Moderate-intensity exercise allows enhanced protection against oxidative stress-induced cardiac dysfunction in spontaneously hypertensive rats.

The progression of myocardial injury secondary to hypertension is a complex process related to a series of physiological and molecular factors including oxidative stress. This study aimed to investigate whether moderate-intensity exercise (MIE) could improve cardiac function and oxidative stress in spontaneously hypertensive rats (SHRs). Eight-week-old male SHRs and age-matched male Wistar-Kyoto rats were randomly assigned to exercise training (treadmill running at a speed of 20 m/min for 1 h continuously) or kept sedentary for 16 weeks. Cardiac function was monitored by polygraph; cardiac mitochondrial structure was observed by scanning electron microscope; tissue free radical production was measured using dihydroethidium staining. Expression levels of SIRT3 and SOD2 protein were measured by western blot, and cardiac antioxidants were assessed by assay kits. MIE improved the cardiac function of SHRs by decreasing left ventricular systolic pressure (LVSP), and first derivation of LVP (+LVdP/dtmax and -LVdP/dtmax). In addition, exercise-induced beneficial effects in SHRs were mediated by decreasing damage to myocardial mitochondrial morphology, decreasing production of reactive oxygen species, increasing glutathione level, decreasing oxidized glutathione level, increasing expression of SIRT3/SOD2, and increasing activity of superoxide dismutase. Exercise training in SHRs improved cardiac function by inhibiting hypertension-induced myocardial mitochondrial damage and attenuating oxidative stresses, offering new insights into prevention and treatment of hypertension.

Increased vascular function and superoxide dismutase activity in physically active vs inactive adults living with HIV.

This study compared macro- and microvascular endothelial function and redox status in active vs inactive HIV-infected patients (HIVP) under antiretroviral therapy. Using a cross-sectional design, macro- and microvascular reactivity, systemic microvascular density, and oxidative stress were compared between 19 HIVP (53.1 ± 6.1 year) enrolled in a multimodal training program (aerobic, strength and flexibility exercises) for at least 12 months (60-minutes sessions performed 3 times/wk with moderate intensity) vs 25 sedentary HIVP (51.2 ± 6.3 year). Forearm blood flow during reactive hyperemia (521.7 ± 241.9 vs 361.4% ± 125.0%; P = 0.04) and systemic microvascular density (120.8 ± 21.1 vs 105.6 ± 25.0 capillaries/mm2 ; P = 0.03) was greater in active than inactive patients. No significant difference between groups was detected for endothelium-dependent and independent skin microvascular vasodilation (P > 0.05). As for redox status, carbonyl groups (P = 0.22), lipid peroxidation (P = 0.86), catalase activity (P = 0.99), and nitric oxide levels (P = 0.72) were similar across groups. However, superoxide dismutase activity was greater in active vs inactive HIVP (0.118 ± 0.013 vs 0.111 ± 0.007 U/mL; P = 0.05). Immune function reflected by total T CD4 and T CD8 counts (cell/mm3 ) did not differ between active and inactive groups (P > 0.82). In conclusion, physically active HIVP exhibited similar immune function, but greater macrovascular reactivity, systemic microvascular density, and superoxide dismutase activity than inactive patients of similar age.

Moderate-intensity exercise allows enhanced protection against oxidative stress-induced cardiac dysfunction in spontaneously hypertensive rats

The progression of myocardial injury secondary to hypertension is a complex process related to a series of physiological and molecular factors including oxidative stress. This study aimed to investigate whether moderate-intensity exercise (MIE) could improve cardiac function and oxidative stress in spontaneously hypertensive rats (SHRs). Eight-week-old male SHRs and age-matched male Wistar-Kyoto rats were randomly assigned to exercise training (treadmill running at a speed of 20 m/min for 1 h continuously) or kept sedentary for 16 weeks. Cardiac function was monitored by polygraph; cardiac mitochondrial structure was observed by scanning electron microscope; tissue free radical production was measured using dihydroethidium staining. Expression levels of SIRT3 and SOD2 protein were measured by western blot, and cardiac antioxidants were assessed by assay kits. MIE improved the cardiac function of SHRs by decreasing left ventricular systolic pressure (LVSP), and first derivation of LVP (+LVdP/dtmax and −LVdP/dtmax). In addition, exercise-induced beneficial effects in SHRs were mediated by decreasing damage to myocardial mitochondrial morphology, decreasing production of reactive oxygen species, increasing glutathione level, decreasing oxidized glutathione level, increasing expression of SIRT3/SOD2, and increasing activity of superoxide dismutase. Exercise training in SHRs improved cardiac function by inhibiting hypertension-induced myocardial mitochondrial damage and attenuating oxidative stresses, offering new insights into prevention and treatment of hypertension.

