DHEA Treatment Effects on Redox Environment in Skeletal Muscle of Young and Aged Healthy Rats.

BACKGROUND: Dehydroepiandrosterone (DHEA) is an important precursor of active steroid hormone, produced abundantly by the adrenal cortex with an age-dependent pattern. OBJECTIVE: We investigated whether chronic DHEA administration impacts on redox status and on Akt protein activation in skeletal muscle during the aging process (3 and 24 months-old rats). METHODS: Rats received one weekly dose/5 weeks of DHEA (10 mg/kg) or vehicle. Gastrocnemius muscle was removed to evaluate glutathione system, hydrogen peroxide, antioxidant enzymes, and expression of Akt kinase protein. RESULTS: In the 3-months-old rats DHEA induced an increase in hydrogen peroxide when compared both to its control (276%) and the 24-months-old DHEA group (485%). Moreover, in the 24- months-old rats DHEA caused an increase in GSSG (41 and 28%), a decrease in reduced-GSH (55 and 51%), and a more oxidized redox status (reduction in GSH/GSSG ratio, 47 and 65 %) when compared to 3-month-old DHEA and to 24-months-old control groups, respectively. Both older groups had increased G6PDH (2.7 fold) and GST (1.7 fold) activities when compared to younger groups, independently of any DHEA treatment. However, there was no modulation of Akt protein (phosphorylated/total isoform). CONCLUSION: The results show that chronic DHEA administration to 3 and 24-months-old rats may not present positive effects regarding the redox environment in skeletal muscle without modulation of pro-survival Akt kinase. Due to the large-scale self-administration of DHEA as an "anti-aging" dietary supplement, it is crucial to investigate its molecular mechanisms over oxidative stressinduced related diseases.

Effects of thyroid hormones on aortic tissue after myocardial infarction in rats.

Studies have shown a cardioprotective role of thyroid hormones (THs) in cardiac remodeling after acute myocardial infarction (MI). However, there is no data in the literature examining the influence of TH administration on the aortic tissue in an animal model of MI. This study aimed to evaluate the effects of thyroid hormones on the aorta after MI. Male Wistar rats were divided into a sham group (SHAM), infarcted group (AMI), sham+TH (SHAMT) and AMI+TH (AMIT). After MI, the animals received T3 and T4 (2 and 8µg/100g/day, respectively) by oral gavage for 12 days. Later, the animals underwent echocardiography and euthanasia and the aorta was collected for molecular and biochemical analysis. T3 and T4 administration increased the expression of the pro-angiogenic proteins vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF-1α) in the aorta of AMIT rats when compared with AMI. With respect to TH receptors, AMI rats presented a decrease in TRß levels, which was prevented by the hormonal administration. In AMIT rats, both TRα and TRß levels were increased when compared with the AMI group. Reactive oxygen species levels and NADPH oxidase activity were decreased in both treated groups when compared with the non-treated animals. TH administration after MI may improve angiogenic signaling in the aorta as well as the responsiveness of this vessel to T3 and T4. These positive effects in the aorta may result in additional protection for the cardiovascular system in the context of cardiac ischaemic injury.

Thyroid hormones effects on oxidative stress and cardiac remodeling in the right ventricle of infarcted rats.

UNLABELLED: Right ventricle (RV) dysfunction post-myocardial infarction (MI) was associated with a worsened prognosis. In this scenario, reactive oxygen species (ROS) are related with the progression from MI to heart failure. Previous work showed that thyroid hormones (TH) are cardioprotective after MI. AIMS: This study aims to investigate the effect of T3 and T4 administration on oxidative stress and angiogenesis parameters in the RV after MI. MAIN METHODS: Wistar rats were allocated into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT), and infarcted+TH (AMIT). The treated groups received T3 (2 µg/100g/day) and T4 (8 µg/100g/day) by gavage for 26 days. After this, echocardiographic analysis was performed and the RV was collected to western blot and biochemical analysis. KEY FINDINGS: Infarcted treated rats showed RV hypertrophy compared with AMI and SHAMT. Hydrogen peroxide levels were decrease and SOD activity and expression were increased in the infarcted treated rats. Besides that, the hormonal administration increased eNOS expression and prevented the reduction of VEGF levels in AMIT rats. SIGNIFICANCE: In conclusion, TH seems to improve oxidative stress parameters, to promote physiological hypertrophy and to increase the expression of proteins involved with angiogenesis in the right heart.

