly, while the islets atrophied without obvious boundary; after APS treatment, the number of islets increased, and the pathological damage was significantly reduced, the islet cells in Pio group showed a clear boundary after treatment; qRT-PCR showed that the expressions of Nrf2, HO-1, and γ-GCS in GDM group were significantly higher than those in control group (P<0.05), after APS treatment, the expression levels of Nrf2, HO-1, and γ-GCS decreased significantly (P<0.05), but there was no significant difference between APS-H group with Pio group; Western Blot results showed that the expressions of Nrf2, HO-1, and γ-GCS in GDM group were significantly higher than those in control group (P<0.05), after APS treatment, the levels of Nrf2, HO-1, and γ-GCS in APS group and Pio group were significantly lower than those in GDM group, but there was no significant difference between APS-H group with Pio group.@*Conclusions@#Astragalus polysaccharide can reduce insulin resistance in diabetic rats, which may play the role through Nrf2-ARE pathway.
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Nuclear factor E2-related factor 2 (Nrf2), an important transcription factor, is able to regulate Nrf2/antioxidant response element (ARE) signaling pathway, including the expressions of a series of cytoprotective proteins such as heme oxygenase-1 (HO-1), glutathione-S -transferase (GST) and quinine oxidoreductase 1 (NQO1), so as to maintain redox homeostasis and play a significant role in the prevention of cancer. However, the recent studies show that Nrf2 has another side. Nrf2 may promote the occurrence and development of tumors, and lead to drug resistance of tumor to chemotherapy, resulting in tremendous difficulties to the clinical treatment of tumors. Therefore, Nrf2/ARE signaling pathway is regarded as a breakthrough in overcoming drug resistance. This review summarizes the basic features and functions of Nrf2/ ARE signaling pathway, the dual functions of Nrf2, and the relationship between Nrf2 and multidrug resistance of tumors, all of which should facilitate the development of new strategies to improve chemotherapeutic efficacy.
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Objective To investigate the effects of astragalus polysaccharides (APS) on insulin resistance and nuclear factor-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway in gestational diabetic rats.Methods Pregnant Sprague Dawley (SD) rats were divided into normal pregnancy group (control group),model group [gestational diabetes mellitus (GDM) group],low-dose astragalus polysaccharide group (APS-L group),middle-dose astragalus polysaccharide group (APS-M group),high-dose astragalus polysaccharide group (APS-H group),pioglitazone group (Pio group).GDM rat model was established by intraperitoneal injection of streptozotocin (STZ).The levels of fasting blood glucose (FBG),fasting insulin (FINS),adiponectin (APN),tumor necrosis factor-α (TNF-α),Leptin,malondialdehyde (MDA),and superoxde dismutase (SOD) were measured before delivery and 20 days after pregnancy,then the insulin resistance index was calculated;histopathological changes of pancreas were observed by hematoxylin-eosin(HE) staining;the expressions of Nrf2,heme oxygenase-1 (HO-1),and γ-glutamyl cysteine synthase (γ-GCS)mRNAs were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR);Western blot was used to detect the expressions of Nrf2,HO-1,and γ-GCS proteins in pancreatic tissues.Results Compared with the control group,the levels of APN and SOD in GDM group were significantly lower (P ＜ 0.05);the levels of APN and SOD increased significantly after APS treatment,but there was no significant difference between APS-H group and Pio group;compared with the control group,the levels of TNF-α,Leptin,and MDA in the GDM group increased significantly (P ＜ 0.05);after APS treatment,the levels of TNF-α,Leptin,and MDA were significantly decreased (P ＜ 0.05),and with the increase of APS concentration,the effect of reduction was obvious,but there was no significant difference between APS-H group and Pio group;compared with the control group,the levels of FBG,FINS,insulin secretion index (IS),and insulin resistance index (IRI) in GDM group were significantly higher (P ＜ 0.05);compared with the GDM group,the levels of FBG,FINS,IS,and IRI in APS group were significantly lower,and with the increase of APS concentration,the effect of reduction was obvious,but there was no significant difference between APS-H group and Pio group;compared with the control group,the insulin sensitivity index (ISI) level in GDM group was significantly lower (P ＜0.05),while the level of ISI in APS group was significantly higher when treated with APS (P ＜ 0.05);the results of HE staining showed that the islet cells in the control group were regular round or oval with clear boundary;in the GDM group,the number of islets decreased significantly,while the islets atrophied without obvious boundary;after APS treatment,the number of islets increased,and the pathological damage was significantly reduced,the islet cells in Pio group showed a clear boundary after treatment;qRT-PCR showed that the expressions of Nrf2,HO-1,and γ-GCS in GDM group were significantly higher than those in control group (P ＜ 0.05),after APS treatment,the expression levels of Nrf2,HO-1,and γ-GCS decreased significantly (P ＜ 0.05),but there was no significant difference between APS-H group with Pio group;Western Blot results showed that the expressions of Nrf2,HO-1,and γ-GCS in GDM group were significantly higher than those in control group (P ＜ 0.05),after APS treatment,the levels of Nrf2,HO-1,and γ-GCS in APS group and Pio group were significantly lower than those in GDM group,but there was no significant difference between APS-H group with Pio group.Conclusions Astragalus polysaccharide can reduce insulin resistance in diabetic rats,which may play the role through Nrf2-ARE pathway.