The effects of an experimentally induced unilateral varicose ovarian vein on the activities of anti-oxidant enzymes in an adult rat ovary / Efectos de la inducción experimental unilateral de una vena ovárica varicosa sobre las actividades de las enzimas anti-oxidantes en ovarios de ratas adultas

In this study, we aim to examine effects of an experimentally induced unilateral varicose ovarian vein on the activities of anti-oxidant enzymes in an adult rat ovary. In this experimental study, a total of 30 adult female Wistar albino rats were divided into three groups. 10 rats in group 1 as the varicocele group, 10 rats in group 2 as the control group and 10 rats in group 3 as the sham group, that underwent a sham operation and. Anti-oxidant assays were assessed via specific assay kits. Statistical analysis was performed using the one way ANOVA and Tukey's tests were used for post hoc multiple comparisons, P<0.05 was considered statistically significant. The effects of the unilateral varicosity was more evident on the left side when compared to the right side as all activities of the anti-oxidant assayed were significantly reduced, P 0.05 when compared to the right side. Also, in this present study, the effect of the unilateral varicose vein was bilateral as there were no significant differences recorded between the two sides. Finally the result of this study shows that varicocele may lead to female infertility through various factors that includes reduction in the activities of anti-oxidant enzymes.

En este estudio, nuestro objetivo fue examinar los efectos de la inducción experimental unilateral de una vena ovárica varicosa en la actividad de enzimas antioxidantes en un ovario de rata adulta. Un total de 30 ratas albinas Wistar, hembras adultas, se dividieron en tres grupos. Diez ratas en el grupo 1 (grupo varicocele), diez ratas en el grupo 2 (grupo de control) y diez ratas en el grupo 3 (grupo de tratamiento simulado), que se sometió a una operación simulada. Ensayos con anti-oxidantes se evaluaron a través de kits de ensayo específicos. El análisis estadístico se realizó mediante ANOVA de una vía y las pruebas de Tukey fueron utilizadas para comparaciones múltiples Post Hoc, siendo el P<0,05 considerado como estadísticamente significativo. Los efectos de la varicosidad unilateral fue más evidente en el lado izquierdo cuando fue comparada con el lado derecho en todas las actividades del ensayo con anti-oxidante que se redujeron significativamente, el P 0,05 cuando se compara con el lado derecho. Asimismo, en el presente estudio, el efecto de la vena varicosa unilateral fue bilateral ya que no hubo diferencias significativas registradas entre las dos partes. Por último, el resultado de este estudio muestra que el varicocele puede conducir a la infertilidad femenina a través de diversos factores que incluye la reducción en la actividad de las enzimas antioxidantes.

A Cu/Zn superoxide dismutase from Jatropha curcas enhances salt tolerance of Arabidopsis thaliana.

Superoxide dismutases (SODs) are involved in protecting plants against diverse biotic and abiotic stresses. In the present study, a novel Cu/Zn-SOD gene (JcCu/Zn-SOD) was cloned from Jatropha curcas L. Quantitative reverse transcription-polymerase chain reaction analysis revealed that JcCu/Zn-SOD is constitutively expressed in different tissues of J. curcas and induced under NaCl treatment. To characterize the function of this gene with respect to salt tolerance, the construct p35S:JcCu/Zn-SOD was developed and transformed into Arabidopsis using Agrobacterium-mediated transformation. Compared with wild-type, transgenic plants over-expressing JcCu/Zn-SOD showed enhanced tolerance to salt stress during germination, seedling establishment, and growth in terms of longer root, larger rosette area, and a larger number of leaves in addition to higher SOD activity levels under NaCl stress. In addition, over-expression of JcCu/Zn-SOD resulted in lower monodialdehyde content in transgenic Arabidopsis compared to wild-type plants under the same NaCl stress. Therefore, JcCu/Zn-SOD can increase a plant salt stress tolerance potentially by reducing oxidant injury.

