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1.
Acta Cir Bras ; 34(7): e201900706, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531540

RESUMO

PURPOSE: To investigate the protective roles of pyracantha fortune fruit extract (PFE) on acute renal toxicity induced by cadmium chloride (CdCl2) in rats. METHODS: Rats were pretreated with PFE and consecutively injected with CdCl2 (6.5 mg/kg) for 5 days. RESULTS: The concentration of Cd, kidney weight, malondialdehyde (MDA), and nitric oxide (NO) production were remarkably increased in CdCl2 group as well as the levels of plasma uric acid, urea, and creatinine (P < 0.001). However, the body weight and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione peroxidase (GR) levels were markedly reduced by CdCl2 treatment (P < 0.001). Histological manifestations of renal tissue showed severely adverse changes. Moreover, CdCl2 treatment significantly decreased the B-cell lymphoma-2 (Bcl-2) expression while increased the Bcl-2-Associated X Protein (Bax), tumor necrosis factor-α (TNF-α) expression (P < 0.001). Additionally, the expression of Nrf2/Keap 1 related proteins Keap-1 gained a significant increase (P < 0.001), whereas the Nrf2, HO-1, γ-GCS, GSH-Px and NQO1 expression decreased by CdCl2 treatment (P < 0.05). These rats were pretreated with PFE to improve the changes caused by CdCl2 treatment. CONCLUSION: PFE could protect the kidney against acute renal toxicity induced by CdCl2.


Assuntos
Antioxidantes/farmacologia , Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Rim/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pyracantha/química , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Frutas/química , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo
2.
Adv Exp Med Biol ; 1155: 185-196, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468397

RESUMO

In the present study, we evaluated the antioxidant and anti-stress activities of taurine in electric foot-shock stress model rats. Taurine supplementation markedly increased the hepatic glutathione (GSH) levels, compared to the levels in the stress group. In addition, activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were improved in the taurine-treated group. Plasma cortisol and dehydroepiandrosterone-sulfate (DHEA-S) levels were significantly reduced in the taurine-supplemented group compared to those in the stress group. In contrast, the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were markedly increased in the taurine or betaine-treated group compared to those in the stress group. It may be concluded that taurine produces beneficial effects in the form of antioxidant status and biochemical alterations in foot-shock-induced acute stress in rats.


Assuntos
Antioxidantes/farmacologia , Fígado/efeitos dos fármacos , Estresse Fisiológico , Taurina/farmacologia , Animais , Catalase/metabolismo , Sulfato de Desidroepiandrosterona/sangue , Estimulação Elétrica , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Hidrocortisona/sangue , Ácido Hidroxi-Indolacético/sangue , Fígado/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Serotonina/sangue
3.
Adv Exp Med Biol ; 1155: 739-746, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468444

RESUMO

The herbicide Paraquat induce oxidative stress-mediated lung injury. Taurine is a well-known antioxidant. This study was designed to explore the effect of taurine on paraquat-induced injury and its related mechanism in A549 cells. The cells were pretreated with various concentrations of taurine for 30 min prior to paraquat exposure. 24 h later, cell viability was examined by the MTT assay. The level of glutathione (GSH) and the activity of glutathione peroxidase (GPx) were analyzed. The results show that taurine treatment significantly attenuates the decrease in cell viability mediated by paraquat in A549 cells. Taurine also reversed paraquat-induced disturbances in GSH content and GPx activity. Taurine exerts protection against paraquat-mediated A549 cell toxicity likely through modulation of oxidative stress.


Assuntos
Células Epiteliais/efeitos dos fármacos , Estresse Oxidativo , Paraquat/toxicidade , Taurina/farmacologia , Células A549 , Células Cultivadas , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Pulmão/citologia
4.
Chem Biol Interact ; 311: 108777, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31376360

