Administration of Antioxidants in the Infertile Male: When it may have a Beneficial Effect?.

Background: Reactive Oxygen Species (ROS) are required for intact spermatogenesis and sperm function, but excessive levels will cause oxidative stress, impairing sperms and sperm function due to membrane damage and DNA fragmentation. Objective: Theoretically, antioxidant supplementation may act as a protecting system against free radicals. Since infertile males have higher levels of ROS, nutritional supplements are widely used for protecting sperms. In the recent review authors summarize the most recent data regarding the effect of antioxidant treatment and draw an attention of the limitations of antioxidant use in male infertility. Methods: The recent review gives an update of antioxidant treatment in male infertility. Results: Improvement of sperm parameters was reported in the majority of studies. Comparing different antioxidants versus placebo showed low certainty of evidence with a serious risk of bias, and there is a lack regarding certain doses, pregnancy rate, and live birth rate outcomes. Various clinical studies and randomized control trials reported even negative outcomes. Conflicting findings lead the attention to the study of biochemical features of the oxidant vs. antioxidant equilibrium. Higher exposure to antioxidants will result in „reductive stress”, which has harmful effects on sperm function, moreover can negatively influence embryo development. Reductive stress is as dangerous as oxidative stress and may act as a cause of different human pathologies. Conclusion: An intact balance of oxidant and antioxidant systems is required to normal sperm function. No guideline exists for the antioxidant dose regimen and treatment duration. Overdosing can result in reductive stress, which is also harmful to fertility and can cause several diseases. Assessment of the pre-treatment redox status can be recommended before the administration of exogenous antioxidants.

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Exercise-Induced Reductive Stress Is a Protective Mechanism against Oxidative Stress in Peripheral Blood Mononuclear Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/3053704 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Ypatios Spanidis ◽

Aristidis S. Veskoukis ◽

Christina Papanikolaou ◽

Dimitrios Stagos ◽

Alexandros Priftis ◽

...

Keyword(s):

Oxidative Stress ◽

Eccentric Exercise ◽

Mononuclear Cells ◽

Reductive Group ◽

Redox Status ◽

Protective Mechanism ◽

Peripheral Blood Mononuclear ◽

Reductive Stress ◽

Blood Mononuclear Cells ◽

Baseline Values

Eccentric exercise is a well-studied modality that induces oxidative stress and muscle damage. Furthermore, it promotes inflammatory response in which peripheral blood mononuclear cells (PBMCs) are the major mediators. Although free radicals are necessary in a specific range of concentrations, yet unknown, it remains unclear whether reductive redox status (i.e., increased antioxidant defenses and impaired free radical generation) is beneficial or not. Thus, the aim of the present investigation was to examine the effects of reductive stress and the impact of reduced glutathione (GSH) baseline values on the ability of PBMCs to counteract oxidative stress induced by a potent oxidative agent. PBMCs were isolated from the blood of subjects who performed eccentric exercise and treated with t-BOOH for 24 h. The subjects were clustered in the reductive and the oxidative group on the basis of increased or decreased GSH concentration postexercise compared to preexercise values, respectively. According to our results in PBMCs, lipid peroxidation levels as depicted by thiobarbituric acid reactive substances (TBARS) remained unchanged in the reductive group contrary to the observed enhancement in the oxidative group. In addition, GSH concentration and catalase activity increased in the reductive group, whereas they were not affected in the oxidative group. In conclusion, the effects of an oxidizing agent on the redox status of PBMCs isolated from the blood of athletes after acute eccentric exercise are dependent on the baseline values of GSH in erythrocytes. Otherwise, reductive stress defined by increased GSH levels is a protective mechanism, at least when followed by an oxidative stimulus.

