RESUMO
Erectile dysfunction (ED) is an early manifestation of arteriosclerosis associated with endothelial damage/dysfunction and to a blunted ability of cultured mononuclear circulating cells (MNCs) to differentiate circulating angiogenic cells (CACs), putatively involved in endothelial damage repair. Here we explored effects of human serum (HS) from patients with ED and cardiovascular risk factors (VRFs) but no clinical atherosclerosis, on cultured MNCs of healthy men to differentiate CACs and to form colonies. Effect of HS on number of CACS and of colony forming units (CFUs) was correlated with circulating markers of endothelial damage and with angiogenic modulators. MNCs from healthy men were cultured in standard conditions or with 20% HS from 35 patients with ED and from 10 healthy men. CACs were identified after 7 days of culture by uptake of acetylated low-density lipoprotein with concomitant binding of Ulex europaeus agglutinin I. CFUs were counted after 5 days of culture. Enzyme-linked immunosorbent assays assessed plasmatic soluble (s) form of E-selectin, Endothelin (ET)-1, tissue type plasminogen activator (tPA), vascular endothelial growth factor (VEGF)(165) and sVEGF receptor (R)-1. The number of CACs and of CFUs from healthy men was reduced after culturing MNCs with HS compared to standard medium. The inhibitory effect was significantly higher with HS from ED patients with higher or lower VRF exposure compared to healthy men. Inhibition was positively correlated with VRFs exposure, with ED severity, with common carotid artery intima media thickness measured using B-mode ultrasound, and to a lesser extent with plasmatic sE-Selectin, sET-1 and sVEGFR-1. Dysfunction of cells involved in vascular homoeostasis is induced by soluble factors still unknown and already present in a very initial systemic vascular disease in men with ED and VRFs.
Assuntos
Doenças Cardiovasculares/etiologia , Disfunção Erétil/sangue , Leucócitos Mononucleares/efeitos dos fármacos , Adulto , Idoso , Espessura Intima-Media Carotídea , Selectina E/sangue , Endotelina-1/sangue , Endotélio Vascular/fisiopatologia , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Células-Tronco , Ativador de Plasminogênio Tecidual/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangueRESUMO
Intense exercise induces a pro-inflammatory status through a mechanism involving the NAD(P)H oxidase system. We focused our attention on p22phox, a subunit of the NAD(P)H oxidase, and on its allelic polymorphism C242T, which is known to affect the functional activity of the enzyme. We investigated whether the p22phox C242T variants exhibit systemic effects in healthy subjects by analyzing the proinflammatory and cardiocirculatory responses to physical exercise in endurance athletes. The group of study consisted of 97 long distance runners, 37 +/- 4.4 yrs of age, with similar training history. The subjects underwent a maximal stress test during which both inflammatory and cardiopulmonary parameters were monitored. Our results demonstrate that T allele deeply influences the neutrophil activation in response to intense exercise, since T carriers were characterized by significantly lower release of myeloperoxidase (MPO), a classical leukocyte derived pro-inflammatory cytokine. In addition, the presence of T allele was associated with a higher cardiopulmonary efficiency as evidenced by a significantly lower Heart Rate (HR) at the peak of exercise and, when a dominant model was assumed, by a higher maximal oxygen uptake (VO2 max). On the other hand, no effects of 242T mutation on the plasmatic total antioxidant capacity (TAC) and on the cortisol responses to the physical exercise were detected. In conclusion, our data support a systemic role for p22phox C242T polymorphism that, modifying the intensity of the inflammatory response, can influence the cardiovascular adaptations elicited by aerobic training. These results contribute to support the hypothesis of a systemic effect for the C242T polymorphism and of its possible functional rebound in healthy subjects.