RESUMO

Nicorandil ameliorated doxorubicin-induced nephrotoxicity; this study aimed to show and explain the mechanism of this protection. A precise method was elucidated to study the effect of nicorandil on doxorubicin-induced nephrotoxicity in rats depending on the critical inflammation pathway TLR4/MAPK P38/NFκ-B. Adult male rats were subdivided into four groups. The 1st group was normal control, the 2nd group received nicorandil (3 mg/kg; p.o., for 4 weeks), the 3rd group received doxorubicin (2.6 mg/kg, i.p., twice per week for 4 weeks), and the fourth group was combination of doxorubicin and nicorandil for 4 weeks. Nephrotoxicity was assessed by biochemical tests through measuring Kidney function biomarkers such as [serum levels of urea, creatinine, albumin and total protein] besides renal kidney injury molecule-1 (KIM-1) and cystatin C], oxidative stress parameters such as [renal tissue malondialdehyde (MDA), reduced glutathione (GSH), SOD, catalase and nrf-2], mediators of inflammation such as [Toll like receptor 4 (TLR-4), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), p38 MAPK, Interleukin 1 beta (IL-1 ß), and Tumor necrosis factor alpha (TNF-α)] and markers of apoptosis [BAX and Bcl-2 in renal tissue]. Finally, our data were supported by histopathology examination. Nicorandil pretreatment resulted in a significant decrease in nephrotoxicity biomarkers, oxidative stress markers, inflammatory mediators and prevented apoptosis through decreasing BAX and increasing Bcl-2 in renal tissues. Nicorandil prevented all the histological alterations caused by doxorubicin. Nicorandil is a promising antidote against doxorubicin-induced nephrotoxicity by neutralizing all toxicity mechanisms caused by doxorubicin through normalizing inflammatory cascade of TLR4/MAPK P38/NFκ-B.


Assuntos
Doxorrubicina/toxicidade , Rim/efeitos dos fármacos , Nicorandil/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Nitrogênio da Ureia Sanguínea , Moléculas de Adesão Celular/sangue , Creatinina/sangue , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
J Agric Food Chem ; 67(32): 9032-9038, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31334646

RESUMO

It is estimated that approximately 200 million people are exposed to arsenic levels above the World Health Organization provisional guideline value, and various agencies have indicated the need to reduce this exposure. In view of the difficulty of removing arsenic from water and food, one alternative is to reduce its bioavailability (the amount that reaches the systemic circulation after ingestion). In this study, dietary components [glutathione, tannic acid, and Fe(III)] were used to achieve this goal. As(III) or As(V) (1 mg/kg body weight) was administered daily to BALB/c mice, along with the dietary components, for 15 days. The results confirm the efficacy of Fe(III) and glutathione as reducers of arsenic bioavailability and tissue accumulation. Also, these treatments did not result in reductions of Ca, K, P, and Fe contents in the liver. These data suggest that use of these two compounds could be part of valid strategies for reducing inorganic arsenic exposure in chronically exposed populations.


Assuntos
Arsenicais/metabolismo , Compostos Férricos/química , Glutationa/química , Animais , Arsenicais/química , Disponibilidade Biológica , Exposição Dietética/análise , Exposição Dietética/prevenção & controle , Compostos Férricos/metabolismo , Contaminação de Alimentos/análise , Glutationa/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oryza/química , Oryza/metabolismo
6.
Chem Biol Interact ; 310: 108741, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31299238

RESUMO

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in redox homeostasis. Activation of Nrf2 pathway by natural molecules effectively inhibits oxidants and toxicants-induced redox imbalance, and thus is able to intervene the onset and progression of many human diseases. In our previous study, a chalcone named as artocarmitin B (ACB), formed by artocarmitin A (ACA) and a trans-feruloyl substituent, was found to be a potential Nrf2 activator. In the present research, we found that ACB up-regulated the expressions of Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutamate-cysteine ligase, modifier subunit (GCLM), inhibited Nrf2 degradation and promoted Nrf2 translocation to the nucleus under non-toxic doses. Moreover, ACB enhanced intracellular antioxidant capability in human lung epithelial cells through up-regulating reduced glutathione (GSH) level. Furthermore, ACB-induced activation of Nrf2 was related to the kinase pathways, including mitogen-activated protein kinase (MAPK), protein kinase C (PKC), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and protein kinase R-like endoplasmic reticulum kinase (PERK). In terms of activation of Nrf2 pathway, ACB was more potent than ACA and ferulic acid (FA) individually or in combination. Collectively, our results indicate that ACB is an novel Nrf2 activator and enhances intracellular antioxidant capacity in human lung epithelial cells.