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Salivary Biomarkers of Oxidative Stress in Children with Chronic Kidney Disease

Journal of Clinical Medicine ◽

10.3390/jcm7080209 ◽

2018 ◽

Vol 7 (8) ◽

pp. 209 ◽

Cited By ~ 43

Author(s):

Mateusz Maciejczyk ◽

Julita Szulimowska ◽

Anna Skutnik ◽

Katarzyna Taranta-Janusz ◽

Anna Wasilewska ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Oxidative Damage ◽

Diagnostic Value ◽

Redox Status ◽

Stress Index ◽

Antioxidant Systems ◽

Control Group ◽

Potential Biomarker

There are still missing non-invasive biomarkers of chronic kidney disease (CKD) in children. Therefore, the aim of the study was to evaluate oxidative stress indicators in the non-stimulated (NWS) and stimulated saliva (SWS) of CKD children (n = 25) and healthy controls (n = 25). Salivary antioxidants (catalase (CAT), peroxidase (Px), superoxide dismutase (SOD), uric acid (UA), reduced glutathione (GSH), albumin), redox status (total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA)) were evaluated. We have demonstrated the significantly higher activity of SWS GPx and SOD, as well as elevated concentrations of UA and albumin in NWS and SWS of CKD children vs. the control group. TAC, TOS and OSI were significantly higher only in SWS, while oxidative damage products (AGE, AOPP and MDA) were significantly higher in both NWS and SWS of CKD children. ROC analysis showed a considerably high diagnostic value of AOPP in both NWS and SWS of CKD children compared to controls (AUC = 0.92; 0.98). CKD is responsible for disturbances in salivary antioxidant systems and oxidative damage to proteins and lipids. Salivary AOPP can be a potential biomarker of CKD in children.

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Elevated DNA Damage, Oxidative Stress, and Impaired Response Defense System Inflicted in Patients With Myocardial Infarction

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029617725602 ◽

2017 ◽

Vol 24 (5) ◽

pp. 780-789 ◽

Cited By ~ 6

Author(s):

Sumayya Shahzad ◽

Asif Hasan ◽

Abul Faiz Faizy ◽

Somaiya Mateen ◽

Naureen Fatima ◽

...

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Myocardial Infarction ◽

Membrane Damage ◽

Redox Status ◽

Antioxidant Potential ◽

Total Antioxidant ◽

Coronary Events ◽

Grace Score ◽

Score Risk

Background: Ischemic tissue damage in myocardial infarction (MI) is allied with the exaggerated production of reactive oxygen species (ROS) beyond the countering capability of chain-breaking radical scavengers, fallouts in the form of oxidatively burdened myocardial tissue. Methods: One hundred and twenty five patients with MI were included in the study to evaluate the dynamics of redox status of patients by monitoring the antioxidant potential, biomarkers of oxidative stress, lipid indices, RBC membrane damage when compared to healthy individuals in patients with MI congregated on the basis of Global Registry of Acute Coronary Events (GRACE) score, risk factors, and age. Results: Higher levels of malondialdehyde, 8-hydroxy-2-deoxyguanosine, lipid indices, ROS content, and membrane deterioration in erythrocytes were seen in patients with MI. Furthermore, reduced activities of erythrocyte antioxidant enzymes and lower concentrations of antioxidant molecules, plus reduced total antioxidant capacity, were observed in plasma of all patients with MI with respect to control. However, elevation in oxidative stress was found to be significantly marked in patients having GRACE score >100, risk factors, and MI >45 years when compared to patients with GRACE score ≤100, without risk factors, and MI ≤45 years, respectively. Conclusion: These findings indicate the existence of increased oxidative damage and reduced antioxidant potential in patients with MI have a potent relationship with their GRACE risk score, risk factors, and age.

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OXIDATIVE STRESS TESTING AND ANTIOXIDANT TREATMENT OF MALE INFERTILITY – SURVEY OF CURRENT CLINICAL PRACTICES

Fertility and Sterility ◽

10.1016/j.fertnstert.2021.07.920 ◽

2021 ◽

Vol 116 (3) ◽

pp. e342

Author(s):

Ashok Agarwal ◽

Renata Finelli ◽

Ralf Henkel ◽

Ramadan Saleh ◽

Rupin Shah

Keyword(s):

Oxidative Stress ◽

Male Infertility ◽

Stress Testing ◽

Clinical Practices ◽

Antioxidant Treatment

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Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Antioxidants ◽

10.3390/antiox10040510 ◽

2021 ◽

Vol 10 (4) ◽

pp. 510

Author(s):

Giuseppina Barrera ◽

Marie Angele Cucci ◽

Margherita Grattarola ◽

Chiara Dianzani ◽

Giuliana Muzio ◽

...