The age-related changes in SOD activity in bovine (Bos taurus) reproductive organs

Background: The appearance of reactive oxygen species (ROS) is connect with oxidative energy production particularlyin reproductive organs. They characterize by increased metabolism, which may change during ageing. Their increasecould be dangerous for germ cells. That is why the antioxidant protection is need. One of the main antioxidative enzymeis superoxide dismutase (SOD) which could be regulated by steroid hormones through genomic mechanism of action. Buttheir level changed during ageing and maturation. However, there is still lack information about ageing alteration of SODactivity in bovine especially in reproductive organs.Materials, Methods & Results: The material for experiment consisted of reproductive organs: uterus (which was separatedinto endometrium and myometrium), both ovaries and corpus luteum collected immediately after slaughter at the slaughterhouse. Samples were taken from healthy cows aged between 16-24 months (n = 15) during luteal phase of cycle and femalecalves aged between 2 weeks and 2 months (n = 12) Total SOD activity was measured in homogenates of reproductiveorgans by use of the spectrophotometric method. PAGE electrophoresis was performed and Western blotting techniquewith specific anti-SOD antibodies as well as zymography confirmed the presence of enzymatic protein and the activity ofSOD isoenzymes. The results of spectrophotometric determinations showed significant influence of age on SOD activityin examined tissues. The SOD activity not indicate significant differences between examined reproductive organs in thegroup of cows but higher level was noticed in myometrium while the lowest in corpus luteum but the differences betweenovaries in cows were not observed. In the group of female calves as well as in the group of cows the differences betweenSOD activity in reproductive organs were not observed. The higher level was noticed in ovaries but the lower level wasobserved in myometrium...(AU)

The age-related changes in SOD activity in bovine (Bos taurus) reproductive organs

Background: The appearance of reactive oxygen species (ROS) is connect with oxidative energy production particularlyin reproductive organs. They characterize by increased metabolism, which may change during ageing. Their increasecould be dangerous for germ cells. That is why the antioxidant protection is need. One of the main antioxidative enzymeis superoxide dismutase (SOD) which could be regulated by steroid hormones through genomic mechanism of action. Buttheir level changed during ageing and maturation. However, there is still lack information about ageing alteration of SODactivity in bovine especially in reproductive organs.Materials, Methods & Results: The material for experiment consisted of reproductive organs: uterus (which was separatedinto endometrium and myometrium), both ovaries and corpus luteum collected immediately after slaughter at the slaughterhouse. Samples were taken from healthy cows aged between 16-24 months (n = 15) during luteal phase of cycle and femalecalves aged between 2 weeks and 2 months (n = 12) Total SOD activity was measured in homogenates of reproductiveorgans by use of the spectrophotometric method. PAGE electrophoresis was performed and Western blotting techniquewith specific anti-SOD antibodies as well as zymography confirmed the presence of enzymatic protein and the activity ofSOD isoenzymes. The results of spectrophotometric determinations showed significant influence of age on SOD activityin examined tissues. The SOD activity not indicate significant differences between examined reproductive organs in thegroup of cows but higher level was noticed in myometrium while the lowest in corpus luteum but the differences betweenovaries in cows were not observed. In the group of female calves as well as in the group of cows the differences betweenSOD activity in reproductive organs were not observed. The higher level was noticed in ovaries but the lower level wasobserved in myometrium...

Sistema antioxidante enzimático e indicadores de daño oxidativo en pacientes diabéticos tipo 2 / Antioxidant enzymatic system and oxidative damage indicators in patients with type 2 diabetes

Several biological processes are involved in the oxidative stress present in diabetes mellitus; among them we can find glucose autooxidation, proteins glycation and decreased antioxidant defenses. Free radicals yielded at mitochondrial level could be a trigger to unchain the vicious circle of the oxidative stress in diabetes mellitus. Aims: to determine antioxidant system’s alterations and indicators of oxidative damage on lipids and proteins in patients with type II Diabetes and a control group. Materials and Methods: It was analyzed 120 serum samples; 60 from patients that suffer type II diabetic from endocrinology surgery belonging “Casa de atención al paciente diabético”in Santa Clara, Villa Clara and 60 samples from healthy individuals used as control group. Spectrofotometric techniques were used to assess levels of Superoxide dismutase and Catalase activity as well as concentrations of reduced glutathione, malonildialdehide and advanced products of proteins Oxidation. Results were compared using the statistical software SPSS. Results: Diabetes type 2 patients showed decreased of Superoxide Dismutase and Catalase enzymatic activity (p = 0,003) and (p = 0,013) respectively as well as and reduced Glutathione levels (p = 0,038). Malondialdehide and Advanced Products of Proteins Oxidation were increased (p = 0,000) in diabetics patients compared with control group. Conclusions: it was found redox alterations in patients that suffer type 2 Diabetes. These alterations are evidenced by a reduced antioxidant enzymatic system and damage on macromolecules such as lipids and proteins...

