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1.
Life Sci ; 250: 117554, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32184123

RESUMO

BACKGROUND: Mental stress (MS) is related to endothelial dysfunction in overweight/obese men. It is believed that the pro-oxidant profile, associated with an imbalance in the vascular remodeling process, may contribute to deleterious effects of MS on endothelial function. However, it is unknown whether administration of ascorbic acid (AA), a potent antioxidant, can prevent oxidative and remodeling dysfunction during MS in these subjects. METHODS: Fourteen overweight/obese grade I men (27 ± 7 years; 29.7 ± 2.6 kg·m-2) underwent the Stroop Color Word Test for 5 min to induce MS after AA (3 g) or placebo (PL, 0.9% NaCl) intravenous infusions. Venous blood samples were collected at baseline and the last minute of MS to measure nitrite concentration (chemiluminescence), protein carbonylation, thiobarbituric acid reactive substances (TBARS) and catalase activity (colorimetric assays), superoxide dismutase (SOD; immunoenzymatic assay), activities of active/inactive (pro) forms of metalloproteinases-9 and -2 (MMP; zymography) and its respective tissue inhibitors concentration (TIMP-1 and TIMP-2; immunoenzymatic assays). RESULTS: At baseline, MMP-9 activity (p < 0.01), the MMP-9/proMMP-9 ratio (p = 0.02) and TIMP-1 concentration (p = 0.05) were reduced, whereas proMPP-9 activity was increased (p = 0.02) after AA compared to PL infusion. After PL infusion, MS increased protein carbonylation (p < 0.01), catalase (p < 0.01), and the MMP-9/proMMP-9 ratio (p = 0.04) when compared to baseline. AA infusion reduced protein carbonylation (p = 0.02), MMP-9 activity (p < 0.01), and MMP-9/pro-MMP-9 ratio (p < 0.01), while SOD (p = 0.04 vs baseline), proMPP-9 (p < 0.01 vs PL), MMP-2 (p < 0.01 vs PL) and TIMP-2 (p = 0.02 vs baseline) remained elevated during MS. CONCLUSIONS: AA appears to minimize the oxidative imbalance and vascular remodeling induced by MS.


Assuntos
Ácido Ascórbico/farmacologia , Obesidade/psicologia , Sobrepeso/psicologia , Estresse Psicológico , Remodelação Vascular/efeitos dos fármacos , Adulto , Antioxidantes/metabolismo , Catalase/metabolismo , Estudos Cross-Over , Endotélio Vascular/patologia , Humanos , Luminescência , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Oxidantes/metabolismo , Carbonilação Proteica , Fatores de Risco , Teste de Stroop , Superóxido Dismutase/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Adulto Jovem
2.
Food Chem Toxicol ; 135: 111038, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31825855

RESUMO

The aim of the study was to evaluate the potential protective role of sildenafil and tadalafil in contrast-induced nephropathy (CIN) by modulating oxidative stress. Thirty Wistar male rats were equally assigned into five groups: sham, CIN, CIN + sildenafil (10 mg/kg bw/day), CIN + tadalafil (5 mg/kg bw/day) and CIN + N-Acetyl Cysteine (NAC) (100 mg/kg bw/day) as a positive control. CIN was induced by 12 h dehydration and administration of indomethacin (10 mg/kg bw), N-ω- nitro-L-arginine methyl ester (10 mg/kg bw), and iopromide (3 g/kg bw iodine). Blood was drawn prior to and 24 h after CIN induction for evaluating renal function and oxidative stress. In the CIN group, total antioxidant capacity (TAC), reduced glutathione (GSH) and catalase (CAT) levels were significantly decreased; and protein carbonyl (PROTC) and thiobarbituric reactive species (TBARS) were significantly increased compared to the sham group. Pre- Sildenafil and tadalafil pre-treatment reduced CIN risk and reversed oxidative stress almost to the sham group levels. These results suggest that PDE5Is can be good candidates for preventing CIN based on their ability to modulate the oxidant/antioxidant balance.


Assuntos
Antioxidantes/metabolismo , Meios de Contraste/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Oxidantes/metabolismo , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Tadalafila/farmacologia , Acetilcisteína/administração & dosagem , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Nefropatias/enzimologia , Nefropatias/metabolismo , Masculino , Camundongos , Estresse Oxidativo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
3.
J Dairy Sci ; 103(1): 352-367, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733858

