Human seminal plasma is a natural reservoir of antioxidants that protect spermatozoa from oxidative damages. There is evidence in literature supports the fact that impairments in seminal antioxidant and lipid per-oxidation status play important roles in the physiopathology of male infertility. Our present study forms the first one which was carried out in Tunisia. We evaluated the antioxidant status in the seminal plasma of 120 infertile men programmed to In Vitro Fertilization (IVF) for the first tentative. Patients were characterized by an idiopathic infertility. They were divided into three groups: normozoospermics who were considered as controls (n=40), asthenozoospermics (Astheno; n=45) and oligoasthenoteratozoospermics (OAT; n=35). Seminal activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) and the levels of glutathione (GSH), zinc (Zn) and malondialdehyde (MDA) were measured. With the significant increase of the seminal activities of SOD and GPX in normozoospermics group, there were positive correlations observed between this enzymes and sperm quality. Also, significant elevated rates of seminal zinc and GSH were observed in control group, but there was contradictory associations reflecting the effects of these antioxidants on semen parameters. However, we noted significant increase of MDA levels in groups with abnormal seminogram. We showed negative associations between this per-oxidative marker and sperm parameters. These results obviously suggested that impairment on seminal antioxidants is an important risk factor for low sperm quality associated to idiopathic infertility and as a result can lead to poor IVF outcome.
Oxidative damage; Antioxidant enzymes; Semen quality; Male infertility; Sperm abnormalities; lipid per-oxidation.
It has been proposed that oxidative stress plays an important role in male infertility. The aims of this study were to compare seminal plasma levels of 15-F2t-isoprostane (8-iso-PGF2α), malondialdehyde (MDA), and total (sum of free and bound) homocysteine (tHcy) from normozoospermic vs. asthenozoospermic men, and to examine the relationships between tHcy and lipid peroxidation products. The study was a case-control study with a simple random sampling. The case group was consisted of 15 asthenozoospermic males. This group was compared with 15 normozoospermic men. Seminal plasma levels of 15-F2α-isoprostane and tHcy were measured using commercially available enzyme immunoassay (EIA) kits. MDA levels were determined by the thiobarbituric acid (TBA) assay. The Mann-Whitney U test was used to compare two groups. Coefficients of correlation were calculated using Spearman’s correlation analysis. All hypothesis tests were two-tailed with statistical significance assessed at the p value <0.05 level. MDA levels were higher in asthenozoospermic subjects than in control subjects (0.72±0.06 μM vs. 0.40±0.06 μM; p<0.05). No differences were seen in 15-F2α-isoprostane levels in asthenozoospermic subjects and controls (65.00±3.20 pg/ml vs. 58.17±4.12 pg/ml; p>0.05). Interestingly, tHcy levels were to be slightly higher in asthenozoospermic subjects than in controls (6.18±1.17 μM vs. 4.8±0.52 μM). Sperm motility was inversely correlated with seminal plasma 15-F2α-isoprostane and MDA levels, respectively (p<0.05). In summary, seminal plasma levels of 15-F2α-isoprostane and tHcy showed no significant difference between normozoospermic and asthenozoospermic men. Sperm motility was not correlated with seminal plasma levels of tHcy. No relationship was found between tHcy and lipid peroxidation.
15-F2α-isoprostane; Asthenozoospermia; Homocysteine; Lipid peroxidation; Malondialdehyde; Normozoospermia; Seminal plasma
Oxidative stress is a common pathology seen in approximately half of all infertile men. In a normal situation, the seminal plasma contains antioxidant mechanisms which are likely to quench these reactive oxygen species. However, during infertility complications these antioxidant mechanisms may downplay and create a situation which is called oxidative stress.
The aim of the present study was to assess the levels of lipid peroxide (LPO), protein peroxide (PPO) and activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX) in blood and semen samples of an infertile male population from North-East India.
We measured LPO, PPO, SOD and GPX in a total of 50 infertile individuals. For the study 20 fertile donors served as the control group.
Patients with male factor infertility had significantly higher LPO and PPO levels (60.84 ± 3.55 and 72.84 ± 3.66; P < 0.001) compared with controls (40.20 ± 4.33 and 59.93 ± 5.24) in blood. In semen also, the same trend was found with significantly higher LPO and PPO levels (200.27 ± 6.25 and 149.80 ± 11.47; P < 0.001) compared with controls (116.51 ± 5.49 and 59.10 ± 4.62). The SOD and GPX enzymes in blood (3.40 ± 1.06 and 0.16 ± 0.01; P < 0.001) and in semen (2.42 ± 1.32 and 0.24 ± 0.015; P < 0.001) showed a significantly lower activity when compared with their respective controls (4.85 ± 0.78; 0.36 ± 0.05 and 4.24 ± 0.89; 0.65 ± 0.03). The SOD and GPX activity when compared with the LPO and PPO values, showed a positive correlation.
We conclude that oxidative stress is associated with male factor infertility. This assessment may help in the treatment of this male infertility by suitable antioxidants.
Oxidative stress; Antioxidants; Male infertility; Reactive oxygen species
The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects.
It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry.
GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls.
This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages.