Tempol moderately extends survival in a hSOD1(G93A) ALS rat model by inhibiting neuronal cell loss, oxidative damage and levels of non-native hSOD1(G93A) forms.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive dysfunction and death of motor neurons by mechanisms that remain unclear. Evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. Cyclic nitroxides are an alternative worth exploring because they are multifunctional antioxidants that display low toxicity in vivo. Here, we examine the effects of the cyclic nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) on ALS onset and progression in transgenic female rats over-expressing the mutant hSOD1(G93A) . Starting at 7 weeks of age, a high dose of tempol (155 mg/day/rat) in the rat´s drinking water had marginal effects on the disease onset but decelerated disease progression and extended survival by 9 days. In addition, tempol protected spinal cord tissues as monitored by the number of neuronal cells, and the reducing capability and levels of carbonylated proteins and non-native hSOD1 forms in spinal cord homogenates. Intraperitoneal tempol (26 mg/rat, 3 times/week) extended survival by 17 days. This group of rats, however, diverted to a decelerated disease progression. Therefore, it was inconclusive whether the higher protective effect of the lower i.p. dose was due to higher tempol bioavailability, decelerated disease development or both. Collectively, the results show that tempol moderately extends the survival of ALS rats while protecting their cellular and molecular structures against damage. Thus, the results provide proof that cyclic nitroxides are alternatives worth to be further tested in animal models of ALS.

Superoxide dismutases and glutaredoxins have a distinct role in the response of Candida albicans to oxidative stress generated by the chemical compounds menadione and diamide

To cope with oxidative stress, Candida albicans possesses several enzymes involved in a number of biological processes, including superoxide dismutases (Sods) and glutaredoxins (Grxs). The resistance of C. albicans to reactive oxygen species is thought to act as a virulence factor. Genes such as SOD1 and GRX2, which encode for a Sod and Grx, respectively, in C. albicans are widely recognised to be important for pathogenesis. We generated a double mutant, Δgrx2/sod1, for both genes. This strain is very defective in hyphae formation and is susceptible to killing by neutrophils. When exposed to two compounds that generate reactive oxygen species, the double null mutant was susceptible to menadione and resistant to diamide. The reintegration of the SOD1 gene in the null mutant led to recovery in resistance to menadione, whereas reintegration of the GRX2 gene made the null mutant sensitive to diamide. Despite having two different roles in the responses to oxidative stress generated by chemical compounds, GRX2 and SOD1 are important for C. albicans pathogenesis because the double mutant Δgrx2/sod1 was very susceptible to neutrophil killing and was defective in hyphae formation in addition to having a lower virulence in an animal model of systemic infection.

Mitochondrial functions in astrocytes: neuroprotective implications from oxidative damage by rotenone.

Mitochondria are critical for cell survival and normal development, as they provide energy to the cell, buffer intracellular calcium, and regulate apoptosis. They are also major targets of oxidative stress, which causes bioenergetics failure in astrocytes through the activation of different mechanisms and production of oxidative molecules. This review provides an insightful overview of the recent discoveries and strategies for mitochondrial protection in astrocytes. We also discuss the importance of rotenone as an experimental approach for assessing oxidative stress in the brain and delineate some molecular strategies that enhance mitochondrial function in astrocytes as a promising strategy against brain damage.

Influence of Val16Ala SOD2 polymorphism on the in-vitro effect of clomiphene citrate in oxidative metabolism.