RESUMO

Our objective was to evaluate the effects of diet starch concentration and starch fermentability on inflammatory response markers and oxidant status during the early postpartum (PP) period and its carryover effects. Fifty-two multiparous Holstein cows were used in a completely randomized block design experiment with a 2 × 2 factorial arrangement of treatments. Treatments were starch concentration and starch fermentability of diets; diets were formulated to 22% (low starch, LS) or 28% (high starch, HS) starch with dry-ground corn (DGC) or high-moisture corn (HMC) as the primary starch source. Treatments were fed from 1 to 23 d PP and then switched to a common diet until 72 d PP to measure carryover (CO) effects. Treatment period (TP) diets were formulated to 22% forage neutral detergent fiber and 17% crude protein. The diet for the CO period was formulated to 20% forage neutral detergent fiber, 17% crude protein, and 29% starch. Coccygeal blood was collected once a week during the TP and every second week during the CO period. Liver and adipose tissue biopsies were performed within 2 d PP and at 20 ± 3 d PP. Blood plasma was analyzed for concentrations of albumin, haptoglobin, reactive oxygen and nitrogen species (RONS), and antioxidant potential (AOP), with lipopolysaccharide-binding protein (LBP) and TNFα evaluated during the TP only. Oxidative stress index (OSi) was calculated as RONS/AOP. Abundance of mRNA from genes involved in inflammation and glucose metabolism in liver and genes involved in lipogenesis in adipose tissue were determined. Data were analyzed separately for the TP and CO periods. During the TP, treatments interacted to affect concentrations of TNFα, haptoglobin, and LBP, with HMC increasing their concentrations for HS (9.38 vs. 7.45 pg/mL, 0.45 vs. 0.37 mg/mL, and 5.94 vs. 4.48 µg/mL, respectively) and decreasing their concentrations for LS (4.76 vs. 12.9 pg/mL, 0.27 vs. 0.41 mg/mL, and 4.30 vs. 5.87 µg/mL, respectively) compared with DGC. Effects of treatments diminished over time for LBP and haptoglobin with no differences by the end of the TP and no main CO effects of treatment for haptoglobin. The opposite treatment interaction was observed for albumin, with HMC tending to decrease its concentration for HS (3.24 vs. 3.34 g/dL) and increase its concentration for LS (3.35 vs. 3.29 g/dL) compared with DGC, with no carryover effect. Feeding DGC increased the OSi during the first week of the TP compared with HMC, with this effect diminishing over time; during the CO period HMC increased OSi for HS and decreased it for LS compared with DGC, with this effect diminishing toward the end of CO. Feeding HMC increased the abundance of genes associated with inflammation and gluconeogenesis in liver for HS and decreased it for LS compared with DGC. Feeding HS increased the mRNA abundance of genes associated with adipose tissue lipogenesis compared with LS. Results during the TP suggest that feeding LS-DGC and HS-HMC elicited a more pronounced inflammatory response and induced an upregulation of genes associated with inflammation and gluconeogenesis in liver, without effects on OSi, but effects on plasma markers of inflammation diminished during the CO period.


Assuntos
Bovinos/fisiologia , Dieta/veterinária , Carboidratos da Dieta/administração & dosagem , Lactação , Período Pós-Parto , Amido/administração & dosagem , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Antioxidantes/metabolismo , Reatores Biológicos/veterinária , Bovinos/metabolismo , Carboidratos da Dieta/metabolismo , Fibras na Dieta/metabolismo , Feminino , Fermentação , Humanos , Leite/metabolismo , Oxidantes/metabolismo , Amido/metabolismo
4.
Horm Mol Biol Clin Investig ; 39(3)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483756

RESUMO

Background Modulatory effects of soy extract and estradiol on the central nervous system (CNS) have been reported. The effect of soy on scopolamine-induced spatial learning and memory in comparison to the effect of estradiol was investigated. Materials and methods Ovariectomized rats were divided into the following groups: (1) control, (2) scopolamine (Sco), (3) scopolamine-soy 20 (Sco-S 20), (4) scopolamine-soy 60 (Sco-S 60), (5) scopolamine-estradiol 20 (Sco-E 20) and (6) scopolamine-estradiol 60 (Sco-E 60). Soy extract, estradiol and vehicle were administered daily for 6 weeks before training in the Morris water maze (MWM) test. Scopolamine (2 mg/kg) was injected 30 min before training in the MWM test. Results In the MWM, the escape latency and traveled path to find the platform in the Sco group was prolonged compared to the control group (p < 0.001). Treatment by higher doses of soy improved performances of the rats in the MWM (p < 0.05 - p < 0.001). However, treatment with both doses of estradiol (20 and 60 µg/kg) resulted in a statistically significant improvement in the MWM (p < 0.01 - p < 0.001). Cortical, hippocampal and serum levels of malondialdehyde (MDA), as an index of lipid peroxidation, were increased which was prevented by soy extract and estradiol (p < 0.001). Cortical, hippocampal as well as serum levels of the total thiol, superoxide dismutase (SOD) and catalase (CAT) in Sco group were lower than the control group (p < 0.001) while they were enhanced when the animals were treated by soy extract and estradiol (p < 0.01 - p < 0.001). Conclusions It was observed that both soy extract and estradiol prevented learning and memory impairments induced by scopolamine in ovariectomized rats. These effects can be attributed to their protective effects on oxidative damage of the brain tissue.


Assuntos
Estradiol/farmacologia , Transtornos da Memória/etiologia , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Escopolamina/farmacologia , Soja/química , Aprendizagem Espacial/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Biomarcadores , Catalase/metabolismo , Feminino , Aprendizagem em Labirinto , Transtornos da Memória/tratamento farmacológico , Ovariectomia , Oxidantes/metabolismo , Estresse Oxidativo , Extratos Vegetais/química , Ratos , Superóxido Dismutase/metabolismo
5.
Nature ; 572(7768): 249-253, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31367038

