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Background: Semen hyperviscosity is a threatening cause of abnormal spermatozoa and infertility in men. We aimed to evaluate oxidative stress, antioxidants depletion and sperm apoptosis as main reasons for poor quality of spermatozoa in men with hyperviscous semen. Materials and Methods: In this cross-sectional study, ejaculate specimens were collected from fertile (n=102) and infertile men with hyperviscous semen (n=123) and without semen hyperviscosity (n=143). Total antioxidant capacity (TAC), glutathione (GSH), malondialdehyde (MDA), protein carbonyl (PC), 8-hydroxydeoxyguanosine (8-OHdG), and were measured in semen samples to estimate oxidative stress status. Gene expression pattern of BAX, CASPASE-9, CASPASE-3, and BCL2 was assessed to estimate sperm apoptosis. Results: The average of sperm count, normal morphology, normal motility, and sperm vitality in men with hyperviscous semen was significantly lower than infertile subjects without hyperviscous semen (P<0.01). Men with hyperviscous semen exhibited higher levels of PC (8.34 ± 1.03 nmol/mg vs. 6.01 ± 0.93 nmol/mg, P=0.008), MDA (1.14 ± 0.27 nmol/ ml vs. 0.89 ± 0.22 nmol/ml, P=0.031), 8-OHdG (259.71 ± 24.59 ng/ml vs. 197.13 ± 18.47 ng/ml, P=0.009), but lower TAC contents (1250.44 ± 66.23 μM/L vs. 1784.31 ± 89.87 μM/L, P=0.018) and GSH (3.82 ± 1.05 μM vs. 5.89 ± 0.87 μM, P=0.021) than men with non-viscous semen. The expression of BAX, CASPASE-3 and CASPASE-9 genes in men with hyperviscous semen was significantly increased by 1.39-fold (P=0.041), 1.47-fold (P=0.046), 1.29-fold (P=0.048), respectively, as compared with the infertile subjects without hyperviscous semen. However, BCL2 expression in infertile men without hyperviscous semen was higher compared to those with hyperviscous semen (1.36-fold, P=0.044). Conclusion: Hyperviscous semen is markedly associated with depletion of seminal plasma antioxidants, sperm membrane lipid peroxidation, DNA and protein oxidation, and sperm apoptosis. Antioxidant therapy might be considered as a valuable strategy to protect sperm cells against oxidative damage in cases with seminal fluid hyperviscosity. [ABSTRACT FROM AUTHOR]

Aging is a natural process coupled with oxidative stress and chronic inflammation, gradually associated with losing organ function over time. Therefore, the objective of the current work was to peruse the protective effects of 8-week moderate-intensity interval training (MIIT) and ginger extract supplementation on some biomarkers of oxidative stress, inflammation, and lipid metabolism in the liver of elderly males Wistar rats (animal study with ethical code IR.BMSU.REC.1401.015). A total of thirty-two 22-month-aged male Wistar rats were randomly assigned to four groups: (1) control, (2) MIIT, (3) ginger, and (4) MIIT + ginger. After 8 weeks of treadmill training and ginger extract supplementation, the biochemical parameters (liver enzyme and lipid profile), inflammatory mediators (leucine-rich α-2 glycoprotein 1 (LRG1), tumor necrosis factor-alpha, and interleukin-6), pro-oxidant (malondialdehyde), antioxidant biomarkers (catalase, superoxide dismutase, total antioxidant capacity), some lipid metabolism regulators (carnitine palmitoyltransferase 1, adipose triglyceride lipase, acetyl-CoA carboxylase, CD36, and AMP-activated protein kinase), and liver histopathological changes were appraised. The acquired findings pointed out that MIIT combined with ginger extract appreciably diminished the serum levels of LRG1, liver enzymes, and lipid profile relative to the other groups after 8 weeks of intervention. Furthermore, ginger + MIIT caused a great improvement in the liver levels of antioxidant biomarkers, pro-oxidant, pro-inflammatory biomarkers, lipid metabolism regulators, and liver tissue impairment compared to the other groups. The findings suggested that MIIT + ginger was more effective in improving examined indices relative to the other groups. [ABSTRACT FROM AUTHOR]