This study investigated the in-vitro antioxidant properties of the ovulation induction drug, clomiphene citrate, and assessed whether its effects are influenced by the Val16Ala polymorphism in the SOD2 gene, which encodes manganese superoxide dismutase enzyme. The investigation involved an in-vitro experimental protocol testing the effect of different concentrations of clomiphene citrate on antioxidant capacity, reactive oxygen species (ROS) production and peripheral blood mononuclear cell (PBMC) culture viability. A total of 58 healthy adult women were genotyped for the Val16Ala SOD2 polymorphism, and blood samples were collected to perform in-vitro experiments. ROS production and cytotoxicity assays were performed on blood and PBMC from carriers of different Val16Ala SOD2 genotypes. Clomiphene citrate exhibited antioxidant capacity and effects and decreased ROS production. The AA genotype displayed a more responsive antioxidant effect with clomiphene citrate treatment than other genotypes. AA and AV PBMC showed an increase in viability following treatment with 10 µmol/l clomiphene citrate when compared with control groups. The results suggest that clomiphene citrate exhibits antioxidant activity similar to that observed with other selective oestrogen receptor modulators, and the intensity of the effect appears to be SOD2 polymorphism dependent. This study was performed to investigate whether clomiphene citrate, a drug broadly used to evaluate reproductive function in women, presents antioxidant effects and if these effects could be influenced by genetic variation in the women. We found evidence that clomiphene citrate has some antioxidant properties similar to those observed with other selective oestrogen receptor modulators such as tamoxifen. As the antioxidant enzyme manganese superoxide dismutase (SOD2) is considered a key molecule involved in female reproductive metabolism, we also tested if a functional SOD2 gene polymorphism (Val16Ala) could influence the in-vitro antioxidant clomiphene citrate response. Significant differences of the clomiphene citrate antioxidant effect on PBMC with different Val16Ala SOD genotypes were observed in this study. Based on these results, we could speculate that alterations in SOD2 activity caused by the Val16Ala polymorphism can result in differential responses to drugs such as clomiphene citrate. In assisted reproduction clinics, clomiphene citrate is commonly used to induce ovulation, especially in patients with polycystic ovary syndrome. However, some women have clomiphene citrate resistance and either ovulation is not triggered by the drug or ovulation is induced but the pregnancy still fails. The causes of no effect of clomiphene citrate remain unclear and we cannot discard the influence of genetic effects including the Val16Ala SOD2 polymorphism. Therefore, it is important to perform complementary investigations considering the potential pharmacogenetic influence of Val16Ala SOD2 polymorphism on the treatment of polycystic ovary syndrome or in ovulation to elucidate this question.

Superoxide dismutases and glutaredoxins have a distinct role in the response of Candida albicans to oxidative stress generated by the chemical compounds menadione and diamide.

To cope with oxidative stress, Candida albicans possesses several enzymes involved in a number of biological processes, including superoxide dismutases (Sods) and glutaredoxins (Grxs). The resistance of C. albicans to reactive oxygen species is thought to act as a virulence factor. Genes such as SOD1 and GRX2, which encode for a Sod and Grx, respectively, in C. albicans are widely recognised to be important for pathogenesis. We generated a double mutant, Δgrx2/sod1, for both genes. This strain is very defective in hyphae formation and is susceptible to killing by neutrophils. When exposed to two compounds that generate reactive oxygen species, the double null mutant was susceptible to menadione and resistant to diamide. The reintegration of the SOD1 gene in the null mutant led to recovery in resistance to menadione, whereas reintegration of the GRX2 gene made the null mutant sensitive to diamide. Despite having two different roles in the responses to oxidative stress generated by chemical compounds, GRX2 and SOD1 are important for C. albicans pathogenesis because the double mutant Δgrx2/sod1 was very susceptible to neutrophil killing and was defective in hyphae formation in addition to having a lower virulence in an animal model of systemic infection.

Efeito do exercício físico e do polimorfismo T-786C na pressão arterial e no fluxo sanguíneo de idosas / Effect of physical activity and t-786C polymorphism in blood pressure and blood flow in the elderly / Efecto del ejercicio físico y del polimorfismo T-786C en la presión arterial y en el flujo sanguíneo de añosas