RESUMO

Both single and multicellular organisms depend on anti-stress mechanisms that enable them to deal with sudden changes in the environment, including exposure to heat and oxidants. Central to the stress response are dynamic changes in metabolism, such as the transition from the glycolysis to the pentose phosphate pathway-a conserved first-line response to oxidative insults1,2. Here we report a second metabolic adaptation that protects microbial cells in stress situations. The role of the yeast polyamine transporter Tpo1p3-5 in maintaining oxidant resistance is unknown6. However, a proteomic time-course experiment suggests a link to lysine metabolism. We reveal a connection between polyamine and lysine metabolism during stress situations, in the form of a promiscuous enzymatic reaction in which the first enzyme of the polyamine pathway, Spe1p, decarboxylates lysine and forms an alternative polyamine, cadaverine. The reaction proceeds in the presence of extracellular lysine, which is taken up by cells to reach concentrations up to one hundred times higher than those required for growth. Such extensive harvest is not observed for the other amino acids, is dependent on the polyamine pathway and triggers a reprogramming of redox metabolism. As a result, NADPH-which would otherwise be required for lysine biosynthesis-is channelled into glutathione metabolism, leading to a large increase in glutathione concentrations, lower levels of reactive oxygen species and increased oxidant tolerance. Our results show that nutrient uptake occurs not only to enable cell growth, but when the nutrient availability is favourable it also enables cells to reconfigure their metabolism to preventatively mount stress protection.


Assuntos
Antioxidantes/metabolismo , Lisina/metabolismo , Poliaminas/metabolismo , Saccharomyces cerevisiae/metabolismo , Antiporters/metabolismo , Cadaverina/metabolismo , Glutamina/metabolismo , Glutationa/metabolismo , NADP/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ornitina Descarboxilase/metabolismo , Oxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
6.
Life Sci ; 233: 116704, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31369761

RESUMO

AIMS: Doxorubicin, an anticancer drug, has a toxic effect on many tissues such as heart, pancreas, liver, kidney, and testis. The aim of current study is to investigate whether melatonin would be protective in doxorubicin-induced beta (ß) cell toxicity via HMGB1/TLR2/TLR4/MAPK/NF-қB signaling pathway. MAIN METHODS: Human pancreatic ß cell (1.1B4) was used in the present study. Four experimental groups were created as control, melatonin (10 µM), doxorubicin (2 µM) and the combination of melatonin with doxorubicin. Following 24-h treatment, Mitogen-activated protein kinase (MAPKs), Toll like receptors (TLRs) including TLR2 and TLR4, pro-and anti-apoptotic protein expression levels were determined by western blotting. Total antioxidant (TAS), oxidant status (TOS) and oxidative stress index (OSI) of the cells as well as superoxide dismutase (SOD) levels were determined. Active caspase-8 activity was measured and TUNEL staining was performed to study apoptotic pathways. Mitochondrial membrane potential (MMP), some protein expressions and F-actin distribution were analyzed. KEY FINDINGS: Doxorubicin caused to depolarize MMP, resulting in enhancing apoptosis by activation of caspase-8 via MAPKs/NF-кB pathway via elevation of TOS and decreasing TAS. Also, doxorubicin destroyed F-actin distribution and elevated TLR2 and some apoptotic proteins, including Bax. However, co-treatment of melatonin with doxorubicin could reverse depolarization of MMP and inhibition of apoptosis through MAPK/NF-кB signaling by decreasing TOS and increasing TAS. The co-treatment reversed the alternations of TLR2, TLR4, MAPKs and apoptotic protein expressions induced by doxorubicin. SIGNIFICANCE: Melatonin could be a good candidate against pancreatic ß cell toxicity-induced by doxorubicin through TLR2/TLR4/MAPK/NF-кB pathways.


Assuntos
Doxorrubicina/efeitos adversos , Células Secretoras de Insulina/efeitos dos fármacos , Melatonina/farmacologia , Substâncias Protetoras/farmacologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Antibióticos Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Células Cultivadas , Proteína HMGB1/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/metabolismo , Oxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Oxid Med Cell Longev ; 2019: 1965364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396298

RESUMO

Background and Aim: Exercise is an effective strategy to reduce obesity-induced oxidative stress. The purpose of this study was to compare the effects of two training modalities (moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT)) on the pro/antioxidant status of different tissues in obese Zucker rats. Methods: Eight-week-old male Zucker rats (fa/fa, n = 36) were subdivided in three groups: MICT, HIIT, and control (no exercise) groups. Trained animals ran on a treadmill (0° slope), 5 days/week for 10 weeks (MICT: 51 min at 12 m·min-1; HIIT: 6 sets of 3 min at 10 m·min-1 followed by 4 min at 18 m·min-1). Epididymal (visceral) and subcutaneous adipose tissue, gastrocnemius muscle, and plasma samples were collected to measure oxidative stress markers (advanced oxidation protein products (AOPP), oxidized low-density lipoprotein (oxLDL)), antioxidant system markers (ferric-reducing ability of plasma (FRAP), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities), and prooxidant enzymes (NADPH oxidase and xanthine oxidase (XO) activities, myeloperoxidase content). Results: Compared with the control, MICT increased GPx and catalase activities and the FRAP level in epididymal adipose tissue. HIIT increased the AOPP level in subcutaneous adipose tissue. In the muscle, HIIT increased both SOD and GPx activities and reduced the AOPP level, whereas MICT increased only SOD activity. Finally, plasma myeloperoxidase content was similarly decreased by both training modalities, whereas oxLDL was reduced only in the MICT group. Conclusion: Both HIIT and MICT improved the pro/antioxidant status. However, HIIT was more efficient than MICT in the skeletal muscle, whereas MICT was more efficient in epididymal adipose tissue. This suggests that oxidative stress responses to HIIT and MICT are tissue-specific. This could result in ROS generation via different pathways in these tissues. From a practical point of view, the two training modalities should be combined to obtain a global response in people with obesity.


