Effect of CRH on NO bioavailability, ROS production and antioxidant defense systems in endothelial EAhy926 cells

Local or 'Immune' Corticotropin-Releasing Hormone (CRH) is secreted in peripheral tissues and plays a direct immunomodulatory role as an endocrine or paracrine mediator of inflammation. The present study was undertaken to determine whether CRH affects the endothelial redox state. Accordingly, intracellular reactive oxygen species (ROS) content and peroxynitrite levels, endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) levels as well as catalase activity, superoxide dismutase (SOD) activity and glutathione (GSH) levels were measured in the presence or absence of selective CRH receptor-1 and CRH receptor-2 inhibitors in endothelial EAhy926 cells exposed in vitro in 10(-7) M CRH for 2 h. CRH acting through both receptors induced a significant increase of ROS content (p < 0.001), catalase activity (p < 0.001) and SOD activity (p < 0.001), accompanied by a simultaneous significant decrease of eNOS activity and NO levels (p < 0.001), as well as a significant increase in nitrotyrosine (peroxynitrite) levels (p < 0.05). The data indicate that CRH may act as a regulator of pro-inflammatory mechanisms inducing adaptation of endothelial cell function to local stress

Normal menstrual cycle steroid hormones variation does not affect the blood levels of total adiponectin and its multimer forms

Objective Plasma total adiponectin reveals a sexual dimorphism indicating that gonadal steroids may be involved in its secretion and/or metabolism. However, results from previous reports are conflicting and data regarding the influence of ovarian steroids on adiponectin's multimer forms are scarce. The objective of the study was to assess if total adiponectin and its isoforms are affected by the changes of estradiol and progesterone during the normal menstrual cycle and the association of total adiponectin and its isoforms with the gonadal steroid levels. Materials/methods Quantitative determination of plasma adiponectin and its multimers was conducted in the three phases of an ovulatory cycle in 13 premenopausal women, in the follicular phase of 10 more premenopausal women, in 20 postmenopausal women and in 21 men. Moreover, serum levels of FSH, LH, prolactin, estradiol, progesterone, and testosterone, sex hormone binding globulin, glucose, and insulin were measured. Results The circulating levels of total adiponectin and its multimers were not affected by the normal variation of estradiol and progesterone across the ovulatory menstrual cycle. In the whole number of participants, the total adiponectin and high molecular weight adiponectin levels were significantly different between genders and associated positively with age and sex hormone binding globulin levels, and negatively with testosterone and progesterone levels and the waist/hip ratio. In the multiple logistic regression analysis, after adjustment for age, gender, and sex hormone binding globulin and progesterone levels, significant predictors of total adiponectin levels were the waist/hip ratio and testosterone levels, and of high molecular weight adiponectin the testosterone levels. Conclusions Normal menstrual cycle ovarian steroids are not involved directly in the regulation of secretion and/or metabolism of total adiponectin and its multimers. Testosterone seems to be responsible for the adiponectin's sexual dimorphism. © 2015 Elsevier B.V. All rights reserved

Testosterone and dihydrotestosterone modulate the redox homeostasis of endothelium

The predominance of cardiovascular diseases among men compared to premenopausal women has been attributed to testosterone, which is implicated in vascular remodeling. Molecular mechanisms underlying its role have not been clarified but oxidative stress-induced inflammation may be important. We therefore investigated in vitro the effects of testosterone and dihydrotestosterone, (a nonaromatized androgen), on redox homeostasis in absence (basal conditions) and after corticotropin-releasing hormone-induced pro-oxidant action in macroendothelial cells. More specifically, we explored their role on well-established antioxidant enzymes activity, namely endothelial nitric oxide synthase, superoxide dismutase, catalase, and glutathione. We observed that both androgens significantly increased the intracellular reactive oxygen species levels, endothelial nitric oxide synthase activity, nitric oxide concentration as well as superoxide dismutase activity and decreased catalase activity. These effects of Testosterone and DHT were reversed in the presence of the androgen receptor antagonist, flutamide. Moreover, testosterone and dihydrotestosterone similarly enhanced the stimulatory effect of corticotropin-releasing hormone on intracellular reactive oxygen species levels and superoxide dismutase activity but did not influence the inhibitory effect on endothelial nitric oxide synthase activity, nitric oxide release and catalase activity. Finally, androgens did not have a detectable effect on glutathione levels or the glutathione/glutathione plus glutathione disulfide ratio. Our results reveal that testosterone and DHT rise the intracellular redox threshold of the endothelial cell and increases NO synthesis. These findings suggest that the action of testosterone is affected by the redox status of the endothelium and help to explain its controversial effects on the cardiovascular system. © 2022 International Federation for Cell Biolog

Oxidative Stress and Reduced Antioxidative Status, along with Endothelial Dysfunction in Acromegaly