Assuntos
Antioxidantes/farmacologia , Chalcona/farmacologia , Células Epiteliais/metabolismo , Pulmão/citologia , Fator 2 Relacionado a NF-E2/metabolismo , Chalcona/uso terapêutico , Glutationa/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Transdução de Sinais
7.
Chem Commun (Camb) ; 55(65): 9629-9632, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31353368

RESUMO

Excessive accumulation of reducing agents in the ER leads to a constitutively high UPR. And the co-function of GSH, Cys and HOCl in biological processes is not well understood. To address this, a TP probe, NPCC, was developed for monitoring reductive stress in the ER. It can also distinguish cancer cells from normal cells.


Assuntos
Cumarínicos/química , Estresse do Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/química , Pirazóis/química , Animais , Cumarínicos/síntese química , Cisteína/química , Cisteína/metabolismo , Corantes Fluorescentes/síntese química , Glutationa/química , Glutationa/metabolismo , Cabras , Células HeLa , Humanos , Ácido Hipocloroso/química , Ácido Hipocloroso/metabolismo , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Oxirredução , Pirazóis/síntese química , Peixe-Zebra
8.
BMC Infect Dis ; 19(1): 600, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288760

RESUMO

BACKGROUND: Oxidative stress plays a vital role in the pathogenesis of both Sickle Cell Disease (SCD) and Plasmodium falciparum malaria. However, there are limited studies on the effect of P. falciparum malaria infection on oxidative stress in SCD patients. METHODS: A cross-sectional study was undertaken to compare levels of biomarkers of oxidative stress in isolates from SCD patients with uncomplicated P.falciparum malaria. The biomarkers namely: malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx) were determined in plasma samples from SCD malaria positive, malaria positive, SCD malaria negative and healthy control participants. The genetic diversity of P.falciparum was determined by nested polymerase chain reaction of merozoite surface protein-2 (MSP-2) gene. RESULTS: Out of 207 participants, 54 (26%) were SCD malaria positive, 51 (24%) malaria positive, 51 (24%) SCD controls and 51 (24%) healthy control individuals. The mean concentration of MDA was significantly higher in SCD malaria positive than SCD controls (P < 0.0001). In contrast, the mean concentration of GSH (P < 0.0001) and GPx (P < 0.0001) were significantly lower in SCD malaria than SCD controls. Although not significantly different, the mean concentration of MDA was higher (P = 0.0478), but the geometric mean parasite density (P = 0.2430) and multiplicity of infection (P = 0.3478) were lower in SCD malaria samples than in malaria samples. The most prevalent MSP2 allelic family was IC3D7 in SCD malaria (72%) and Malaria (76%) samples. The biomarkers of oxidative stress were not significantly different between IC3D7 and FC27 allelic families of MSP2. CONCLUSION: We identified severe oxidative stress in Sickle cell disease patients with uncomplicated P.falciparum malaria.


Assuntos
Anemia Falciforme/diagnóstico , Malária Falciparum/diagnóstico , Estresse Oxidativo , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/patologia , Antígenos de Protozoários/genética , Biomarcadores/metabolismo , Catalase/metabolismo , Estudos Transversais , Teste em Amostras de Sangue Seco , Feminino , Variação Genética , Genótipo , Glutationa/metabolismo , Humanos , Malária Falciparum/parasitologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/genética , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/genética , Índice de Gravidade de Doença , Uganda
9.
Int J Nanomedicine ; 14: 4723-4739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308655