Assuntos
Tecido Adiposo/metabolismo , Músculo Esquelético/metabolismo , Estresse Oxidativo , Condicionamento Físico Animal , Animais , Antioxidantes/metabolismo , Glutationa Peroxidase/metabolismo , Treinamento Intervalado de Alta Intensidade , Lipoproteínas LDL/sangue , Masculino , Malondialdeído/sangue , NADPH Oxidases/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Oxidantes/metabolismo , Ratos , Ratos Zucker , Superóxido Dismutase/metabolismo
8.
Chemosphere ; 237: 124501, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31398612

RESUMO

Several evidences from the literature showed that the coexistence of nickel and zinc in polluted waters is related to the similarity in their geogenic and anthropogenic factors. Although most environmental exposures to metals do not occur singly, there is a paucity of scientific knowledge on the effects of zinc and nickel co-exposure on mammalian reproductive health. The present study investigated the influence of co-exposure to nickel and zinc on male reproductive function in rats. Experimental rats were co-exposed to environmentally relevant concentrations of waterborne nickel (75 and 150 µg NiCl2 L-1) and zinc (100 and 200 µg ZnCl2 L-1) for 45 successive days. Subsequently, reproductive hormones were assayed whereas the hypothalamus, epididymis and testes of the rats were processed for the assessment of oxidative stress and inflammation indices, caspase-3 activity and histology. Results indicated that co-exposure to nickel and zinc significantly (p < 0.05) abolished nickel-mediated diminution of antioxidant defense mechanisms while diminishing levels of reactive oxygen and nitrogen species and lipid peroxidation in the hypothalamus, epididymis and testes of the exposed rats. Additionally, co-exposure to zinc abated nickel-mediated diminutions in luteinizing hormone, follicle-stimulating hormone, serum and intra-testicular testosterone with concomitant enhancement of sperm production and quality. Further, zinc abrogated nickel-mediated elevation in inflammatory biomarkers including nitric oxide, tumor necrosis factor alpha, interleukin-1 beta as well as caspase-3 activity. The protective influence of zinc on nicked-induced reproductive toxicity was well supported by histological data. Overall, zinc ameliorated nickel-induced reproductive dysfunction via its anti-oxidant, anti-inflammatory, anti-apoptotic and spermato-protective activities in rats.


Assuntos
Níquel/toxicidade , Poluentes Químicos da Água/toxicidade , Zinco/toxicidade , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Epididimo/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Hormônio Luteinizante/sangue , Masculino , Oxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Reprodução/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/sangue
9.
Redox Biol ; 26: 101296, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31465957

RESUMO

Organisms have evolved two different classes of the ubiquitous enzyme fumarase: the [4Fe-4S] cluster-containing class I enzymes are oxidant-sensitive, whereas the class II enzymes are iron-free and therefore oxidant-resistant. When hydrogen peroxide (H2O2) attacks the most-studied [4Fe-4S] fumarases, only the cluster is damaged, and thus the cell can rapidly repair the enzyme. However, this study shows that when elevated levels of H2O2 oxidized the class I fumarase of the obligate anaerobe Bacteroides thetaiotaomicron (Bt-Fum), a hydroxyl-like radical species was produced that caused irreversible covalent damage to the polypeptide. Unlike the fumarase of oxygen-tolerant bacteria, Bt-Fum lacks a key cysteine residue in the typical "CXnCX2C″ motif that ligands [4Fe-4S] clusters. Consequently H2O2 can access and oxidize an iron atom other than the catalytic one in its cluster. Phylogenetic analysis showed that certain clades of bacteria may have evolved the full "CXnCX2C″ motif to shield the [4Fe-4S] cluster of fumarase. This effect was reproduced by the construction of a chimeric enzyme. These data demonstrate the irreversible oxidation of Fe-S cluster enzymes and may recapitulate evolutionary steps that occurred when microorganisms originally confronted oxidizing environments. It is also suggested that, if H2O2 is generated within the colon as a consequence of inflammation or the action of lactic acid bacteria, the inactivation of fumarase could potentially impair the central fermentation pathway of Bacteroides species and contribute to gut dysbiosis.


Assuntos
Fumarato Hidratase/química , Fumarato Hidratase/metabolismo , Peróxido de Hidrogênio/metabolismo , Ferro/química , Estresse Oxidativo/efeitos dos fármacos , Enxofre/química , Motivos de Aminoácidos , Sítios de Ligação , Catálise , Ativação Enzimática , Peróxido de Hidrogênio/química , Ferro/metabolismo , Ligantes , Modelos Moleculares , Oxidantes/química , Oxidantes/metabolismo , Filogenia , Ligação Proteica , Relação Estrutura-Atividade , Enxofre/metabolismo
10.
Am J Chin Med ; 47(5): 1043-1056, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31311299