Assuntos
Exercício Físico , Inflamação/etiologia , NADPH Oxidases/genética , Polimorfismo Genético , Adulto , Humanos , Hidrocortisona/sangue , Masculino , Estresse Oxidativo , Consumo de Oxigênio , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , CorridaRESUMO
Reactive oxygen species (ROS) production is known to increase as a result of muscular contractile activity and this phenomenon may perturb the fine-controlled cellular redox homeostasis within cells and tissues. We studied the possible correlations between individual aerobic performance-related factors and the oxidative stress markers profile in the serum of thirty-five endurance male runners that experienced a modified Bruce-based maximal graded exercise test. Our investigation assessed the systemic levels of malondialdehyde (MDA), protein carbonyl content (PCC) and total antioxidant status (TAS). We found that redox-related parameters and aerobic performance indicators were correlated. Indeed, significant negative associations between TAS and PCC (r-value -0.7, p<0.001) and between TAS and total protein content (r-value -0.4, p=0.005) were observed. A significant positive association between total protein and PCC (r-value 0.4, p=0.012) was also revealed. Only a trend of negative correlation between serum total protein and anaerobic threshold (r-value -0.3, p=0.07) was found. Interestingly, different responses in MDA levels were elicited by the ergometric test as a function of the individual anaerobic threshold. High aerobic capacities may be promising anthropometric factors indicative of adapted biochemical environments featuring enhanced protection against the oxidative challenge elicited by both regular endurance training and single intense exercise bouts.
Assuntos
Antioxidantes/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Corrida/fisiologia , Adulto , Limiar Anaeróbio/fisiologia , Proteínas Sanguíneas/metabolismo , Ergometria , Teste de Esforço , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Oxirredução , Carbonilação Proteica/fisiologiaRESUMO
In accordance with the classification of the International Agency for Research on Cancer, extremely low frequency magnetic fields (ELF-MF) are suspected to promote malignant progression by providing survival advantage to cancer cells through the activation of critical cytoprotective pathways. Among these, the major antioxidative and detoxification defence systems might be targeted by ELF-MF by conferring cells significant resistance against clinically-relevant cytotoxic agents. We investigated whether the hyperproliferation that is induced in SH-SY5Y human neuroblastoma cells by a 50 Hz, 1 mT ELF magnetic field was supported by improved defence towards reactive oxygen species (ROS) and xenobiotics, as well as by reduced vulnerability against both H2O2 and anti-tumor ROS-generating drug doxorubicin. ELF-MF induced a proliferative and survival advantage by activating key redox-responsive antioxidative and detoxification cytoprotective pathways that are associated with a more aggressive behavior of neuroblastoma cells. This was coupled with the upregulation of the major sirtuins, as well as with increased signaling activity of the erythroid 2-related nuclear transcription factor 2 (NRF2). Interestingly, we also showed that the exposure to 50 Hz MF as low as 100 µT may still be able to alter behavior and responses of cancer cells to clinically-relevant drugs.
Assuntos
Campos Magnéticos , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Oxirredução , Biomarcadores , Linhagem Celular Tumoral , Doxorrubicina/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Inativação Metabólica , Fator 2 Relacionado a NF-E2/metabolismo , Gradação de Tumores , Neuroblastoma/etiologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Sirtuína 3/metabolismoRESUMO
Recent data from literature report that reactive oxygen species (ROS) seem to play a crucial role in the etiology of both types I and II diabetes. This may render diabetic individuals more prone to oxidative injury when challenged with hypoxic stress. It is in fact well known that many diabetic complications cause ischaemic episodes, with a consequent reduction in oxygen supply to various tissues and organs. To check this hypothesis, in this work we tested type I diabetic individuals' antioxidant capability towards a hypoxic-mediated oxidative challenge. In particular, spontaneously diabetic and age-matched non-diabetic biobreeding (BB) Wistar rats were submitted to chronic normobaric hypoxia, and the response of antioxidant enzymes, as well as redox-sensitive transcription factor NF-kappaB and p53, were monitored. Results show that diabetic subjects present a dramatic enhancement in the major antioxidant enzymes activities, thus supporting the notion of diabetes-related changes in cellular redox status. This allows diabetic individuals to counteract hypoxia-mediated oxidative challenge better than the non-diabetic counterpart. Also the behaviour of both the redox-sensitive nuclear transcription factor NF-kappaB and p53 protein in response to hypoxic stimulation seems to support the hypothesis of a better ROS scavenging efficiency in diabetics under hypoxic conditions. In conclusion, high levels of antioxidant enzymatic defences in diabetic BB rats reflect a positive adaptive response able to assure an efficient protection not only against chronic, diabetes-mediated reactive oxygen species (ROS) overproduction, but also versus further oxidative damage.