Acromegaly is characterized by high cardiovascular morbidity and mortality. Oxidative stress and endothelial dysfunction are underlying mechanisms of atherosclerosis. The aim of this study was to evaluate the blood redox status and endothelial function by means of nitric oxide (NO) levels in patients with acromegaly. Total antioxidant capacity (TAC), catalase activity and glutathione concentration (GSH), as measures of antioxidative capacity, total oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS), as indices of oxidative stress, and NO levels were assessed in 15 patients with acromegaly (age 55.4 +/- 10.5 years; 6 males) and 15 age-and sex-matched controls (age 58.4 +/- 8.1 years; 7 males). Active disease was present in 12 patients: 11 on current pharmacotherapy and 1 newly diagnosed. Three acromegalics were in remission after successful treatment. Acromegalics as compared with controls had significantly lower levels of catalase activity (8.2 +/- 5.8 vs. 51.3 +/- 29.1 mmol/ml/min, p < 0.001), GSH (0.97 +/- 0.54 vs. 1.41 +/- 0.35 mmol/l, p = 0.006), GSSG (0.27 +/- 0.19 vs. 2.04 +/- 1.32 mmol/l, p = 0.002) and NO levels (6.0 +/- 3.1 vs. 43.0 +/- 29.8 mmol/l, p < 0.001), but higher TBARS (16.3 +/- 8.9 vs. 10.1 +/- 10.8, nmol/ml, p = 0.019). After adjustment for confounders, differences in catalase activity, NO levels and TBARS remained signifi cant (p = 0.004, p < 0.001 and p = 0.025, respectively). No association between IGF-I/GH and oxidative stress markers was noticed, except for a positive correlation between nadir GH and GSSG (r(2) = 0.563, p = 0.036). Acromegaly is associated with increased levels of oxidative stress coupled by diminished antioxidant capacity and endothelial dysfunction indicated by the presence of decreased NO levels

Serum nitrite and nitrate levels in children with obstructive sleep-disordered breathing

Background: Diminished nitric oxide (NO) levels have been reported in adults with obstructive sleep apnea but no data are available for children with obstructive sleep-disordered breathing (SDB). Objectives: To assess levels of serum NO metabolites in children with SDB and to explore the effects of NO metabolites, SDB and their interaction on blood pressure. Methods: Morning nitrite, the sum of nitrite and nitrate (NO), and the average of evening and morning blood pressure were assessed in children with SDB referred for polysomnography and in controls without SDB. Results: Forty-three children with SDB (age: 5.8 +/- 2.1 years) had moderate-to-severe nocturnal hypoxemia (SpO(2) nadir: 85.6 +/- 4%), 54 subjects (6.6 +/- 2.7 years) had mild hypoxemia (SpO(2) nadir: 91.4 +/- 1.3%) and 20 subjects were controls free of SDB (6.7 +/- 3.7 years). Subjects with moderate-to-severe hypoxemia had significantly lower In-transformed NO metabolites (1.4 +/- 0.7, nitrites; 2.6 +/- 0.5, NO(x)) compared to those with mild hypoxemia (1.9 +/- 0.8, nitrites; 3 +/- 0.6, NO(x)) and controls (2.2 +/- 0.7, nitrite; 3 +/- 0.6, NO(x); p0.05). Conclusions: Moderate-to-severe hypoxemia accompanying SDB is associated with reduced concentrations of morning serum NO metabolites, but NO levels do not seem to affect blood pressure. (C) 2010 Elsevier B.V. All rights reserved

Increased oxidative stress indices in the blood of child swimmers

The blood redox status of child athletes is compared with that of age-matched untrained individuals. In the present study, 17 swimmers (10.1 +/- 1.6 years) and 12 non-athletes (9.9 +/- 1.1 years) participated. Reduced glutathione (GSH) was lower by 37% in swimmers compared to non-athletes (P < 0.01), oxidized glutathione (GSSG) was not different and their ratio (GSH/GSSG) was lower by 43% in swimmers compared to non-athletes (P < 0.01). Thiobarbituric acid-reactive substances concentration was higher by 25% in swimmers compared to controls. Catalase exhibited a strong trend toward lower levels in swimmers (P = 0.08). Finally, total antioxidant capacity was found lower by 28% in swimmers compared to controls (P < 0.05). In conclusion, we report that children participating in swimming training exhibit increased oxidative stress and less antioxidant capacity compared to untrained counterparts and suggest that children may be more susceptible to oxidative stress induced by chronic exercise

Secondhand smoke exposure induces acutely airway acidification and oxidative stress

Previous studies have shown that secondhand smoke induces lung function impairment and increases proinflammatory cytokines. The aim of the present study was to evaluate the acute effects of secondhand smoke on airway acidification and airway oxidative stress in never-smokers. In a randomized controlled cross-over trial, 18 young healthy never-smokers were assessed at baseline and 0, 30, 60, 120, 180 and 240 min after one-hour secondhand smoke exposure at bar/restaurant levels. Exhaled NO and CO measurements, exhaled breath condensate collection (for pH, H2O2 and NO2-/NO3- measurements) and spirometry were performed at all time-points. Secondhand smoke exposure induced increases in serum cotinine and exhaled CO that persisted until 240 min. Exhaled breath condensate pH decreased immediately after exposure (p < 0.001) and returned to baseline by 180 min, whereas H2O2 increased at 120 min and remained increased at 240 min (p = 0.001). No changes in exhaled NO and NO2/NO3 were observed, while decreases in FEV1 (p <0.001) and FEV1/FVC (p < 0.001) were observed after exposure and returned to baseline by 180 min. A 1-h exposure to secondhand smoke induced airway acidification and increased airway oxidative stress, accompanied by significant impairment of lung function. Despite the reversal in EBC pH and lung function, airway oxidative stress remained increased 4 h after the exposure. Clinical trial registration number (EudraCT): 2009-013545-28. (C) 2012 Elsevier Ltd. All rights reserved