RESUMO

Baicalein is a natural flavonoid with anti-oxidant activities protecting against ischemia/reperfusion (I/R) injury. Previous studies suggest that oxidative burst early after reperfusion accelerates cell death. We therefore investigated the critical therapeutic window of baicalein by examining the timing of baicalein treatment in relation to its oxidant modulating and cytoprotective effects. Using an established chick cardiomyocyte model of I/R, we administered baicalein at various time points after reperfusion and assessed cell viability and the profiles of reactive oxygen species (ROS), nitric oxide (NO), and Akt phosphorylation. Baicalein administered at the onset of reperfusion resulted in a concentration-dependent reduction of cell death (25 µM 48.2±1.9%, 50µM 43.8±1.5%, 100µM 36.6±2.1%, vs. I/R control 57.3±1.4%, all p<0.05). Baicalein (100µM) timely and effectively scavenged ROS burst and enhanced NO production in the early reperfusion phase. Cotreatment with NO synthase (NOS) inhibitor l-NAME (200µM) partially abrogated the cytoprotective effect. Baicalein (100µM) given after reperfusion lost protective effect in a time-dependent manner with cytoprotection completely lost if >60min. Even with only 15-min delay after reperfusion, the ROS scavenging effect was abolished and the NO enhancing effect markedly reduced. The phosphorylation of Akt, an upstream regulator of eNOS, also diminished as the delay lengthened. In conclusion, baicalein treatment after reperfusion confers cardioprotection in a concentration- and time-dependent manner. The critical therapeutic window lies in the early reperfusion phase, during which ROS scavenging and Akt-eNOS mediated NO signaling are most effective.


Assuntos
Cardiotônicos/farmacologia , Flavanonas/farmacologia , Depuradores de Radicais Livres/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Óxido Nítrico/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Células Cultivadas , Galinhas , Humanos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/genética , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Oxidantes/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
11.
Gene ; 712: 143966, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31279711

RESUMO

BACKGROUND: Acute paracetamol (PCM) toxicity is a clinical problem; can result in a serious liver injury that finally may progress to acute liver failure. Curcumin (CUR) is a prevalent natural compound that can maintain prooxidant/antioxidant balance and thus can help in liver protection; also, Silymarin (SL) is a traditional antioxidant herb, used to treat liver disorders through scavenging free radicals. This study aimed to illustrate the histological, biochemical and molecular changes induced by acute PCM overdose on rats' liver to elucidate the effectiveness of CUR compared to SL in alleviating such changes. MATERIALS AND METHODS: Male Wister Albino rats were divided into 6 groups each comprising 23 rats: control group, curcumin (CUR) treated group received (100 mg CUR/ kg), silymarin treated group received (100 mg SL/kg) for 7 successive days. Paracetamol (PCM) exposed group administered a single dose of PCM (200 mg/kg orally on 8th day). PCM + CUR group and PCM + SL group pretreated with CUR and SL respectively for 7 days then received single PCM dose (200 mg/kg) on the 8th day. Blood and liver tissues were collected for biochemical, histopathological and immunohistochemical analyses using anti-p53 antibody. In addition, real time polymerase chain reaction (RT- PCR) was used to measure Bax, bcl2 and Peroxisome proliferator-activated receptor-gamma (PPAR γ) mRNA expression levels. RESULTS: In the paracetamol overdose group, the liver architecture showed necrotic changes, hydropic degeneration, congestion and dilatation of central veins. This hepatocellular damage was confirmed by a significant increase of AST, ALT levels and by an apparent increase in the number of p53 stained cells. PCM toxicity showed significant elevation of total oxidant status (TOS), oxidant status index (OSI) and decreased total antioxidant capacity (TAC) compared to controls (p < 0.001). Gene expression analysis showed that PCM caused an elevation of bcl2 and a reduction of both Bax and PPARγ mRNA expression. The histological alternation in the liver architecture was markedly improved in (PCM + CUR) group compared to (PCM+ SL) group, with an obvious decrease in the number of P53 stained cells. CUR pretreatment inhibited the elevation of TOS and OSI as well as the reduction of TAC caused by PCM toxicity compared to (PCM + SL) group. CONCLUSION: Both SL and CUR pretreatment prevented the toxic effects of PCM, but CUR is more effective than SL in ameliorating acute PCM induced hepatotoxicity.


Assuntos
Acetaminofen/toxicidade , Curcumina/farmacologia , Falência Hepática Aguda/induzido quimicamente , Fígado/efeitos dos fármacos , Silimarina/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Apoptose , Sinergismo Farmacológico , Imuno-Histoquímica , Masculino , Oxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Proteína X Associada a bcl-2/metabolismo
12.
Aquat Toxicol ; 213: 105228, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229888

RESUMO

The present work was conducted to study how restoration of perturbed oxidant and antioxidant homeostasis is achieved in the UV-C radiation exposed cells of cyanobacterium Nostoc muscorum Meg1. Exposure to varying doses of UV-C radiation (6, 12, 18 and 24 mJ/cm2) showed damage to ultrastructures especially cytoplasmic membrane, cell wall and organisation of thylakoid membranes of the cyanobacterium under transmission electron microscope (TEM). All doses of UV-C exposure significantly induced most of the enzymatic antioxidant {catalase, superoxide dismutase (SOD) and glutathione reductase (GR)} activities, their protein levels (western blot analysis) and mRNA levels (real time PCR analysis) within the first hour of post UV-C radiation incubation period. In the same way, contents of many non-enzymatic antioxidants such as ascorbic acid, reduced glutathione, proline, phenol and flavonoids were also augmented in response to such UV-C radiation exposure. Although notable increase in ROS level was only seen in cultures treated with 24 mJ/cm2 UV-C exposure which also registered increase in protein oxidation (22%) and lipid peroxidation (20%), this boost in both enzymatic and non-enzymatic antioxidants was significant in all radiation exposed cells indicating cell's preparation to combat rise in oxidants. Further, albeit all antioxidants increased considerably, their levels were restored back to control values by day seventh re-establishing physiological redox state for normal metabolic function. The combined efficiency of the enzymatic and non-enzymatic antioxidants were so effective that they were able to bring down the increase levels of ROS, lipid peroxidation and protein oxidation to the physiological levels within 1 h of radiation exposure signifying their importance in the defensive roles in protecting the organism from oxidative toxicity induced by UV-C radiation exposure.