Assuntos
Antioxidantes/metabolismo , Hipóxia Celular , Diabetes Mellitus/enzimologia , Diabetes Mellitus/patologia , Animais , Caspase 3/metabolismo , Catalase/metabolismo , Diabetes Mellitus/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Lactoilglutationa Liase/metabolismo , Fígado/enzimologia , Pulmão/enzimologia , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Tioléster Hidrolases/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Population aging results in urgent needs of interventions aimed at ensuring healthy senescence. Exercise often results in healthy aging, yet many molecular mechanisms underlying such effects still need to be identified. We here investigated whether the age-dependent accumulation of oxidative and methylglyoxal- (MG-) related molecular damage could be delayed by moderate exercise in the mouse ovary, an organ that first exhibits impaired function with advancing age in mammals. CD1 female mice underwent two- or four-month treadmill-based running through the transition from adult to middle age, when ovaries show signs of senescence, and markers of protection against reactive oxygen species (ROS) and MG were measured. The long-term exercise reduced the protein oxidative damage in the ovaries (P < 0.01), and this was linked to the preservation of the glutathione peroxidase protection against ROS (P < 0.001), as well as to the increased glutathione availability (P < 0.001). Conversely, even though the age-related deactivation of the MG-targeting systems was partially prevented by the long-term running programme (P < 0.001), exercised mice were not protected from the age-dependent glycative burden. In summary, lately initiated regular and moderate exercise limited some changes occurring in the ovaries of middle-aged mice, and this might help to develop nonpharmacological cointerventions to reduce the vulnerability of mammalian ovaries towards redox dysfunctions.
Assuntos
Antioxidantes/metabolismo , Ovário/metabolismo , Envelhecimento , Animais , Catalase/metabolismo , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Lactoilglutationa Liase/genética , Lactoilglutationa Liase/metabolismo , Camundongos , Ornitina/análogos & derivados , Ornitina/metabolismo , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal , Carbonilação Proteica/efeitos dos fármacos , Pirimidinas/metabolismo , Aldeído Pirúvico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismoRESUMO
The effect of the combination of trekking and balanced appropriated diet were studied in mountaineers who spent 6 days at an altitude ranging from 900 to 5895 m above sea level (a.s.l.), during the Kilimanjaro Abruzzo Expedition. This study explored whether anthropometric, cardiovascular and blood biochemical parameters were significantly changed by a regular trekking performed at high altitude, with reduced oxygen levels, together with a macronutrient-containing balanced diet (total daily caloric intake: 3000-3500 Kcals). In consideration of the short period of high-altitude exposure, high-altitude exercise appeared to provide beneficial and rapid effects on the lipid profile and to modulate cardiovascular functions. These effects rely on both high-altitude hypoxia and physical activity. The most interesting observation is that even just a few days of high-altitude exercise, along with a balanced diet, was able to improve plasma lipid profiles.
RESUMO
The role of hydroxyl radicals on the degradation of lignins during a cellulosic pulp bleaching process including a photocatalytic stage, was assessed using peroxyformic acid lignins EL1 and REL1 and two phenolic niphenyl lignin models 1 and 2. The irradiations were performed in the absence of photocatalyst TiO2 and H2O2 (condition a), in the presence of TiO2 (condition b) and in the presence of H2O2 (condition c). The experiments were conducted in alkaline (pH approximately 11) aqueous ethanol solutions with oxygen bubbling. The relative phenolic content of the irradiated solutions, which is indicative of the involvement of hydroxyl radicals, was determined by ionization absorption spectroscopy. The results obtained show that the catalyzed reaction involves both degradation of the phenolate groups by electron transfer and hydroxylation of the lignin aromatic structure. Benzyl alcohol structural elements in sodium borohydride reduced lignin REL1 and compound 2 were also found as good trapping agents for the hydroxyl radicals. The degradation of EL1 was studied by measuring its fluorescence emission by comparison to the fluorescence of compound 2. The emission spectra indicate that some biphenyl phenolate anions in EL1 are reacting under UV/visible irradiation and some others, probably polyphenolic chromophores emitting less fluorescence, are formed.