RESUMO

Background: Much consideration has been paid to the toxicological assessment of nanoparticles prior to clinical and biological applications. While in vitro studies have been expanding continually, in vivo investigations of nanoparticles have not developed a cohesive structure. This study aimed to assess the acute toxicity of different concentrations of chitosan-coated silver nanoparticles (Ch-AgNPs) in main organs, including liver, kidneys, and spleen. Materials and methods: Twenty-eight male albino rats were used and divided into 4 groups (n=7). Group 1 was kept as a negative control group. Groups 2, 3, and 4 were treated intraperitoneally with Ch-AgNPs each day for 14 days at doses of 50, 25, and 10 mg/kg body weight (bwt) respectively. Histopathological, morphometric and immunohistochemical studies were performed as well as oxidative stress evaluations, and specific functional examinations for each organ were elucidated. Results: It was revealed that Ch-AgNPs induced dose-dependent toxicity, and the repeated dosing of rats with 50 mg/kg Ch-AgNPs induced severe toxicities. Histopathological examination showed congestion, hemorrhage, cellular degeneration, apoptosis and necrosis in hepatic and renal tissue as well as lymphocytic depletion with increasing tangible macrophages in the spleen. The highest levels of malondialdehyde, alanine aminotransferase, aspartate aminotransferase (MDA, ALT, AST) and the lowest levels of reduced glutathione, immunoglobulin G, M and total protein (GSH, IgG, IgM, TP) were observed in this group. On the other hand, repeated dosing with 25 mg/kg induced mild to moderate disturbance in the previous parameters, while there was no significant difference in results of pathological examination and biochemical tests between the control group and those treated with 10 mg/kg bwt Ch-AgNPs. Conclusion: Chitosan-coated silver nanoparticles induce dose-dependent adverse effects on rats.


Assuntos
Quitosana/química , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Caspase 3/metabolismo , Creatinina/sangue , Glutationa/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Nanopartículas Metálicas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Wistar , Baço/efeitos dos fármacos , Baço/patologia
10.
Chem Biol Interact ; 311: 108758, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31348919

RESUMO

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in children. It is diagnosed by two main behavioral phenotypes i.e. social-communication impairments and repetitive behavior. ASD is complex disorder with unsolved etiology due to multiple genes involvement, epigenetic mechanism and environmental factors. The clinical and preclinical studies have been indicating the association of propionic acid with autism spectrum disorder. Numerous studies suggest the potential therapeutic effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in different brain disorders. This research evaluates the utility of selective agonist of PPAR-γ, pioglitazone in postnatal propionic acid induced ASD related symptomatology in male Wistar rats. PPA (250 mg/kg, p.o.) was administered to male offspring for three consecutive days from postnatal 21st day to 23rd day. PPA induced social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity in rats. Also, postnatal propionic acid-treated rats showed higher levels of oxidative stress (increased in thiobarbituric acid reactive species and decreased in reduced glutathione) as well as inflammation (increased in interleukin-6, tumor necrosis factor-alpha and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. The rats were treated daily with pioglitazone (10 mg/kg and 20 mg/kg, p.o.) from postnatal 24th day to end of the study. Treatment with pioglitazone, significantly attenuated the postnatal propionic acid-induced social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, pioglitazone also reduced the postnatal propionic acid-induced oxidative stress and neuroinflammation in aforementioned brain regions. Hence, pioglitazone improved the propionic acid-induced neurobehavioral and biochemical impairments in rats.


Assuntos
Transtorno do Espectro Autista/patologia , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/agonistas , Pioglitazona/farmacologia , Animais , Ansiedade/prevenção & controle , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Glutationa/metabolismo , Inflamação/prevenção & controle , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Locomoção/efeitos dos fármacos , Masculino , PPAR gama/metabolismo , Fenótipo , Pioglitazona/uso terapêutico , Propionatos/toxicidade , Ratos , Ratos Wistar
11.
Life Sci ; 232: 116634, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279782

