Redox status assessment in infertile patients with non‐obstructive azoospermia undergoing testicular sperm extraction: A prospective study

AbstractBackgroundOxidative stress (OS) is one of the most prevalent causes of sperm damage, through the toxic effects of endogenously generated hydrogen peroxide, superoxide anion, and hydroxyl radicals. Peripheral leukocytes represent a feasible model for studying the pathophysiology of OS‐mediated homeostasis, which can be responsible for cell dysfunction and cell injury.ObjectiveTo evaluate the redox status in patients with non‐obstructive azoospermia (NOA), establishing the potential role exerted by reactive oxygen species (ROS) in the genesis of testicular secretory injury.Material and methodsFrom May 2018 to March 2019, 39 patients were enrolled in this prospective single‐center cohort study and divided into two groups. Group 1 included 19 patients with NOA, and Group 2 included 20 normozoospermic men, partners of women with infertility tubal factor. All patients underwent serum blood tests. NOA underwent testicular sperm extraction (TeSE). ROS production (in lymphocytes, monocytes, and granulocytes) was assessed by fluorescence‐activated cell sorting (FACS) analysis. Plasma oxidative stress was evaluated by lipid peroxidation markers (MDA) and total antioxidant capacity (TAC) both assessed by fluorometric techniques.ResultsMean lymphocyte ROS production resulted 967.0 ± 224.5 vs 728.0 ± 98.0 (NOA vs Controls, P .05).ConclusionROS production can be directly related to disorders of spermatogenesis, leading to severe conditions of male infertility, including azoospermia

SIRT1 and thrombosis

Thrombosis is a major cause of morbidity and mortality worldwide, with a complex and multifactorial pathogenesis. Recent studies have shown that SIRT1, a member of the sirtuin family of NAD + -dependent deacetylases, plays a crucial role in regulating thrombosis, modulating key pathways including endothelial activation, platelet aggregation, and coagulation. Furthermore, SIRT1 displays anti-inflammatory activity both in vitro, in vivo and in clinical studies, particularly via the reduction of oxidative stress. On these bases, several studies have investigated the therapeutic potential of targeting SIRT1 for the prevention of thrombosis. This review provides a comprehensive and critical overview of the main preclinical and clinical studies and of the current understanding of the role of SIRT1 in thrombosis

Atherosclerosis and Endometriosis: The Role of Diet and Oxidative Stress in a Gender-Specific Disorder

Background: Accelerated atherosclerosis in patients with endometriosis has been hypothesised, and lifestyle improvement might control cardiovascular risk. We explored cardiometabolic markers and oxidative stress and evaluated the effects of the Mediterranean Diet (MD) in modulating these markers. Methods: In this prospective study, we included 35 women with endometriosis. At baseline (T0) and after 3 (T1) and 6 (T2) months from the start of the diet, we investigated cardiometabolic parameters, lifestyle and oxidative stress. Results: After a 3-month intervention with MD, we observed a significant reduction in total cholesterol (p = 0.01) and LDL-c (p = 0.003). We observed at T1 an increase in B12 and E vitamins, folate and zinc. After 6 months, zinc (p = 0.04) and folate (p = 0.08) increased in comparison to T0. A reduction in homocysteine from T0 to T1 (p = 0.01) was found. After 3 months, an increase in Rapid Assessment of Physical Activity tool 1 (RAPA) (p < 0.001) and RAPA 2 was observed (p = 0.009). We observed high levels of oxidative stress markers at baseline. After 6 months of MD, a significant improvement in lymphocyte Reactive Oxygen Species (ROS) (p < 0.001) and total antioxidant capacity was observed (p = 0.02). Conclusions: The improvement of lifestyle, and in particular the Mediterranean dietary intervention, allowed the improvement of the metabolic and oxidative profile and overall health-related quality of life

Atherosclerosis and Endometriosis: The Role of Diet and Oxidative Stress in a Gender-Specific Disorder