Assuntos
Celulose/química , Radical Hidroxila , Lignina/química , Fotólise , Titânio , Catálise , Indicadores e Reagentes , CinéticaRESUMO
Despite the demonstrated exercise-induced increase in reactive oxygen species (ROS) production, growing epidemiological evidence indicates that habitual, moderate physical activity reduces the incidence of several oxidative stress-based diseases. This apparent paradox can be explained taking into account that ROS produced during repeated exercise bouts may act as mild stressors able to trigger physiological and biomolecular hormetic responses through a number of redox-sensitive transcription pathways. Unfortunately, much more limited information is available from general population-based research, which could better reflect the condition of common people interested in achieving and maintaining good fitness levels. The present work aimed at investigating whether and how exercise-related habits in non-professional regular runners (n=33) can affect the systemic anti-oxidative capacity, and the resting serum levels of typical lipid peroxidation-related by-products and oxidatively-damaged proteins, in comparison with untrained sedentary individuals (n=25). We also analyzed in both groups the redox response elicited by a modified Bruce-based maximal exercise test on the same parameters. Our findings indicated that long-term regular and moderate practice of aerobic physical activity can increase antioxidant defense systems, lower the resting protein oxidation processes and reduce the immediate up-regulation of lipid-targeting oxidative stress in response to an acute bout of exercise.
Assuntos
Exercício Físico/fisiologia , Adulto , Humanos , Masculino , Músculo Esquelético/fisiologia , Oxirredução , Estresse Oxidativo/fisiologia , Corrida/fisiologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The central role of peroxisomes in ROS and lipid metabolism and their importance in brain functioning are well established. The aim of this work was to study the modulation of peroxisomal and peroxisome-related proteins in cortical neurons in vitro challenged with chronic or acute Abeta treatment, in order to investigate whether peroxisomes represent one of the cellular target of Abeta in these cells. The expression of peroxisomal (PMP70, catalase, acyl-CoA oxidase and thiolase), peroxisome-related (PPARalpha, insulin-degrading enzyme) and anti-oxidant (SOD1, SOD2, GSTP1) proteins was studied. The results obtained, demonstrating an early upregulation of the peroxisomal proteins during the chronic challenge, followed by their dramatic impairment after acute challenge, suggest that peroxisomes represent one of the first line of defence against Abeta-mediated oxidative injury. Our results support the notion that substances able to activate PPARalpha and/or to induce peroxisomal proliferation may constitute a novel preventive and/or therapeutic tool against neurodegenerative diseases.
Assuntos
Peptídeos beta-Amiloides/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Peroxidases/metabolismo , Superóxido Dismutase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Benzotiazóis , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Embrião de Mamíferos , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Indóis , Insulisina/genética , Insulisina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Peroxidases/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/classificação , Superóxido Dismutase/genética , Sais de Tetrazólio , Tiazóis/metabolismo , Fatores de TempoRESUMO
Limited knowledge exists about changes in follicle quality associated with age. The aim of this work was to investigate whether ageing may cause oxidative stress-mediated alterations in human granulosa cells (GCs) from periovulatory follicles. GCs employed in this study were obtained from follicular aspirates of 20 younger women (range 27-32 years) and 20 older women (range 38-41 years) undergoing an IVF treatment. Results obtained from comparative RT-PCR analysis revealed that the mean relative levels of mRNAs coding for superoxide dismutases, Cu, ZnSOD (SOD1), MnSOD (SOD2) and catalase were significantly decreased in women > or =38 years (P < 0.05, Student's t-test). These changes were associated with a reduced expression of SOD1, SOD2 and catalase at the protein level. When examined at an ultrastructural level, most of the GCs from this group showed defective mitochondria and fewer lipid droplets than those observed in the younger group. These results indicate that GCs from older patients suffer from age-dependent oxidative stress injury and are taken as an evidence for reduced defence against reactive oxygen species (ROS) in GCs during reproductive ageing.