RESUMO

AIM: Here, we evaluated the possible protective effects of oleuropein, the major phenolic constituent in virgin olive oil against glycerol-induced acute kidney injury (AKI) in rats. MAIN METHODS: Twenty-eight Sprague Dawley rats were allocated equally into four groups as follows: control group, oleuropein group (50 mg/kg body weight), AKI group and the oleuropein + AKI group. AKI was induced by injecting 50% glycerol (10 ml/kg body weight) intramuscularly. KEY FINDINGS: Glycerol injection increased the kidney relative weight as well as rhabdomyolysis (RM)- and AKI-related index levels, including the levels of creatine kinase, lactate dehydrogenase, creatinine, urea, and Kim-1 expression. Additionally, alteration in oxidative conditions in renal tissue was recorded, as confirmed by the elevated malondialdehyde and nitric oxide levels and the decreased glutathione content. Concomitantly, the protein and mRNA expression levels of antioxidant enzymes were suppressed. Moreover, Nfe2l2 and Hmox1 mRNA expression was also downregulated. Glycerol triggered inflammatory reactions in renal tissue, as evidenced by the increased pro-inflammatory cytokines and Ccl2 protein and mRNA expression, whereas myeloperoxidase activity was increased. Furthermore, glycerol injection enhanced apoptotic events in renal tissue by increasing the expression of the pro-apoptotic proteins and decreasing that of anti-apoptotic. However, oleuropein administration reversed the molecular, biochemical, and histological alterations resulting from glycerol injection. SIGNIFICANCE: Our data suggest that oleuropein has potential as an alternative therapy to prevent or minimize RM incidence and subsequent development of AKI, possibly due to its potent anti-stress, anti-inflammatory, and anti-apoptotic effects.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Iridoides/farmacologia , Lesão Renal Aguda/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Creatina Quinase/metabolismo , Creatinina/metabolismo , Glutationa/metabolismo , Glicerol/efeitos adversos , Glicerol/farmacologia , Inflamação/metabolismo , Iridoides/metabolismo , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Rabdomiólise/complicações
12.
Ecotoxicol Environ Saf ; 182: 109416, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31301596

RESUMO

The main objectives of this study were to purify the glutathione S-transfereses (GSTs) and assess the effect of high doses of acrylamide (ACR) on male albino Wistar rat liver, kidney, testis and bran GST activities, and expression analysis of GST. ACR (50 mg/300 ml) was ingested for 40 days (20 doses) in drinking water on alternative days, on 40 day post ingestion the control and treated tissues were collected for GST purification by affinity column and biochemical characterization of GSTs by substrate specificities, and GST expression by immuno dot blots. In the analysis of the purified GSTs, we observed that liver GSTs were resolved in to three bands known as Yc, Yb and Ya; kidney GSTs were resolved in to two bands known as Yc and Ya; testis and brain GSTs were resolved as four bands known as Yc, Yb, Yß and Yδ on 12.5% sodium dodecyl sulfate polyacrylamide gel (SDS PAGE). In the analysis of biochemical characterization, we observed a significant decrease (p < 0.05) in the specific activities of liver GST isoforms with the substrates 1-chloro 2,4-dinitrobenzene (CDNB), bromosulfophthalein (BSP), p-nitrophenyl acetate (pNPA), p-nitrobenzyl chloride (pNBC) and cumene hydroperoxide (CHP), but showed no activity with ethacrynic acid (ECA) and significant decrease (p < 0.05) in the specific activities of kidney GST isoforms with the substrates CDNB, pNPA, pNBC and CHP, but showed no activity with BSP and ECA, and a significant decrease (p < 0.05) in the specific activities of testis and brain GST isoforms with the substrates CDNB, BSP, pNPA, pNBC, ECA and CHP. In the analysis of immuno dot blots, we observed a decreased expression of liver, kidney, testis and brain GSTs. Through the affinity purification and biochemical characterization, we observed a tissue specific distribution of GSTs that is liver GSTs possess Yc, Yb and Ya sub units known as alpha (α) and mu (µ) class GSTs; kidney GSTs possess Yc and Ya sub units known as (α) alpha class GST; testis and brain GSTs possess Yc, Yb, Yß and Yδ sub units known as alpha (α), mu (µ) and pi (π) class GSTs. Purification studies, biochemical characterization and immuno dot blot analysis were revealed the GSTs were sensitive to high doses of ACR and the high level exposure to ACR cause the damage of detoxification function of GST due to decreased expression and hence lead to cellular dysfunction of vital organs.