Modulation of apoptosis by sulforaphane is associated with PGC-1α stimulation and decreased oxidative stress in cardiac myoblasts.

Sulforaphane is a naturally occurring isothiocyanate capable of stimulating cellular antioxidant defenses and inducing phase 2 detoxifying enzymes, which can protect cells against oxidative damage. Oxidative stress and apoptosis are intimately involved in the pathophysiology of cardiac diseases. Although sulforaphane is known for its anticancer benefits, its role in cardiac cells is just emerging. The aim of the present study was to investigate whether sulforaphane can modulate oxidative stress, apoptosis, and correlate with PGC-1α, a transcriptional cofactor involved in energy metabolism. H9c2 cardiac myoblasts were incubated with R-sulforaphane 5 µmol/L for 24 h. Cell viability, ANP gene expression, oxidative stress and apoptosis markers, and protein expression of PGC-1α were studied. In cells treated with sulforaphane, cellular viability increased (12 %) and ANP gene expression decreased (46 %) compared to control cells. Moreover, sulforaphane induced a significant increase in superoxide dismutase (103 %), catalase (101 %), and glutathione S-transferase (72 %) activity, reduced reactive oxygen species levels (15 %) and lipid peroxidation (65 %), as well as stimulated the expression of the cytoprotective enzyme heme oxygenase-1 (4-fold). Sulforaphane also promoted an increase in the expression of the anti-apoptotic protein Bcl-2 (60 %), decreasing the Bax/Bcl-2 ratio. Active Caspase 3\7 and p-JNK/JNK were also reduced by sulforaphane, suggesting a reduction in apoptotic signaling. This was associated with an increased protein expression of PGC-1α (42 %). These results suggest that sulforaphane offers cytoprotection to cardiac cells by activating PGC1-α, reducing oxidative stress, and decreasing apoptosis signaling.

Catalase influence in the regulation of coronary resistance by estrogen: joint action of nitric oxide and hydrogen peroxide.

We tested the influence of estrogen on coronary resistance regulation by modulating nitric oxide (NO) and hydrogen peroxide (H2O2) levels in female rats. For this, estrogen levels were manipulated and the hearts were immediately excised and perfused at a constant flow using a Langendorff's apparatus. Higher estrogen levels were associated with a lower coronary resistance, increased nitric oxide bioavailability, and higher levels of H2O2. When oxide nitric synthase blockade by L-NAME was performed, no significant changes were found in coronary resistance of ovariectomized rats. Additionally, we found an inverse association between NO levels and catalase activity. Taken together, our data suggest that, in the absence of estrogen influence and, therefore, reduced NO bioavailability, coronary resistance regulation seems to be more dependent on the H2O2 that is maintained at low levels by increased catalase activity.

Low-dose estrogen is as effective as high-dose treatment in rats with postmenopausal hypertension.

: This study was conducted to test the hypothesis that 17ß-estradiol therapy improves redox balance by decreasing reactive oxygen species production and increasing nitric oxide (NO) bioavailability, favoring Akt pathway activation and resulting in a better autonomic vascular control. Ovariectomized female Wistar rats were divided into 4 groups: (1) vehicle (VL) and animals treated with a pellet of 17ß-estradiol for 21 days; (2) low dose (LE; 0.05 mg); (3) medium dose (ME; 0.2 mg); and (4) high dose (HE; 0.5 mg). Arterial pressure and its sympathetic nervous system modulation were evaluated by spectral analysis. Nitric oxide synthase and NADPH oxidase (Nox) activities, H2O2 concentration, redox status (GSH/GSSG), protein expression of Trx-1 and p-Akt/Akt were evaluated in the aorta, whereas NO metabolites were measured in the serum. Estrogen-treated groups showed a significant decrease in arterial pressure and sympathetic vascular drive. Redox status was significantly improved and NADPH oxidase and H2O2 were decreased in all estrogen-treated groups. Estrogen also induced an enhancement in NO metabolites, nitric oxide synthase activity, and Akt phosphorylation. This study demonstrated that estrogen treatment to ovariectomized rats induced cardioprotection, which was evidenced by reduced blood pressure variability and vascular sympathetic drive. These effects were associated with an improved redox balance and Akt activation, resulting in an enhanced NO bioavailability.