Keyword(s):

Oxidative Stress ◽

Transcription Factors ◽

Targeted Therapy ◽

Cancer Cells ◽

Antioxidant Response ◽

Redox Status ◽

Antioxidant Systems ◽

Drug Induced ◽

Transcriptional Coactivators ◽

Metabolic Remodeling

Chemoresistance represents the main obstacle to cancer treatment with both conventional and targeted therapy. Beyond specific molecular alterations, which can lead to targeted therapy, metabolic remodeling, including the control of redox status, plays an important role in cancer cell survival following therapy. Although cancer cells generally have a high basal reactive oxygen species (ROS) level, which makes them more susceptible than normal cells to a further increase of ROS, chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxidative stress by upregulating their antioxidant systems. The antioxidant response is principally mediated by the transcription factor Nrf2, which has been considered the master regulator of antioxidant and cytoprotective genes. Nrf2 expression is often increased in several types of chemoresistant cancer cells, and its expression is mediated by diverse mechanisms. In addition to Nrf2, other transcription factors and transcriptional coactivators can participate to maintain the high antioxidant levels in chemo and radio-resistant cancer cells. The control of expression and function of these molecules has been recently deepened to identify which of these could be used as a new therapeutic target in the treatment of tumors resistant to conventional therapy. In this review, we report the more recent advances in the study of Nrf2 regulation in chemoresistant cancers and the role played by other transcription factors and transcriptional coactivators in the control of antioxidant responses in chemoresistant cancer cells.

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Carnosine Protects Macrophages against the Toxicity of Aβ1-42 Oligomers by Decreasing Oxidative Stress

Biomedicines ◽

10.3390/biomedicines9050477 ◽

2021 ◽

Vol 9 (5) ◽

pp. 477

Author(s):

Giuseppe Caruso ◽

Cristina Benatti ◽

Nicolò Musso ◽

Claudia G. Fresta ◽

Annamaria Fidilio ◽

...

Keyword(s):

Oxidative Stress ◽

Therapeutic Potential ◽

Radical Scavenging ◽

Antioxidant Systems ◽

Trypan Blue Exclusion ◽

New Findings ◽

Pre Treatment ◽

The Brain

Carnosine (β-alanyl-L-histidine) is a naturally occurring endogenous peptide widely distributed in excitable tissues such as the brain. This dipeptide has well-known antioxidant, anti-inflammatory, and anti-aggregation activities, and it may be useful for treatment of neurodegenerative disorders such as Alzheimer’s disease (AD). In this disease, peripheral infiltrating macrophages play a substantial role in the clearance of amyloid beta (Aβ) peptides from the brain. Correspondingly, in patients suffering from AD, defects in the capacity of peripheral macrophages to engulf Aβ have been reported. The effects of carnosine on macrophages and oxidative stress associated with AD are consequently of substantial interest for drug discovery in this field. In the present work, a model of stress induced by Aβ1-42 oligomers was investigated using a combination of methods including trypan blue exclusion, microchip electrophoresis with laser-induced fluorescence, flow cytometry, fluorescence microscopy, and high-throughput quantitative real-time PCR. These assays were used to assess the ability of carnosine to protect macrophage cells, modulate oxidative stress, and profile the expression of genes related to inflammation and pro- and antioxidant systems. We found that pre-treatment of RAW 264.7 macrophages with carnosine counteracted cell death and apoptosis induced by Aβ1-42 oligomers by decreasing oxidative stress as measured by levels of intracellular nitric oxide (NO)/reactive oxygen species (ROS) and production of peroxynitrite. This protective activity of carnosine was not mediated by modulation of the canonical inflammatory pathway but instead can be explained by the well-known antioxidant and free-radical scavenging activities of carnosine, enhanced macrophage phagocytic activity, and the rescue of fractalkine receptor CX3CR1. These new findings obtained with macrophages challenged with Aβ1-42 oligomers, along with the well-known multimodal mechanism of action of carnosine in vitro and in vivo, substantiate the therapeutic potential of this dipeptide in the context of AD pathology.

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Influence of Oxidative Stress Generated by Smoking during Pregnancy on Glutathione Status in Mother-Newborn Pairs

Antioxidants ◽

10.3390/antiox10121866 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1866

Author(s):

Magdalena Chełchowska ◽

Joanna Gajewska ◽

Jadwiga Ambroszkiewicz ◽

Joanna Mazur ◽

Mariusz Ołtarzewski ◽

...