Assuntos
Antioxidantes/metabolismo , Homeostase , Nostoc muscorum/fisiologia , Nostoc muscorum/efeitos da radiação , Oxidantes/metabolismo , Estresse Fisiológico/efeitos da radiação , Raios Ultravioleta , Ácido Ascórbico/metabolismo , Catalase/metabolismo , Cisteína/metabolismo , Flavonoides/metabolismo , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Nostoc muscorum/ultraestrutura , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Prolina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/toxicidade
13.
J Immunol ; 202(11): 3127-3134, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31109945

RESUMO

The phagocyte NADPH oxidase is responsible for the neutrophil's great capacity to produce reactive oxygen species (ROS). The NADPH oxidase can be assembled in the plasma membrane, as well as in membranes of intracellular vesicles, giving neutrophils the ability to direct ROS production to distinct subcellular sites. Neutrophil ROS contribute to microbial killing, trigger formation of neutrophil extracellular traps and appear to partake in inflammation control. Consequently, function-disrupting mutations in the NADPH oxidase lead to chronic granulomatous disease, characterized by severe infections and inflammatory disorders. Recent experimental data and description of a novel chronic granulomatous disease subtype (p40phox-deficiency) imply that ROS generated in intracellular compartments are key for NETosis and for controlling inflammatory signaling. We foresee boosted interest in intracellular ROS production. To fully understand where and how such ROS function, however, limitations of assay systems to measure ROS need to be appreciated, and the development of novel techniques/reagents would be highly useful.


Assuntos
Armadilhas Extracelulares/fisiologia , Espaço Intracelular/metabolismo , NADPH Oxidases/metabolismo , Neutrófilos/fisiologia , Oxidantes/metabolismo , Animais , Doença Granulomatosa Crônica/genética , Humanos , Mutação/genética , NADPH Oxidases/genética , Oxirredução , Estresse Oxidativo/imunologia , Fagocitose , Fosfoproteínas/genética , Espécies Reativas de Oxigênio/metabolismo
14.
Redox Biol ; 24: 101180, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31022672

RESUMO

In the present study, we show that cholesterol crystals induce NFκB activation, and ICAM1 and VCAM1 expression via xanthine oxidase-mediated H2O2 production and PP2A inhibition in influencing endothelial cell and monocyte interactions and all these adverse effects of cholesterol crystals could be attenuated by proresolving lipid mediator RvD1. In addition, feeding mice with cholesterol rich diet (CRD) increased xanthine oxidase expression, its activity and H2O2 production leading to PP2A inhibition, NFκB activation, and ICAM1 and VCAM1 expression and RvD1 attenuated all these effects of CRD substantially. Furthermore, peripheral blood mononuclear cells (PBMCs) from wild type mice when injected into mice that were fed with CRD or RvD1 + CRD showed increased leukocyte trafficking to arteries of CRD-fed mice as compared to RvD1 + CRD mice. These findings suggest that cholesterol crystals via promoting oxidant stress and inhibiting Ser/Thr phosphatases such as PP2A stimulate NFκB activation and ICAM1 and VCAM1 expression, and thereby enhance EC-monocyte interactions. In addition, proresolving lipid mediators such as RvD1 appear to exert their anti-inflammatory effects via countering the adverse effects of cholesterol crystals or CRD.


Assuntos
Colesterol/metabolismo , Células Endoteliais/metabolismo , Peróxido de Hidrogênio/farmacologia , Molécula 1 de Adesão Intercelular/metabolismo , Monócitos/metabolismo , NF-kappa B/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Colesterol/química , Ácidos Docosa-Hexaenoicos/farmacologia , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Camundongos , Oxidantes/metabolismo
15.
Curr Microbiol ; 76(6): 698-705, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30955044

RESUMO

Group A streptococcus (GAS) is an important human pathogen whose clinical isolates differ in their ability to produce hydrogen peroxide (H2O2). H2O2 is primarily produced by the enzyme lactate oxidase (LctO), an in depth in silico research revealed that all genome-sequenced GAS possess the required gene lctO. The importance of lctO for GAS is underlined by its highly conserved catabolite control element (cre box) as well as its perfect promotor sequence in comparison to the known consensus sequences of the Gram-positive model organism Bacillus subtilis. In this study, we provide further insight in the function and regulation of lactate oxidase by analyzing a large group of clinical GAS isolates. We found that H2O2 production increased over time in the late stationary phase; after 4 days of incubation, 5.4% of the isolates showed a positive result at 37 °C, while the rate increased to 16.4% at 20 °C. This correlation between H2O2 production and low temperatures suggests additional regulatory mechanisms for lctO besides catabolite control protein A (CcpA) and indicates that lctO might play a role for GAS energy metabolism at sub-body temperatures. Furthermore, we could identify that H2O2 production was different among clinical isolates; we could correlate H2O2 production to emm-types, indicating that emm-types 6 and 75 had the highest rate of H2O2 production. The emm-type- and temperature-dependent H2O2 production of clinical GAS isolates might contribute to their different survival strategies.


