The role of antioxidants in the treatment of infertile men with varicocele

Varicocele is a common disease that occurs in 35–40% of men with primary infertility and in 80% of men with secondary infertility Disturbance of microcirculation in the testicles, which occurs during varicocele, lead to ischemia and hypoxia of the testicles, which provoke degenerative changes in all testicular cell populations. Retrograde blood flow from the testicular vein and the external spermatic vein into pampiniform venous plexus leads to an increase of hydrostatic pressure in the testicular vascular system and rise of temperature, and it also contributes to the development of sterile inflammation. Oxidative stress, nitrosative stress, and hypoxia are generally recognized elements of the pathogenesis of infertility associated with varicocele. It is known that when the supraphysiological level of reactive oxygen species in the ejaculate is reached, their concentration disrupts the structure and function of spermatozoa. Nitric oxide (NO) is involved in the regulation of body temperature, NO-dependent mechanisms may contribute to the increased scrotal temperature during varicocele. The physiological concentration of NO pro duced by testicular macrophages stimulates steroidogenesis in Leydig cells. However, in the presence of certain reactive oxygen species, NO can transform into peroxynitrite and other strong cytotoxic metabolites, which lead to dysregulation of testosterone synthesis involved in spermatogenesis. Also, manifestations of varicocele among infertile men have decreased expression levels of the testis-specific heat-shock protein, HSPA2, and abnormal methylation of sperm DNA. Therefore, the use of combined anti oxidant supplements as part of adjuvant therapy after surgical treatment or as an independent application in some clinical cases appears to be an adequate strategy to optimize fertility in patients with varicocele. In this review, we evaluated the importance of various antioxidants, such as vitamin E, folic acid, carnitine, inositol, arginine, acetylcysteine, zinc, selenium in spermatogenesis and their effect on reproductive function during varicocele.

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Stimulated Reactive Oxygen Species Generation in the Spermatozoa of Infertile Men

The Journal of Urology ◽

10.1016/s0022-5347(17)36000-7 ◽

1993 ◽

Vol 149 (1) ◽

pp. 64-67 ◽

Cited By ~ 46

Author(s):

Donald L. Weese ◽

Michael L. Peaster ◽

Kyle K. Himsl ◽

Gary E. Leach ◽

Pramod M. Lad ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Infertile Men

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Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber’s Hereditary Optic Neuropathy Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/3187560 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Micol Falabella ◽

Elena Forte ◽

Maria Chiara Magnifico ◽

Paolo Santini ◽

Marzia Arese ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Optic Neuropathy ◽

Nitrosative Stress ◽

Mononuclear Cells ◽

Reactive Oxygen ◽

Leber’S Hereditary Optic Neuropathy ◽

Oxygen Species ◽

Nitrogen Species ◽

Leber's Hereditary Optic Neuropathy ◽

Hereditary Optic Neuropathy

Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber’s hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment.

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Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence

The Journal of Cell Biology ◽

10.1083/jcb.200706072 ◽

2008 ◽

Vol 180 (1) ◽

pp. 101-112 ◽

Cited By ~ 132

Author(s):

Michael Schleicher ◽

Benjamin R. Shepherd ◽

Yajaira Suarez ◽

Carlos Fernandez-Hernando ◽

Jun Yu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Endothelial Cells ◽

Mitochondrial Function ◽

Vascular System ◽

Reactive Oxygen ◽

Direct Consequence ◽

Oxygen Species ◽

Inner Mitochondrial Membrane ◽

Prohibitin 1

Prohibitin 1 (PHB1) is a highly conserved protein that is mainly localized to the inner mitochondrial membrane and has been implicated in regulating mitochondrial function in yeast. Because mitochondria are emerging as an important regulator of vascular homeostasis, we examined PHB1 function in endothelial cells. PHB1 is highly expressed in the vascular system and knockdown of PHB1 in endothelial cells increases mitochondrial production of reactive oxygen species via inhibition of complex I, which results in cellular senescence. As a direct consequence, both Akt and Rac1 are hyperactivated, leading to cytoskeletal rearrangements and decreased endothelial cell motility, e.g., migration and tube formation. This is also reflected in an in vivo angiogenesis assay, where silencing of PHB1 blocks the formation of functional blood vessels. Collectively, our results provide evidence that PHB1 is important for mitochondrial function and prevents reactive oxygen species–induced senescence and thereby maintains the angiogenic capacity of endothelial cells.