Background: Accelerated atherosclerosis in patients with endometriosis has been hypothesised, and lifestyle improvement might control cardiovascular risk. We explored cardiometabolic markers and oxidative stress and evaluated the effects of the Mediterranean Diet (MD) in modulating these markers. Methods: In this prospective study, we included 35 women with endometriosis. At baseline (T0) and after 3 (T1) and 6 (T2) months from the start of the diet, we investigated cardiometabolic parameters, lifestyle and oxidative stress. Results: After a 3-month intervention with MD, we observed a significant reduction in total cholesterol (p = 0.01) and LDL-c (p = 0.003). We observed at T1 an increase in B12 and E vitamins, folate and zinc. After 6 months, zinc (p = 0.04) and folate (p = 0.08) increased in comparison to T0. A reduction in homocysteine from T0 to T1 (p = 0.01) was found. After 3 months, an increase in Rapid Assessment of Physical Activity tool 1 (RAPA) (p p = 0.009). We observed high levels of oxidative stress markers at baseline. After 6 months of MD, a significant improvement in lymphocyte Reactive Oxygen Species (ROS) (p p = 0.02). Conclusions: The improvement of lifestyle, and in particular the Mediterranean dietary intervention, allowed the improvement of the metabolic and oxidative profile and overall health-related quality of life

Neutrophil-mediated mechanisms of damage and in vitro protective effect of colchicine in non-vascular Behçet's syndrome

Behçet’s syndrome (BS) is a systemic vasculitis with several clinical manifestations. Neutrophil hyperactivation mediates vascular BS pathogenesis, via both a massive reactive oxygen species (ROS) production and neutrophil extracellular traps (NETs) release. Here, we investigated neutrophil‐mediated mechanisms of damage in non‐vascular BS manifestations and explored the in‐vitro effects of colchicine in counteracting these mechanisms. NETs and intracellular ROS production was assessed in blood samples from 80 BS patients (46 with active non‐vascular BS, 34 with inactive disease) and 80 healthy controls. Moreover, isolated neutrophils were incubated for 1 h with an oxidating agent [2,2′‐azobis (2‐amidinopropane) dihydrochloride; 250 nM] and the ability of pure colchicine pretreatment (100 ng/ml) to counteract oxidation‐induced damage was assessed. Patients with active non‐vascular BS showed remarkably increased NET levels [21.2, interquartile range (IQR) = 18.3–25.9 mU/ml] compared to patients with inactive disease (16.8, IQR = 13.3–20.2 mU/ml) and to controls (7.1, IQR = 5.1–8.7 mU/ml, p < 0.001]. Also, intracellular ROS tended to increase in active BS, although not significantly. In active non‐vascular BS, NETs correlated with neutrophil ROS production (p < 0.001) and were particularly increased in patients with active mucosal (p < 0.001), articular (p = 0.004) and gastrointestinal symptoms (p = 0.006). In isolated neutrophils, colchicine significantly reduced oxidation‐induced NET production and cell apoptosis, although not via an anti‐oxidant activity. Neutrophil‐mediated mechanisms might be directly involved in non‐vascular BS, and NETs, more than ROS, might drive the pathogenesis of mucosal, articular and intestinal manifestations. Colchicine might be effective in counteracting neutrophils‐mediated damage in BS, although further studies are needed

Blood Leukocyte ROS Production Reflects Seminal Fluid Oxidative Stress and Spermatozoa Dysfunction in Idiopathic Infertile Men

A large proportion of infertile men do not receive a clear diagnosis, being considered as idiopathic or unexplained cases due to infertility diagnosis based on standard semen parameters. Particularly in unexplained cases, the search for new indicators seems mandatory to provide specific information. In the etiopathogenesis of male infertility oxidative stress displays important roles by negatively affecting sperm quality and function. In this study, performed in a population of 34 idiopathic infertile men and in 52 age-matched controls, redox parameters were assessed in blood, leukocytes, spermatozoa, and seminal fluid and related to semen parameters. The main findings indicate that blood oxidative stress markers reflect seminal oxidative stress. Interestingly, blood leukocyte ROS production was significantly correlated to sperm ROS production and to semen parameters. Overall, these results suggest the potential employ of blood redox markers as a relevant and adjunctive tool for sperm quality evaluation aimed to preconception care