FUNDAMENTO: O polimorfismo T-786C do gene da sintetase do óxido nítrico endotelial (eNOS) e a produção de ânion superóxido podem diminuir a produção e biodisponibilidade do óxido nítrico, comprometendo o grau de vasodilatação, podendo este efeito ser revertido pelo exercício físico. OBJETIVO: Investigar a influência do treinamento aeróbico e do polimorfismo T-786C nas concentrações dos metabólitos do óxido nítrico (NOx), no fluxo sanguíneo (FS) e na pressão arterial (PA). MÉTODOS: Trinta e duas idosas pré-hipertensas (59 ± 6 anos) foram separadas em dois grupos de acordo com o polimorfismo T-786C (TT e TC+CC). Foram analisadas as concentrações de NOx (plasma) e fluxo sanguíneo por pletismografia de oclusão venosa em repouso, 1, 2 e 3 minutos pós-oclusão (FS-0, FS-1, FS-2, FS-3, respectivamente). As avaliações foram realizadas antes e após 6 meses de um programa de exercício aeróbico. RESULTADOS: Nas avaliações pré-treinamento, os níveis de NOx foram menores no grupo TC+CC em relação ao grupo TT. O grupo TT apresentou correlações entre NOx e FS-0 (r = 0,6) e pressão arterial diastólica (PAD) e FS-0 (r = -0,7), porém nenhuma correlação foi encontrada no grupo TC+CC. Nas avaliações pós-treinamento, ocorreram correlações entre NOx e FS-0 (r = 0,6) e nas mudanças do NOx e PAD (r = -0,6) no grupo TT. Também foram obtidas correlações entre PAD e FS-1 (r = -0,8), PAD e FS-2 (r = -0,6), PAD e FS-3 (r = -0,6), nas mudanças entre NOx e FS-1 (r = 0,8) e mudanças do NOx e PAD (r = -0,7) no grupo TC+CC. CONCLUSÃO: Conclui-se que 6 meses de exercício aeróbico podem contribuir para aumentar as relações existentes entre NO, PA e FS em idosas portadores do alelo C.

BACKGROUND: The T-786C polymorphism of the gene for endothelial nitric oxide synthase (eNOS) and superoxide anion production may reduce production and bioavailability of nitric oxide, affecting the degree of vasodilation. This effect can be reversed by exercise. OBJECTIVE: To investigate the influence of aerobic training and T-786C polymorphism in the concentrations of nitric oxide metabolites (NOx) in blood flow (BF) and blood pressure (BP). METHODS: Thirty-two elderly pre-hypertensive women (59 ± 6 years old) were divided into two groups according to the T-786C polymorphism (TT and TC + CC). We analyzed the concentrations of NOx (plasma) and blood flow by venous occlusion plethysmography at rest, 1, 2 and 3 minutes post-occlusion (BF-0, BF-1 BF-2 BF-3, respectively). Evaluations were performed before and after 6 months of a program of aerobic exercise. RESULTS: In the pre-training evaluations, NOx levels were lower in TC + CC group than in TT group. The TT group showed correlations between NOx and BF-0 (r = 0.6) and diastolic blood pressure (DBP) and BF-0 (r = -0.7), but no correlation was found in TC + CC group. In the post-training evaluations, there were correlations between NOx and BF-0 (r = 0.6) and the changes in NOx and DBP (r = -0.6) in TT group. There were also correlations between DBP and BF-1 (r = -0.8), DBP, and BF-2 (r = -0.6), DBP, and BF-3 (r = -0.6), in the changes between NOx and BF-1 (r = 0.8) and changes in NOx and DBP (r = -0.7) in TC + CC group. CONCLUSION: It was concluded that 6 months of aerobic exercise can increase the relationship between NO, BP and BF in elderly of allele C carriers.

FUNDAMENTO: El polimorfismo T-786C del gen de la sintetasa del óxido nítrico endotelial (eNOS) y la producción de anión superóxido pueden disminuir la producción y biodisponibilidad del óxido nítrico, comprometiendo el grado de vasodilatación, pudiendo este efecto ser revertido por el ejercicio físico. OBJETIVO: Investigar la influencia del entrenamiento aeróbico y del polimorfismo T-786C en las concentraciones de los metabolitos del óxido nítrico (NOx), en el flujo sanguíneo (FS) y en la presión arterial (PA). MÉTODOS: Treinta y dos añosas prehipertensas (59 ± 6 años) fueron separadas en dos grupos de acuerdo con el polimorfismo T-786C (TT y TC+CC). Fueron analizadas las concentraciones de NOx (plasma) y flujo sanguíneo por pletismografía de oclusión venosa en reposo, 1, 2 y 3 minutos post oclusión (FS-0, FS-1, FS-2, FS-3, respectivamente). Las evaluaciones fueron realizadas antes y después de 6 meses de un programa de ejercicio aeróbico. RESULTADOS: En las evaluaciones pre entrenamiento, los niveles de NOx fueron menores en el grupo TC+CC en relación al grupo TT. El grupo TT presentó correlaciones entre NOx y FS-0 (r = 0,6) y presión arterial diastólica (PAD) y FS-0 (r = -0,7), sin embargo ninguna correlación fue encontrada en el grupo TC+CC. En las evaluaciones post entrenamiento, ocurrieron correlaciones entre NOx y FS-0 (r = 0,6) y en los cambios del NOx y PAD (r = -0,6) en el grupo TT. También fueron obtenidas correlaciones entre PAD y FS-1 (r = -0,8), PAD y FS-2 (r = -0,6), PAD y FS-3 (r = -0,6), en los cambios entre NOx y FS-1 (r = 0,8) y cambios del NOx y PAD (r = -0,7) en el grupo TC+CC. CONCLUSIÓN: Se concluye que 6 meses de ejercicio aeróbico pueden contribuir a aumentar las relaciones existentes entre NO, PA y FS en añosas portadoras del alelo C.