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Abstract Purpose: To investigate the influence of lycium barbarum polysaccharides (LBP), a functional derivative from lycium barbarum, on septic kidney injury. Methods: The SD male rats were randomly divided into 8 groups. The concentration of IL-1β, IL-6, IL-8, TNF-α, NF-κB and ROS, in kidney cortex homogenates after 12 h treatments were determined by enzyme-linked immunosorbent assay and ROS test kit, respectively. Morphology observation of kidney tissue was conducted with HE staining. The mRNA and protein expression levels of Nrf2, HO-1, NQO1, NF-κB, and Keap1 in kidney tissues were determined by qRT-PCR and Western blot, respectively. Results: LPS treatment significantly increased the oxidative stress. After LBP treatment, the ROS content reduced significantly in a dose-depend manner. However, the levels of HO-1, NQO1 and Nrf2 as molecular elements that respond to oxidative stress were further increased. Also, administration of LBP increased the levels of NF-κB and Keap1, and decreased the levels of Nrf2 in the Keap 1-Nrf2∕ARE signaling pathway. By administrating the brusatol, the inhibition of Nrf2 enhanced the expression of NF-κB, inhibits the antioxidant responses, and further reverse the protective effect of LBP on the LPS induced septic kidney injury. Conclusion: Lycium barbarum polysaccharides can reduce inflammation and activate the antioxidant responses via regulating the level of pro-inflammatory cytokines and the Keap1-Nrf2/ARE signaling pathway.
Subject(s)
Animals , Male , Rats , Drugs, Chinese Herbal/therapeutic use , Oxidative Stress/drug effects , NF-E2-Related Factor 2/metabolism , Acute Kidney Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Signal Transduction/drug effects , Cytokines/drug effects , Disease Models, AnimalABSTRACT
Keratinocytes are constantly exposed to extracellular insults, such as ultraviolet B, toxic chemicals and mechanical stress, all of which can facilitate the aging of keratinocytes via the generation of intracellular reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a critical role in protecting keratinocytes against oxidants and xenobiotics by binding to the antioxidant response element (ARE), a cis-acting element existing in the promoter of most phase II cytoprotective genes. In the present study, we have attempted to find novel ethanol extract(s) of indigenous plants of Jeju island, Korea that can activate the Nrf2/ARE-dependent gene expression in human keratinocyte HaCaT cells. As a result, we identified that ethanol extract of Cirsium japonicum var. ussuriense Kitamura (ECJUK) elicited strong stimulatory effect on the ARE-dependent gene expression. Supporting this observation, we found that ECJUK induced the expression of Nrf2, hemoxygenase-1, and NAD(P)H:quinone oxidoreductase-1 and this event was correlated with Akt1 phosphorylation. We also found that ECJUK increased the intracellular reduced glutathione level and suppressed 12-O-tetradecanoylphorbol acetate-induced 8-hydroxyguanosine formation without affecting the overall viability. Collectively, our results provide evidence that ECJUK can protect against oxidative stress-mediated damages through the activation of Nrf2/ARE-dependent phase II cytoprotective gene expression.
Subject(s)
Humans , Aging , Antioxidant Response Elements , Cirsium , DNA Damage , DNA , Ethanol , Gene Expression , Glutathione , Keratinocytes , Korea , Oxidants , Phosphorylation , Reactive Oxygen Species , Stress, Mechanical , Transcription Factors , XenobioticsABSTRACT
Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels. .
Objetivo: Determinar os efeitos da administração aguda e crônica de metilprednisolona no estresse oxidativo, por meio da quantificação da peroxidação lipídica (POL) e do potencial antioxidante reativo total (PART), em pulmões de ratos. Métodos: Quarenta ratos Wistar foram divididos em quatro grupos: tratamento agudo, com ratos recebendo uma dose única de metilprednisolona (50 mg/kg i.p.); controle agudo, com ratos recebendo injeção unida de salina; tratamento crônico, com ratos recebendo metilprednisolona v.o. na água do bebedouro (6 mg/kg por dia durante 30 dias; e controle crônico, com ratos recebendo água de bebedouro normal). Resultados: Os níveis de PART foram significativamente maiores no grupo tratamento agudo que no grupo controle agudo, sugerindo uma melhora do sistema de defesa pulmonar. Os níveis de POL foram significativamente maiores no grupo tratamento crônico que no grupo controle crônico, indicando dano oxidativo no tecido pulmonar. Conclusões: Nossos resultados sugerem que o uso agudo de corticoides foi benéfico aos tecidos pulmonares, enquanto seu uso crônico não o foi. O uso crônico de metilprednisolona parece aumentar os níveis pulmonares da POL. .