Sulfur mustard (SM) is an alkylating and forming chemical that was widely used by Iraqi forces during the Iran–Iraq wars. One of the target organs of SM is the skin. Understanding the mechanisms involved in the pathogenesis of SM may help better identify complications and find appropriate treatments. The current study collected ten SM-exposed patients with long-term skin complications and ten healthy individuals. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the skin protein profile, and statistical bioinformatics methods were used to identify the differentially expressed proteins. One hundred twenty-nine proteins had different expressions between the two groups. Of these 129 proteins, 94 proteins had increased expression in veterans' skins, while the remaining 35 had decreased expression. The hub genes included RPS15, ACTN1, FLNA, HP, SDHC, and RPL29, and three modules were extracted from the PPI network analysis. Skin SM exposure can lead to oxidative stress, inflammation, apoptosis, and cell proliferation. [ABSTRACT FROM AUTHOR]

Zinc (Zn) is necessary for the normal function of the male reproductive system and spermatozoa. Although influences of zinc deficiency on impaired spermatogenesis and male infertility have been widely considered, the molecular and cellular mechanisms of these abnormalities are not well understood. General abnormalities, including hypogonadism, Leydig cells damage, deficiency of sex hormone production and impaired spermatogenesis, as well as inflammation, antioxidant depletion, sperm death and male infertility can be observed during zinc deficiency. However, it is not obvious which pathways are relevant to the pathogenesis of zinc deficiency. Oxidative stress (OS) induced by reactive oxygen species is likely as the main mechanism of zinc deficiency which is associated with sperm DNA fragmentation, decrease in sperm membrane integrity, apoptosis, depletion of antioxidants, and consequently poor sperm quality and male infertility. Therefore, identification of these pathways will give valuable information regarding the mechanisms of zinc deficiency on the male reproductive system and the potential way for developing a better clinical approach. In this review, we aim to discuss the proposed cellular and molecular mechanisms of zinc deficiency on the male reproductive system, the importance of OS and mechanisms by which zinc deficiency induces OS and depletion of other antioxidants. [ABSTRACT FROM AUTHOR]

Dysregulation of matrix metalloproteinases (MMPs) is now considered as one of the main toxicity effects of sulfur mustard (SM). Numerous studies have found overexpression of MMPs, but the mechanism is unclear. Accumulation of leukocytes, downregulation of tissue inhibitors of metalloproteinases (TIMPs), increase of pro-inflammatory mediators, as well as massive production of reactive oxygen species (ROS) and oxidative stress (OS) are possible mechanisms by which SM induces MMPs expression long-years after exposure. We aim to discuss cellular and molecular mechanisms of SM toxicity, the importance of MMPs and mechanisms by which SM enhances expression of these proteases in SM-victims. [ABSTRACT FROM AUTHOR]

Sulfur mustard (SM) is a chemical compound that preferentially targets ocular, cutaneous and pulmonary tissues. Although pathologic effect of SM has been extensively considered, molecular and cellular mechanism of its toxicity, especially at the chronic phase of injury is not well-understood. Excessive production of reactive oxygen species (ROS) and oxidative stress (OS) appears to be involved in SM-induced injuries. SM may trigger several molecular and cellular pathways linked to OS and inflammation that can subsequently result in cell death and apoptosis. At the acute phase of injury, SM can enhance ROS production and OS by reducing the activity of antioxidants, depletion of intercellular glutathione (GSH), decreasing the productivity of GSH-dependent antioxidants, mitochondrial deficiency, accumulation of leukocytes and pro-inflammatory cytokines. Overexpression of ROS producing enzymes and down-regulation of antioxidant enzymes are probably the major events by which SM leads to OS at the chronic phase of injury. Therefore, antioxidant therapy with potent antioxidants such as N-acetylcysteine and curcumin may be helpful to mitigate SM-induced OS damages. This review aims to discuss the proposed cellular and molecular mechanisms of acute and delayed SM toxicity, the importance of OS and mechanisms by which SM increases OS either at the acute or chronic phases of injuries along with research on antioxidant therapy as a suitable antidote. [ABSTRACT FROM AUTHOR]

Sulfur mustard (SM) is a mutagenic compound that targets various organs. Although it causes a wide range of abnormalities, cellular and molecular mechanisms of its action are not-well-understood. Oxidation of DNA, proteins, lipids, as well as depletion of cellular nicotinamide adenine dinucleotide (NAD), antioxidants and increase of intracellular calcium are the hypothesized mechanisms of its action at the acute phase of injury. In this review, the proteome analysis of SM toxicity has been considered. We selected articles that considered proteomics analysis of SM toxicity with two-dimensional gel electrophoresis (2DE) followed by mass spectrometry. Our search yielded nine related articles, four original in vitro and five human studies. The results of these studies have revealed a change in expression pattern of various proteins such as haptoglobin, amyloid A1, surfactant proteins, S100 proteins, apolipoprotein, Vit D binding protein, transferrin, alpha 1 antitrypsin, protein disulfide isomerase and antioxidant enzymes in patients who were exposed to SM about 30 years ago. Most of these proteins are up- or down-regulated in response to excessive production of reactive oxygen species (ROS) and oxidative stress (OS). There is a tight link between the expression pattern of these proteins with accumulation of leukocytes, inflammatory conditions, antioxidant depletion, mitochondrial deficiency, as well as increased expression or activity of several proteases such as caspases and matrix metalloproteinases (MMPs). Therefore, excessive production of ROS and OS along with chronic inflammatory may be the long-term toxic effects of SM following acute exposure. [ABSTRACT FROM AUTHOR]