Keyword(s):

Oxidative Stress ◽

Cord Blood ◽

Tobacco Smoke ◽

Competitive Inhibition ◽

Redox Status ◽

Antioxidant Systems ◽

Smoking During Pregnancy ◽

Glutathione Status ◽

Immunoassay Technique ◽

Negative Effect

Glutathione plays a key role in maintaining a physiological balance between prooxidants and antioxidants in the human body. Therefore, we examined the influence of maternal smoking as a source of oxidative stress measured by total oxidant capacity (TOC) on reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GPx-3), and reductase (GR) amount in maternal and umbilical cord blood in 110 (45 smoking and 65 non-smoking) mother-newborn pairs. Concentrations of glutathione status markers and TOC were evaluated by competitive inhibition enzyme immunoassay technique. Plasma TOC levels were significantly higher and the GSH/GSSG ratio, which is considered an index of the cell’s redox status, were significantly lower in smoking women and their offspring than in non-smoking pairs. Decreased GR levels were found in smoking mothers and their newborns compared with similar non-smoking groups. Although plasma GPx-3 concentrations were similar in both maternal groups, in the cord blood of newborns exposed to tobacco smoke in utero they were reduced compared with the levels observed in children of tobacco abstinent mothers. Oxidative stress generated by tobacco smoke impairs glutathione homeostasis in both the mother and the newborn. The severity of oxidative processes in the mother co-existing with the reduced potential of antioxidant systems may have a negative effect on the oxidative-antioxidant balance in the newborn.

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Redox Balance in Male Infertility: Excellence through Moderation—“Μέτρον ἄριστον”

Antioxidants ◽

10.3390/antiox10101534 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1534

Author(s):

Evangelos N. Symeonidis ◽

Evangelini Evgeni ◽

Vasileios Palapelas ◽

Dimitra Koumasi ◽

Nikolaos Pyrgidis ◽

...

Keyword(s):

Oxidative Stress ◽

Male Infertility ◽

Medical Condition ◽

Wide Spectrum ◽

Semen Analysis ◽

Redox Balance ◽

Male Reproduction ◽

Specific Patient ◽

Reductive Stress ◽

The Impact

Male infertility, a relatively common and multifactorial medical condition, affects approximately 15% of couples globally. Based on WHO estimates, a staggering 190 million people struggle with this health condition, and male factor is the sole or contributing factor in roughly 20–50% of these cases. Nowadays, urologists are confronted with a wide spectrum of conditions ranging from the typical infertile male to more complex cases of either unexplained or idiopathic male infertility, requiring a specific patient-tailored diagnostic approach and management. Strikingly enough, no identifiable cause in routine workup can be found in 30% to 50% of infertile males. The medical term male oxidative stress infertility (MOSI) was recently coined to describe infertile men with abnormal sperm parameters and oxidative stress (OS), including those previously classified as having idiopathic infertility. OS is a critical component of male infertility, entailing an imbalance between reactive oxygen species (ROS) and antioxidants. ROS abundance has been implicated in sperm abnormalities, while the exact impact on fertilization and pregnancy has long been a subject of considerable debate. In an attempt to counteract the deleterious effects of OS, urologists resorted to antioxidant supplementation. Mounting evidence indicates that indiscriminate consumption of antioxidants has led in some cases to sperm cell damage through a reductive-stress-induced state. The “antioxidant paradox”, one of the biggest andrological challenges, remains a lurking danger that needs to be carefully avoided and thoroughly investigated. For that reason, oxidation-reduction potential (ORP) emerged as a viable ancillary tool to basic semen analysis, measuring the overall balance between oxidants and antioxidants (reductants). A novel biomarker, the Male infertility Oxidative System (MiOXSYS®), is a paradigm shift towards that goal, offering a quantification of OS via a quick, reliable, and reproducible measurement of the ORP. Moderation or “Μέτρον” according to the ancient Greeks is the key to successfully safeguarding redox balance, with MiOXSYS® earnestly claiming its position as a guarantor of homeostasis in the intracellular redox milieu. In the present paper, we aim to offer a narrative summary of evidence relevant to redox regulation in male reproduction, analyze the impact of OS and reductive stress on sperm function, and shed light on the “antioxidant paradox” phenomenon. Finally, we examine the most up-to-date scientific literature regarding ORP and its measurement by the recently developed MiOXSYS® assay.