[Effect of physical activity and t-786C polymorphism in blood pressure and blood flow in the elderly]. / Efeito do exercício físico e do polimorfismo T-786C na pressão arterial e no fluxo sanguíneo de idosas.

BACKGROUND: the T-786C polymorphism of the gene for endothelial nitric oxide synthase (eNOS) and superoxide anion production may reduce production and bioavailability of nitric oxide, affecting the degree of vasodilation. This effect can be reversed by exercise. OBJECTIVE: to investigate the influence of aerobic training and T-786C polymorphism in the concentrations of nitric oxide metabolites (NOx) in blood flow (BF) and blood pressure (BP). METHODS: thirty-two elderly pre-hypertensive women (59 ± 6 years old) were divided into two groups according to the T-786C polymorphism (TT and TC + CC). We analyzed the concentrations of NOx (plasma) and blood flow by venous occlusion plethysmography at rest, 1, 2 and 3 minutes post-occlusion (BF-0, BF-1 BF-2 BF-3, respectively). Evaluations were performed before and after 6 months of a program of aerobic exercise. RESULTS: In the pre-training evaluations, NOx levels were lower in TC + CC group than in TT group. The TT group showed correlations between NOx and BF-0 (r = 0.6) and diastolic blood pressure (DBP) and BF-0 (r = -0.7), but no correlation was found in TC + CC group. In the post-training evaluations, there were correlations between NOx and BF-0 (r = 0.6) and the changes in NOx and DBP (r = -0.6) in TT group. There were also correlations between DBP and BF-1 (r = -0.8), DBP, and BF-2 (r = -0.6), DBP, and BF-3 (r = -0.6), in the changes between NOx and BF-1 (r = 0.8) and changes in NOx and DBP (r = -0.7) in TC + CC group. CONCLUSION: it was concluded that 6 months of aerobic exercise can increase the relationship between NO, BP and BF in elderly of allele C carriers.

Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants.

Mitochondrial dysfunction and oxidative stress contribute to motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Recent reports indicate that astrocytes expressing the mutations of superoxide dismutase-1 (SOD1) may contribute to motor neuron injury in ALS. Here, we provide evidence that mitochondrial dysfunction in SOD1(G93A) rat astrocytes causes astrocytes to induce apoptosis of motor neurons. Mitochondria from SOD1(G93A) rat astrocytes displayed a defective respiratory function, including decreased oxygen consumption, lack of ADP-dependent respiratory control, and decreased membrane potential. Protein 3-nitrotyrosine was detected immunochemically in mitochondrial proteins from SOD1(G93A) astrocytes, suggesting that mitochondrial defects were associated with nitroxidative damage. Furthermore, superoxide radical formation in mitochondria was increased in SOD1(G93A) astrocytes. Similar defects were found in mitochondria isolated from the spinal cord of SOD1(G93A) rats, and pretreatment of animals with the spin trap 5,5-dimethyl-1-pyrroline N-oxide restored mitochondrial function, forming adducts with mitochondrial proteins in vivo. As shown previously, SOD1(G93A) astrocytes induced death of motor neurons in cocultures, compared with nontransgenic ones. This behavior was recapitulated when nontransgenic astrocytes were treated with mitochondrial inhibitors. Remarkably, motor neuron loss was prevented by preincubation of SOD1(G93A) astrocytes with antioxidants and nitric oxide synthase inhibitors. In particular, low concentrations (approximately 10 nm) of two mitochondrial-targeted antioxidants, ubiquinone and carboxy-proxyl nitroxide, each covalently coupled to a triphenylphosphonium cation (Mito-Q and Mito-CP, respectively), prevented mitochondrial dysfunction, reduced superoxide production in SOD1(G93A) astrocytes, and restored motor neuron survival. Together, our results indicate that mitochondrial dysfunction in astrocytes critically influences motor neuron survival and support the potential pharmacological utility of mitochondrial-targeted antioxidants in ALS treatment.