Assuntos
Antígenos de Bactérias/análise , Proteínas da Membrana Bacteriana Externa/análise , Proteínas de Transporte/análise , Peróxido de Hidrogênio/metabolismo , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Oxidantes/metabolismo , Streptococcus pyogenes/metabolismo , Streptococcus pyogenes/efeitos da radiação , Proteínas de Bactérias/metabolismo , Metabolismo Energético , Regulação Bacteriana da Expressão Gênica , Humanos , Proteínas Repressoras/metabolismo , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/classificação , Streptococcus pyogenes/genética , Temperatura
16.
J Biosci Bioeng ; 128(3): 337-343, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30956102

RESUMO

Enzymatic cycling system (coupled dehydrogenase-catalyzed biosystem being composed of two elementary enzymatic reactions mediated by NAD(P)H + NAD(P)+) is industrially attractive for reducing prochiral carbonyl compounds to the corresponding chiral hydroxyl compounds. The reaction rate equation of the batch-wise biosystem was generally derived by ordered Bi Bi mechanism of two-substrate enzyme reaction on several reasonable assumptions. The rate equations of the batch-wise biosystem was generalized by transforming them into the dimensionless forms. The dimensionless forms were solved numerically. It was revealed that the batch-wise biosystem was generally made up of unique 3 phases, i.e., phases I, II and III. Phase I was very short transient so that the biosystem entered rapidly phase II. In phase II the consumption rate dynamically balanced with its formation rate so that the concentration of NAD(P)H was invariable with time (and hence NAD(P)+ concentration was, too). Phase III was substrate-exhausting phase, and the coenzyme concentration became finally only [NAD(P)+] or only [NAD(P)H] depending on the initial molar ratio of the prochiral carbonyl compound to the substrate of the coenzyme regeneration reaction ( [Formula: see text] ) > or <1.0. In phases I and II the numerically calculated values of state variables were very close to the analytical but approximate ones. Preferable initial conditions of the batch-wise enzymatic cycling system, i.e., the initial coenzyme species = NAD(P)+ and [Formula: see text] , were proposed. As the main assumption irreversibility of the two elemental enzymatic reactions was discussed. Validity of the proposed rate equations was mentioned.


Assuntos
Biocatálise , Radical Hidroxila/metabolismo , Engenharia Metabólica/métodos , NADP/metabolismo , NAD/metabolismo , Oxidantes/metabolismo , Oxirredutases/metabolismo , Técnicas de Cultura Celular por Lotes/métodos , Reatores Biológicos/microbiologia , Coenzimas/metabolismo , Ativação Enzimática , Reutilização de Equipamento , Radical Hidroxila/química , Cinética , Modelos Teóricos , Oxidantes/química , Estereoisomerismo
17.
PLoS One ; 14(4): e0215540, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30998725

RESUMO

The phenolic composition and content of olive fruit are some of the attributes that determine oil quality. This composition depends on the olive variety, the cultivation system, and the fruit's ripeness. This study considered two olive varieties (Manzanilla and Morisca), under two water regimes (irrigated and rainfed), harvested at three stages of maturation (S1, S2, and S3), over three consecutive campaigns (2011, 2012, and 2013). The accumulation of phenols in the fruit was found to depend only on the stage of ripeness, while the flavonoid and phenylpropanoid contents depended also on the variety and the water regime. Superoxide dismutase (SOD) activity was linked to O2- production, which in turn depended on water regime, variety, and stage of maturation (this last being a process involving ROS). The peroxidase (POX) activity seemed only to depend on ripeness, while polyphenol oxidase (PPO) activity varied from year to year as well as presenting a strong ripeness dependence that was in clear coherence with the levels of phenolic compounds that the olives accumulate. All these relationships between the variables and the factors conform a dataset with the structure of a multidimensional array that is difficult to interpret using conventional techniques of statistical analysis. This work takes a novel approach (MultiDimensional Scaling associated with a Partial Triadic Analysis, MDS-PTA) to the analysis of this type of data structure which allows its correct interpretation. The analysis showed that the state of maturation of the olives is the most clearly discriminating factor, far more so than the cultivar, water regime, or year. Thus, the phenols and the total antioxidant activity (FRAP) showed strong clustering, being closely related in all three years studied. The oxidant and antioxidant activities showed a certain tendency to cluster, although in these cases the year also had an influence as a factor, indicating that these parameters depend more on external factors and less on ripeness.