Assuntos
Acrilamida/toxicidade , Glutationa Transferase/metabolismo , Animais , Eletroforese em Gel de Poliacrilamida , Glutationa/metabolismo , Isoenzimas , Rim/metabolismo , Fígado/metabolismo , Masculino , Nitrobenzenos , Nitrofenóis , Ratos , Ratos Wistar , Especificidade por Substrato , Testículo/metabolismo , Distribuição Tecidual
13.
Chemosphere ; 233: 954-965, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31340423

RESUMO

Heavy metals such as cadmium and zinc constitute major pollutants in coastal areas and frequently accumulate in salt marshes. The wetland halophyte plant species Kosteletzkya pentacarpos is a promising species for phytostabilization of contaminated areas. In order to assess the role of the antisenescing phytohormone cytokinin in heavy metal resistance in this species, seedlings were exposed for two weeks to Cd (10 µM), Zn (100 µM) or Cd + Zn (10 µM + 100 µM) in the presence or absence of 50 mM NaCl and half of the plants were sprayed every two days with the cytokinin trans-zeatine riboside (10 µM). Zinc reduced the endogenous cytokinin concentration. Exogenous cytokinin increased plant growth, stomatal conductance, net photosynthesis and total ascorbate and reduced oxidative stress estimated by malondialdehyde in Zn-treated plants maintained in the absence of NaCl. Heavy metal induced an increase in the senescing hormone ethylene which was reduced by cytokinin treatment. Plants exposed to the mixed treatment (Cd + Zn) exhibited a specific hormonal status in relation to accumulation of abscisic acid and depletion of salicylic acid. Non-protein thiols (glutathione and phytochelatins) accumulated in response to Cd and Cd + Zn. It is concluded that toxic doses of Cd and Zn have different impacts on the plant behavior and that the simultaneous presence of the two elements induces a specific physiological constraint at the plant level. Salinity helps the plant to cope with heavy metal toxicities and the plant hormone cytokinin assumes key function in Zn resistance but its efficiency is lower in the presence of NaCl.


Assuntos
Cádmio/toxicidade , Citocininas/metabolismo , Hibiscus/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Cloreto de Sódio/farmacologia , Zinco/toxicidade , Ácido Abscísico/análise , Glutationa/metabolismo , Hibiscus/crescimento & desenvolvimento , Fotossíntese/efeitos dos fármacos , Fitoquelatinas/metabolismo , Desenvolvimento Vegetal/efeitos dos fármacos , Ácido Salicílico/análise , Salinidade , Plântula/fisiologia , Poluentes Químicos da Água/toxicidade , Áreas Alagadas
14.
Pestic Biochem Physiol ; 157: 60-68, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153478

RESUMO

A series of novel substituted oxazole isoxazole carboxamides derivatives were designed on the basis of active subunit combination. Forty-four novel compounds were synthesized by an efficient one-pot procedure under microwave irradiation. The bioactivity was evaluated as herbicide safener against the injury of chlorsulfuron. It was found that most of the synthesized compounds displayed remarkable protection against chlorsulfuron via enhanced glutathione content and glutathione S transferase activity. Especially compound I-11 exhibited better bioactivity than the safeners isoxadifen-ethyl and R-28725. Molecular docking simulations suggested that the target compounds could compete with chlorsulfuron in the active site of acetolactate synthase, which could explain the protective effects of safeners. The present work demonstrates that the target compounds containing oxazole isoxazole groups could be considered as potential candidates for developing novel safeners in the future.


Assuntos
Herbicidas/química , Herbicidas/farmacologia , Isoxazóis/química , Oxazóis/química , Sulfonamidas/farmacologia , Triazinas/farmacologia , Acetolactato Sintase/genética , Acetolactato Sintase/metabolismo , Ativação Enzimática/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Relação Estrutura-Atividade , Zea mays/enzimologia
15.
J Sci Food Agric ; 99(13): 6097-6107, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31250448

RESUMO

BACKGROUND: Reactive oxygen species (ROS) can cause DNA damage. Rice protein (RP) inhibits ROS accumulation. However, a link between the reduction of ROS-derived DNA damage and the intake of RP is far from clear. The main objective of this study is to elucidate the effects of RPs on the reduction of DNA damage in growing and adult rats. RESULTS: An intake of RP for 2 weeks significantly reduced the hepatic accumulation of ROS and 8-hydroxydeoxyguanosine (8-OHdG) in growing and adult rats, whereas the hepatic p53 content was markedly increased by RPs. After 2 weeks' feeding, the mRNA levels and protein expressions of p53, ataxia-telangiectasia mutated (ATM), and Checkpoint kinase 2 (Chk2) were up-regulated by RPs, whereas Murine Double Minute 2 (MDM2) expressions were markedly inhibited by RPs, resulting in more p53 being translocated into the nucleus. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) was activated by RP by reducing Kelch-like ECH-associated protein 1 (Keap1), resulting in the up-regulation of antioxidant expressions of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in RP groups. CONCLUSION: Rice protein can exert an endogenous antioxidant activity to reduce ROS-derived DNA damage by activating the Nrf2-Keap1 pathway. This study suggests that the activation of the ATM-Chk2-p53 pathway might be one of the mechanisms exerted by RP for reducing DNA damage in growing and adult rats. © 2019 Society of Chemical Industry.