Oxidative stress response in eukaryotes: effect of glutathione, superoxide dismutase and catalase on adaptation to peroxide and menadione stresses in Saccharomyces cerevisiae.

Aiming to clarify the mechanisms by which eukaryotes acquire tolerance to oxidative stress, adaptive and cross-protection responses to oxidants were investigated in Saccharomyces cerevisiae. Cells treated with sub-lethal concentrations of menadione (a source of superoxide anions) exhibited cross-protection against lethal doses of peroxide; however, cells treated with H2O2 did not acquire tolerance to a menadione stress, indicating that menadione response encompasses H2O2 adaptation. Although, deficiency in cytoplasmic superoxide dismutase (Sod1) had not interfered with response to superoxide, cells deficient in glutathione (GSH) synthesis were not able to acquire tolerance to H2O2 when pretreated with menadione. These results suggest that GSH is an inducible part of the superoxide adaptive stress response, which correlates with a decrease in the levels of intracellular oxidation. On the other hand, neither the deficiency of Sod1 nor in GSH impaired the process of acquisition of tolerance to H2O2 achieved by a mild pretreatment with peroxide. Using a strain deficient in the cytosolic catalase, we were able to conclude that the reduction in lipid peroxidation levels produced by the adaptive treatment with H2O2 was dependent on this enzyme. Corroborating these results, the pretreatment with low concentrations of H2O2 promoted an increase in catalase activity.

A systems biology analysis of protein-protein interactions between yeast superoxide dismutases and DNA repair pathways.

Superoxide dismutases (SODs) are widely distributed in eukaryotic and prokaryotic species and are responsible for O(2)(.-) scavenging and dismutation to H(2)O(2) and O(2). Mutations in the cytoplasmic (Sod1p) or mitochondrial (Sod2p) form of SODs result in aging, neurodegenerative diseases, and carcinogenesis. Diminished activity of SODs leads to reduced activity of DNA repair pathways, and overexpression of SODs in cells defective for DNA repair increases their level of chromatin damage. Unfortunately, little is understood regarding the interplay between SODs and DNA repair proteins and their role in protecting the genome from oxidative damage. To elucidate the association between yeast SODs and DNA repair mechanisms, a systems biology study was performed employing algorithms of literature data mining and the construction of physical protein-protein interactions from large yeast protein databases. The results obtained in this work allow us to draw two models suggesting that yeast SODs act as O(2)(.-) sensors under conditions of redox imbalance, activating and controlling specific DNA repair mechanisms (e.g., recombinational and excision repair pathways), chromatin remodeling, and synthesis of dNTPs.

Association of mitochondrial SOD deficiency with salt-sensitive hypertension and accelerated renal senescence.

Mitochondria are the major source of superoxide (O(2)(-)) in the aerobic organisms. O(2)(-) produced by the mitochondria is converted to hydrogen peroxide by mitochondrial superoxide dismutase (SOD2). Mice with complete SOD2 deficiency (SOD2(-/-)) exhibit dilated cardiomyopathy and fatty liver leading to neonatal mortality, whereas mice with partial SOD2 deficiency (SOD2(+/-)) show evidence of O(2)(-)-induced mitochondrial damage resembling cell senescence. Since earlier studies have provided compelling evidence for the role of oxidative stress and tubulointerstitial inflammation in the pathogenesis of hypertension, we tested the hypothesis that partial SOD2 deficiency may result in hypertension. Wild-type (SOD2(+/+)) and partial SOD2-deficient (SOD2(+/-)) mice had similar blood pressures at 6-7 mo of age, but at 2 yr SOD2(+/-) mice had higher blood pressure. Oxidative stress, renal interstitial T-cell and macrophage infiltration, tubular damage, and glomerular sclerosis were all significantly increased in 2-yr-old SOD2(+/-) mice. High-salt diet induced hypertension in 6-mo-old SOD2-deficient mice but not in wild-type mice. In conclusion, partial SOD2 deficiency results in oxidative stress and renal interstitial inflammation, changes compatible with accelerated renal senescence and salt-sensitive hypertension. These findings are consistent with the pattern described in numerous other models of salt-sensitive hypertension and resemble that commonly seen in elderly humans.