Assuntos
Antioxidantes/metabolismo , Frutas/crescimento & desenvolvimento , Olea/crescimento & desenvolvimento , Oxidantes/metabolismo , Catecol Oxidase/metabolismo , Flavonoides/metabolismo , Peroxidase/metabolismo , Proteínas de Plantas/metabolismo
18.
Oxid Med Cell Longev ; 2019: 4619865, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984336

RESUMO

Numerous studies have reported a strong association between increased production of reactive oxygen species (ROS) and the pathobiology of several diseases, and cancer in particular. Therefore, manipulation of cellular oxidative stress levels represents an important therapeutic target. Recently, resveratrol (RESV), a naturally occurring phytochemical, has been shown to sensitize several cell lines to the anticancer effects of other chemotherapeutic agents, including paclitaxel (PAX). However, the molecular mechanisms of action of RESV through oxidative sensitive TRPM2 channel activation remain unclear. The aim of this study was to evaluate the effect of combination therapy of RESV and PAX on activation of TRPM2 in DBTRG glioblastoma cells. DBTRG cells were divided into four treatment groups: control, RESV (50 µM), PAX (50 µM), and PAX + RESV for 24 hours. Our data shows that markers for apoptosis, mitochondrial membrane depolarization and mitochondrial function, intracellular steady-state ROS levels, caspase 3 activity, TRPM2 current density, and Ca2+ florescence intensity were significantly increased in DBTRG cells following treatment with PAX and RESV, respectively, although cell viability was also decreased by these treatments. These biochemical markers were further increased to favor the anticancer effects of PAX in DBTRG cells in combination with RESV. The PAX and RESV-mediated increase in current density and Ca2+ florescence intensity was decreased with a TRPM2 blocker. This suggests that for this combination therapy to have a substantial effect on apoptosis and cell viability, the TRPM2 channel must be stimulated.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Oxidantes/metabolismo , Paclitaxel/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/uso terapêutico , Canais de Cátion TRPM/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Humanos , Paclitaxel/farmacologia , Resveratrol/farmacologia
19.
Arch Biochem Biophys ; 665: 132-142, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30872062

RESUMO

Oxidative stress is a major hallmark of cardiac ischemia/reperfusion (I/R) injury, which is in part due to the release of the enzyme myeloperoxidase (MPO) from activated infiltrating leukocytes, and the subsequent production of the oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). Although exposure of various cell types to either oxidant is known to cause cellular dysfunction within a variety of pathological settings, the precise role of HOCl and HOSCN in the initiation of tissue damage evident following cardiac I/R injury remains unclear. In this study, we have employed the use of the cardiac myoblast cell line H9c2 as a model for cardiac myocytes and demonstrate that exposure to either oxidant elicits a dose-dependent increase in cytosolic calcium accumulation, depletion of the cellular thiol pool, reduction of glutathione (GSH) levels and loss of mitochondrial inner trans-membrane potential, concomitant with increased necrotic cell death. H9c2 cell recovery from the initial oxidant exposure involves the initiation of cell survival signalling pathways centred around Nrf2-antioxidant response element (ARE) and activator protein 1 (AP-1) activation, with cell survival accompanied by restoration of mitochondrial function following exposure to HOSCN, but not HOCl. These data highlight the cellular responses elicited by HOCl and HOSCN in cardiac myocytes furthering our understanding of the pathogenesis of oxidant injury following cardiac I/R injury.


Assuntos
Mioblastos Cardíacos/metabolismo , Oxidantes/metabolismo , Peroxidase/metabolismo , Animais , Linhagem Celular , Glutationa/metabolismo , Ácido Hipocloroso/metabolismo , Estresse Oxidativo , Ratos , Transdução de Sinais , Tiocianatos/metabolismo
20.
Oxid Med Cell Longev ; 2019: 8472346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881599

RESUMO

The concentration of thiobarbituric acid reactive substances (TBARSs) in plasma and erythrocytes, the activity of selected antioxidant enzymes in erythrocytes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and the levels of hemoglobin (HGB) and haematocrit (HCT) were determined in 40 patients with sudden sensorineural hearing loss (SSNHL) subjected to 14 treatment sessions in a Haux Starmed 2200 hyperbaric chamber. Hyperbaric oxygen (HBO) therapy involved breathing 100% oxygen at 0.25 MPa. Blood for analysis was collected from the basilic vein at three time points: before the first HBO session, approximately 5 min after the first session, and after the 14th session. The control group included 20 healthy individuals never before treated with HBO therapy. Compared to the pre-HBO values, a 10% increase (P < 0.05) in the TBARS concentration in erythrocytes, a 28% increase in the GPx activity (P < 0.05), and a 7% decrease in the SOD activity (P < 0.05) were observed after 14 HBO sessions. The CAT activity decreased by 6% (P < 0.05) after the first session. The TBARS concentration in plasma was 13% higher (P < 0.01), while that in erythrocytes was 24% lower (P < 0.001) in the SSNHL patients before the first HBO session compared to the control group. The CAT activity in the SSNHL patients before HBO therapy was 26% higher (P < 0.001) than that in the control group. A statistically significant reduction in HGB and HCT after 14 HBO sessions (P < 0.01) compared to the pre-HBO values was demonstrated. SSNHL is accompanied by disturbance in the oxidant-antioxidant equilibrium. Repeated stimulation with hyperbaric oxygen modulates the activity of antioxidant enzymes. It seems that the increased generation of hydrogen peroxide is responsible for the changes in the activity of antioxidant barrier enzymes observed after HBO sessions.


Assuntos
Antioxidantes/metabolismo , Perda Auditiva Neurossensorial/terapia , Oxigenação Hiperbárica/métodos , Oxidantes/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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