Assuntos
Antioxidantes/metabolismo , Dano ao DNA , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Catalase/genética , Catalase/metabolismo , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/genética
16.
J Toxicol Sci ; 44(6): 405-414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31168027

RESUMO

Several studies have demonstrated the chemopreventive role of ketoconazole in animal models of liver injury. However, the underlying molecular mechanisms of this hepatoprotective effect are poorly understood. The present study assessed the potential of ketoconazole to enhance resistance to carbon tetrachloride-induced hepatotoxicity in vivo in a rat model. Ketoconazole pretreatment adult male rats were intraperitoneally injected with carbon tetrachloride for 24 hr and various hepatic parameters were analyzed. We observed decreased serum transaminases activity, reduced nuclear RelA/p65 expression, and suppressed production of pro-inflammatory cytokines in the liver tissue. Histopathological examination demonstrated ketoconazole pretreatment to extensively prevent liver injury. In addition, it significantly increased nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) protein expression, glutathione (GSH) to oxidized glutathione (GSSG) ratio, and antioxidant enzymes gene expression. These results suggest that ketoconazole pretreatment ameliorates carbon tetrachloride-induced acute liver injury in rats, signifying its anti-inflammatory and antioxidant functions.


Assuntos
Anti-Inflamatórios/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cetoconazol/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/metabolismo , Glutationa/metabolismo , Cetoconazol/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
17.
Artigo em Russo | MEDLINE | ID: mdl-31156222

RESUMO

AIM: To assess the activity of glutathione reductase (GR) and glutathione-S-transferase (GST) in blood cells of patients at clinical high-risk (HR) state for psychosis, in first-episode patients with schizophrenia and schizoaffective disorder (SD), and control group, and to seek correlations of these biochemical parameters with clinical assessments in patients. MATERIAL AND METHODS: The study included male patients at HR (n=21, 16-25 years old), first-episode patients with schizophrenia (F20, n=14, 18-25 years old) and SD (F25, n=20, 16-25 years old), and 12 people of the control group (19-25 years old). Psychometric scales (SOPS, HDRS, and PANSS) and psychopathological methods were employed. GR and GST enzymatic activities were determined spectrophotometrically. RESULTS: The activities of platelet GR and GST in all groups of patients both before and after treatment were lower than in controls (p<0.01). The platelet GST activity was lower in patients at HR compared to patients with schizophrenia before treatment and lower than in patients with SD after treatment (p<0.05), it was higher in patients with schizophrenia than in patients with SD before treatment (p<0.05). Erythrocyte GST activity in patients with HR was lower than in patients with SD after treatment, and in the latter it exceeded that in patients with schizophrenia and controls (p<0.05). Complex and different patterns of changes in the activities of erythrocyte and platelet GR and GST in patients with schizophrenia spectrum disorders, occurring both before the first psychotic episode in the initial stage of disease, and in the first-episode patients, were detected. CONCLUSION: The activity of glutathione-converting enzymes in endogenous psychoses of the schizophrenic spectrum, including its early stages, can be used as a biomarker for predicting the development of psychosis, the course of disease, and as criteria for evaluation of therapeutic response to antipsychotic treatment.