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On the Origin and Fate of Reactive Oxygen Species in Plant Cell Compartments

Antioxidants ◽

10.3390/antiox8040105 ◽

2019 ◽

Vol 8 (4) ◽

pp. 105 ◽

Cited By ~ 32

Author(s):

Janků ◽

Luhová ◽

Petřivalský

Keyword(s):

Reactive Oxygen Species ◽

Plant Cell ◽

Nitrosative Stress ◽

Reactive Oxygen ◽

Redox Status ◽

Stress Conditions ◽

Ros Generation ◽

Oxygen Species ◽

Ros Scavenging ◽

Cell Compartments

Reactive oxygen species (ROS) have been recognized as important signaling compoundsof major importance in a number of developmental and physiological processes in plants. Theexistence of cellular compartments enables efficient redox compartmentalization and ensuresproper functioning of ROS‐dependent signaling pathways. Similar to other organisms, theproduction of individual ROS in plant cells is highly localized and regulated bycompartment‐specific enzyme pathways on transcriptional and post‐translational level. ROSmetabolism and signaling in specific compartments are greatly affected by their chemicalinteractions with other reactive radical species, ROS scavengers and antioxidant enzymes. Adysregulation of the redox status, as a consequence of induced ROS generation or decreasedcapacity of their removal, occurs in plants exposed to diverse stress conditions. During stresscondition, strong induction of ROS‐generating systems or attenuated ROS scavenging can lead tooxidative or nitrosative stress conditions, associated with potential damaging modifications of cellbiomolecules. Here, we present an overview of compartment‐specific pathways of ROS productionand degradation and mechanisms of ROS homeostasis control within plant cell compartments.

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Levels of seminal reactive oxygen species (ROS) are highly correlated with apoptosis in ejaculated spermatozoa from infertile men

Fertility and Sterility ◽

10.1016/s0015-0282(02)03837-2 ◽

2002 ◽

Vol 78 ◽

pp. S167

Author(s):

Mohamed H Moustafa ◽

Ramadan A Saleh ◽

Mehmet Oder ◽

Rakesh K Sharma ◽

Mohammed A Abdel-Hafez ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Oxygen Species ◽

Infertile Men ◽

Highly Correlated

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Defining the reference value of seminal reactive oxygen species in a population of infertile men and normal healthy volunteers

Fertility and Sterility ◽

10.1016/j.fertnstert.2007.07.1025 ◽

2007 ◽

Vol 88 ◽

pp. S305 ◽

Cited By ~ 10

Author(s):

M. Bykova ◽

K. Athayde ◽

R. Sharma ◽

R. Jha ◽

E. Sabanegh ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Healthy Volunteers ◽

Reactive Oxygen ◽

Reference Value ◽

Oxygen Species ◽

Infertile Men

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Impact of Lead on Reproductive Health of Men

Ukraïnsʹkij žurnal medicini bìologìï ta sportu ◽

10.26693/jmbs06.04.193 ◽

2021 ◽

Vol 6 (4) ◽

pp. 193-198

Author(s):

S. S. Ostrovska ◽

◽

V. F. Shatorna ◽

O. G. Slesarenko ◽

P. G. Gerasymchuk ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Male Infertility ◽

Reactive Oxygen ◽

Reproductive Function ◽

Hormonal Control ◽

The Body ◽

Toxic Effects ◽

Seminiferous Tubules ◽

Oxygen Species ◽

The Impact

Lead does not succumb to biological decomposition, and its ability to accumulate in the body makes it a serious threat to the health of people and animals, while affecting the reproductive function. In most cases, poisoning with lead remains asymptomatic. In a number of studies the authors concluded that in men the level of lead in the blood more than >40 μg/dL leads to the disorder of reproductive functions, such as low libido, a small sperm volume, the amount of spermatozoa, an increase in the abnormal morphology of spermatozoa and decrease in their motility. Male factors are considered the main cause of infertility in 40% of infertile couples and contribute to the emergence of this state in combination with female factors in 20% of cases. The mechanisms of how lead causes male infertility are covered in depth. It is assumed that the basic effect on the reproductive function of men is likely to occur due to changes in the reproductive hormonal axis and hormonal control of spermatogenesis, and not due to direct toxic effects on the seminiferous tubules. The adverse effect of lead on the male reproductive function, especially at low doses (<10 μg/dl), has not been studied properly yet. The risk of lead poisoning is directly connected not only with an increase in concentration, but also with the duration of the impact of metal. There are a number of possible ways of how exposure of lead reduces male fertility. Lead, most likely, impairs the endocrine profile of regulation, mainly through the axis of the hypothalamus-pituitary testosterone, hereafter reduces the production of sperm in the seminiferous tubules of the testicles. At the same time, it acts as an endocrine destroyer, affecting hormones responsible for the production of sperm. In addition to changes in the reproductive hormone axis and hormonal control of spermatogenesis, the activity of enzymes, such as alkaline phosphatase and potassium-sodium ATP-ase, direct toxic effects on the seminiferous tubules, the exposure time of the metal and its dose affect male infertility. Another problem associated with the reproductive toxicity of lead is determined by the excessive generation of the reactive oxygen species. It is known that the oxidative stress caused by lead is involved in the abnormal functions of spermatozoa and male infertility. The possibility to decrease lead level in the body using a number of methods, such as chelatotherapy, nano-encapsulation, use of N-acetylcysteine is considered. Conclusion. Based on animal studies, it seems to be rational to prescribe the corresponding antioxidants to persons suffering from abnormal parameters of spermatozoa and infertility due to the effects of lead. Antioxidants showed a protective effect on spermatogenesis on animal models and reduced reactive oxygen species in sperm and DNA fragmentation in studies in humans. Although there is no final evidence confirming the use of antioxidant additives in men with low fertility to improve fertility rates, it is believed that due to the low cost and a small number of side effects, antioxidants need to be recommended to men with insufficient fertility

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