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Research of indicators of pro- and antioxidant system in spermoplasm in violation of fertility in men

Urology ◽

10.26641/2307-5279.25.2.2021.238228 ◽

2021 ◽

Vol 25 (2) ◽

Author(s):

O.D. Melenevsky ◽

O.M. Chaika ◽

O.V. Tretyakova

Keyword(s):

Oxidative Stress ◽

Male Infertility ◽

Protection System ◽

Reproductive Age ◽

Antioxidant Systems ◽

Control Group ◽

Antioxidant Protection ◽

Study Results ◽

Mda Content ◽

Antioxidant Protection System

The article presents the study results of marker indicators of pro- and antioxidant spermoplasm systems among men of reproductive age with various types of infertility. It is shown that patients who were diagnosed with “secretory male infertility”, had the level of MDA content that was exceeding control indicators in 1.2 times (aЈ0,05) with simultaneous activation of SOD (in 132.2%, aЈ0,05) against the background of slight CAT activity decreasing. The SOD/CAT ratio increased in 1.44 times compared to the control, and the activity of GAOS enzymes was not significantly different from the control group. The condition of pro- and antioxidant protection system can be classified as “activated” due to “SOD + CAT” link with imbalance in the system, which can lead to progression of cytotoxic effects. The patients’ segmentation who were diagnosed with “excretory-toxic male infertility” into three subgroups by MDA content in spermoplasm made it possible to establish that the first subgroup was characterized by “compensatory activation” mainly of GAOS against the background of decreasing MDA content, in the second subgroup - indicators of the pro- and anti-radical protection system did not have reliable differences comparing with control results. The third subgroup showed increase of MDA content (66.1%, aЈ0,01) and activity decrease of all anti-radical protection systems. The state of pro- and antioxidant protection system in this subgroup can be classified as “oxidative stress.” The indicators study of pro-antioxidant systems in spermoplasm among patients with various types of male infertility will allow to carry out pathogenetically justified prevention and correction of conditions, which are accompanied by development of oxidative stress.

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Prm2 deficiency triggers a Reactive Oxygen Species (ROS)-mediated destruction cascade during epididymal sperm maturation in mice

10.1101/2020.05.05.075929 ◽

2020 ◽

Author(s):

Simon Schneider ◽

Farhad Shakeri ◽

Christian Trötschel ◽

Lena Arévalo ◽

Alexander Kruse ◽

...

Keyword(s):

Oxidative Stress ◽

Male Infertility ◽

Molecular Mechanisms ◽

Sperm Maturation ◽

Preimplantation Embryos ◽

Sperm Function ◽

Epididymal Sperm ◽

Small Proteins ◽

Infertile Men ◽

New Treatment

AbstractProtamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studies. Apart from impaired DNA integrity, protamine-deficient human and murine sperm show multiple secondary effects, including decreased motility and aberrant head morphology. In this study, we use a Prm2-deficient mouse model in combination with label-free quantitative proteomics to decipher the underlying molecular processes of these effects. We show that loss of the sperm’s antioxidant capacity, indicated by downregulation of key proteins like SOD1 and PRDX5, ultimately initiates an oxidative stress-mediated destruction cascade during epididymal sperm maturation. This is confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for oxidative stress-mediated DNA damage. Prm2-deficient testicular sperm are not affected and initiate the proper development of blastocyst stage preimplantation embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our results provide new insight into the role of Prm2 and its downstream molecular effects on sperm function and present an important contribution to the investigation of new treatment regimens for infertile men with impaired protamination.Significance statementSexual reproduction requires the successful fertilization of female eggs by male sperm. The generation of functional sperm is a complex, multi-step differentiation process known as spermatogenesis that takes places in the male testis. One important step for physiological sperm function is the incorporation of small proteins, known as protamines into the DNA. Defects within this process are common causes of male infertility. However, the underlying molecular mechanisms still remain largely unknown, thus preventing targeted therapies. Here, we identify the molecular cascade being initiated in protamine-deficient murine sperm that ultimately impedes fertilization. Our findings have broad implications for the development of new treatment options for infertile men with faulty protamination that seek medical advice.

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