Assuntos
Glutationa , Transtornos Psicóticos , Esquizofrenia , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Feminino , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Humanos , Masculino , Transtornos Psicóticos/metabolismo , Esquizofrenia/metabolismo , Adulto Jovem
18.
Environ Pollut ; 251: 961-969, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234263

RESUMO

Phycoremediation technologies significantly contribute to solving serious problems induced by heavy metals accumulation in the aquatic systems. Here we studied the mechanisms underlying Al stress tolerance in two diazotrophic cyanobacterial species, to identify suitable species for Al phycoremediation. Al uptake as well as the physiological and biochemical responses of Anabaena laxa and Nostoc muscorum to 7 days Al exposure at two different concentrations i.e., mild (100 µM) and high dose (200 µM), were investigated. Our results revealed that A. laxa accumulated more Al, and it could acclimatize to long-term exposure of Al stress. Al induced a dose-dependent decrease in photosynthesis and its related parameters e.g., chlorophyll content (Chl a), phosphoenolpyruvate carboxylase (PEPC) and Ribulose‒1,5‒bisphosphate carboxylase/oxygenase (RuBisCo) activities. The affect was less pronounced in A. laxa than N. muscorum. Moreover, Al stress significantly increased cellular membrane damage as indicated by induced H2O2, lipid peroxidation, protein oxidation, and NADPH oxidase activity. However, these increases were lower in A. laxa compared to N. muscorum. To mitigate the impact of Al stress, A. laxa induced its antioxidant defense system by increasing polyphenols, flavonoids, tocopherols and glutathione levels as well as peroxidase (POX), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPX) enzymes activities. On the other hand, the antioxidant increases in N. muscorum were only limited to ascorbate (ASC) cycle. Overall, high biosorption/uptake capacity and efficient antioxidant defense system of A. laxa recommend its feasibility in the treatment of Al contaminated waters/soils.


Assuntos
Alumínio/metabolismo , Anabaena/metabolismo , Antioxidantes/metabolismo , Biodegradação Ambiental , Nostoc muscorum/metabolismo , Fotossíntese/efeitos dos fármacos , Ácido Ascórbico/metabolismo , Catalase/metabolismo , Clorofila/metabolismo , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Peroxidases/metabolismo , Fosfoenolpiruvato Carboxilase/metabolismo , Ribulose-Bifosfato Carboxilase/metabolismo
19.
Chem Commun (Camb) ; 55(56): 8122-8125, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31237279

RESUMO

Pi-class glutathione S-transferase (GSTP1) is a molecular marker enzyme whose expression level is altered in various malignant tumour tissues. Herein, we report the first highly selective fluorogenic GSTP1 substrate, Ps-TG, and its membrane-permeable derivative Ps-TAc, for specific visualization of intracellular GSTP1 activity in cancer cells or epigenetically regulated GSTP1 expression.


Assuntos
Epigênese Genética , Corantes Fluorescentes/metabolismo , Glutationa S-Transferase pi/metabolismo , Glutationa/metabolismo , Humanos , Células MCF-7 , Espectrometria de Fluorescência , Especificidade por Substrato
20.
Plant Sci ; 285: 91-98, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203897

RESUMO

The Arabidopsis oligopeptide transporter AtOPT6 is membrane transport protein that mediated transport of glutathione in both the reduced (GSH) and oxidized (GSSG) forms. In this study, the role of AtOPT6 in glutathione distribution throughout the plant was investigated. We found that transgenic Arabidopsis overexpressing AtOPT6 under the control of a phloem-specific promoter of sucrose-proton symporter 2 (pSUC2), remarkably increased AtOPT6 transcript levels, ranging from 30- to 40-fold in shoots and 6- to 10-fold in roots, relative to the wild type. AtOPT6-overexpressing lines could elevate the foliar glutathione content; however, glutathione content in the phloem did not change. We observed that the ratio of shoot glutathione content to total glutathione content increased in AtOPT6-overexpressing lines, but not in transgenic Arabidopsis with elevated foliar GSH synthesis. These results indicate the possibility that loading and unloading of glutathione in phloem tissues are enhanced in AtOPT6-overexpressing lines under the control of pSUC2. The results of heavy metal analysis revealed that transgenic Arabidopsis overexpressing AtOPT6 under the control of pSUC2 could promote the transport of Zn into shoots as effectively as transgenic Arabidopsis with elevated foliar GSH synthesis, or wild-type plants with exogenous foliar application of GSH.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/metabolismo , Floema/metabolismo , Brotos de Planta/metabolismo , Simportadores/fisiologia , Zinco/metabolismo , Aminoácidos/metabolismo , Glutationa/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
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