Diazinon (DZN) is an organophosphate insecticide that has cytotoxic and pathological effects on the reproductive system. It causes a wide variety of pathological effects on the reproductive system such as testicular atrophy, disturbance in sex hormones, impaired spermatogenesis, low quality of sperm, and fertility problems. However, molecular and cellular mechanisms of its adverse effects are not well understood. General events such as testicular damage, inflammation, mitochondrial deficiency, DNA fragmentation, disintegration of sperm plasma membrane, apoptosis, and cell death are observed in DZN-exposed animals. Oxidative stress (OS) induced by reactive oxygen species may be a main mechanism, which can be associated with sperm DNA fragmentation, reduced integrity of sperm cell membrane, apoptosis, depletion of antioxidants, and subsequently poor sperm quality and male infertility. Therefore, identification of these pathways may provide valuable information regarding the mechanisms of DZN action on the male reproductive system. In this review, we aim to discuss the proposed cellular and molecular mechanisms of DZN action on male reproductive system, the importance of OS and mechanisms by which DZN induces OS and depletion of other antioxidants. [ABSTRACT FROM AUTHOR]

Context: Sulfur mustard (SM) is a lipophilic and reactive chemical compound that targets human airway system. Objective: Glutathione (GSH) depletion, oxidative stress (OS) status, and changes in expression of GSH-dependent antioxidant enzymes were considered in human mustard lungs. Materials and methods: Lung biopsies and bronchoalveolar lavage (BAL) were collected from non-exposed (n = 10) individuals and SM-exposed patients (n = 12). Alterations in expression of GSH-dependent enzymes were studied using RT2 Profiler™ PCR array. OS was evaluated by determining BAL fluid levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and GSH. Results: Mean TAC (0.142 ± 0.027 µmol/l) and GSH (4.98 ± 1.02 nmol/l) in BAL fluids of control group was significantly higher (p < .05) than those in SM-exposed patients (TAC = 0.095 ± 0.018 µmol/l and GSH= 3.09 ± 1.02 nmol/l), while MDA level in BAL fluids of these patients (0.71 ± 0.06 nmol/l) was significantly (p = .001) higher than that in controls (0.49 ± 0.048 nmol/l). Glutathione peroxidases (GPXs), glutathione-s-transferases (GSTs), and glutathione synthetase (GSS) enzymes were overexpressed in mustard lung biopsies, while glutathione reductase (GSR) was significantly downregulated (14.95-fold). Conclusions: GSH depletion induced by GSR downregulation may be a major mechanism of SM toxicity on human lung. Despite overexpression of GSTs and GPXs genes, GSH depletion may decline the productivity of these enzymes and total antioxidants capacity, which is associated with OS. [ABSTRACT FROM AUTHOR]

Sulfur mustard (SM) is a chemical alkylating compound that primary targets lung tissue. It causes a wide variety of pathological effects in respiratory system such as chronic bronchitis, bronchiolitis obliterans, necrosis of the mucosa and inflammation, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. However, molecular and cellular mechanisms for these pathologies are still unclear. Oxidative stress (OS) induced by reactive oxygen species (ROS) is likely a significant mechanism by which SM leads to cell death and tissues injury. SM can trigger various molecular and cellular pathways that are linked to ROS generation, OS, and inflammation. Hypoxia-induced oxidative stress, reduced activity of enzymatic antioxidants, depletion of intercellular glutathione (GSH), decreased productivity of GSH-dependent antioxidants, mitochondrial dysfunction, accumulation of leukocytes and proinflammatory cytokines, and increased expression of ROS producing-related enzymes and inflammatory mediators are the major events in which SM leads to massive production of ROS and OS in pulmonary system. Therefore, understanding of these molecules and signaling pathways gives us valuable information about toxicological effects of SM on injured tissues and the way for developing a suitable clinical treatment. In this review, we aim to discuss the possible mechanisms by which SM induces excessive production of ROS, OS, and antioxidants depletion in lung tissue of exposed patients. [ABSTRACT FROM AUTHOR]