Zinc in human seminal plasma is divided into three types of ligands which are high (HMW), intermediate (IMW), and low molecular weight ligands (LMW). The present study was aimed to study the effect of Zn supplementation on the quantitative and qualitative characteristics of semen along with Zinc Binding Protein levels in the seminal plasma in asthenozoospermic patients.
Semen samples were obtained from 37 fertile and 37 asthenozoospermic infertile men with matched age. The subfertile group was treated with zinc sulfate, every participant took two capsules per day for three months (each one 220mg). Semen samples were obtained (before and after zinc sulfate supplementation). After liquefaction seminal fluid at room temperature, routine semen analyses were performed. For determination of the amount of zinc binding proteins, the gel filtration of seminal plasma on Sephadex G-75 was performed. All the fractions were investigated for protein and for zinc concentration by atomic absorption spectrophotometry. Evaluation of chromatograms was made directly from the zinc concentration in each fraction.
A significant high molecular weight zinc binding ligands percentage (HMW-Zn %) was observed in seminal plasma of fertile males compared with subfertile males. However, seminal low molecular weight ligands (LMW-Zn) have opposite behavior. The mean value of semen volume, progressive sperm motility percentage and total normal sperm count were increased after zinc sulfate supplementation.
Zinc supplementation restores HMW-Zn% in seminal plasma of asthenozoospermic subjects to normal value. Zinc supplementation elevates LMW-Zn% in seminal plasma of asthenozoospermic subjects to more than normal value.
ClinicalTrials.gov identifier NCT01612403
Zinc; Zinc binding protein; Gel filtration; Asthenozoospermia; Semenogelin
Infertility is an important medical and social problem that has an impact on well-being. A significant development in the last 10 years in the study of human infertility has been the discovery that oxidative sperm DNA damage has a critical role in the etiology of poor semen quality and male infertility. Selenium (Se) is an essential element for normal testicular development, spermatogenesis, and spermatozoa motility and function. The predominant biochemical action of Se in both humans and animals is to serve as an antioxidant via the Se-dependent enzyme glutathione peroxidase and thus protect cellular membranes and organelles from peroxidative damage. We explored the efficacy of Se in combination with vitamin E for improving semen parameters and pregnancy rates in infertile men.
Materials and methods
The study included 690 infertile men with idiopathic asthenoteratospermia who received supplemental daily Se (200 μg) in combination with vitamin E (400 units) for at least 100 days. The mean age of cases was 28.5 years (range 20–45), and the median age was 30 years. These cases had presented with male factor infertility (primary or secondary) for at least 1 year. The longest and shortest duration of infertility was 10 years and 1 year, respectively. The median time of diagnosis of infertility was 1 year with a mean of 2.5 years.
We observed 52.6% (362 cases) total improvement in sperm motility, morphology, or both, and 10.8% (75 cases) spontaneous pregnancy in comparison with no treatment (95% confidence interval: 3.08 to 5.52). No response to treatment occurred in 253 cases (36.6%) after 14 weeks of combination therapy. Mean difference between semen analyses of cases before and after treatment was 4.3% with a standard deviation of 4.29. On the basis of paired t-test results, combination therapy with oral Se and vitamin E was effective for treatment of asthenospermia or asthenoteratospermia or induction of spontaneous pregnancy (P ≤ 0.001).
Supplemental Se and vitamin E may improve semen quality and have beneficial and protective effects, especially on sperm motility. We advocate their use for the treatment of idiopathic male infertility diagnosed with asthenoteratospermia or asthenospermia in semen analysis.
asthenospermia; sperm; semen; teratospermia; infertility; male; selenium; vitamin E
Airway cellular dysfunction is a differentiating feature of severe asthma in children that may be related to an imbalance of the antioxidant, glutathione (GSH). We hypothesized that oxidation of GSH to glutathione disulfide (GSSG) in the epithelial lining fluid (ELF) of children with severe asthma would contribute to altered airway macrophage (AM) GSH homeostasis and AM cellular dysfunction. Bronchoalveolar lavage (BAL) was performed in 64 asthmatic children (severe asthma, n = 43). GSH, GSSG, markers of lipid peroxidation and DNA oxidation, and IL-8 were quantified in the BAL supernatant. GSH, GSSG, activities of histone deacetylase (HDAC) and histone acetyltransferase, apoptosis, and phagocytosis were assessed in isolated AMs. Children with severe asthma had increased GSSG, lipid peroxidation, byproducts of DNA oxidation, and inflammation in the ELF. This imbalance of GSH homeostasis was also noted intracellularly within the AMs and was associated with decreased HDAC activities, increased apoptosis, and impaired phagocytosis. In vitro GSH supplementation inhibited apoptosis and rescued phagocytosis in children with severe asthma. Severe asthma in children is characterized by altered airway and intracellular AM GSH homeostasis that translates to impaired AM function. Interventions to restore airway GSH homeostasis may be warranted in children with severe asthma.
To study the association between copper, magnesium and malondialdehyde levels in seminal plasma of oligozoospermic, azoospermic in relation to normozoospermic men.
The present study was conducted at the Chemistry and Biochemistry department, College of Medicine, Al-Nahrain University, Baghdad-Iraq during September 2007 to February 2008 after obtaining approval from the research and ethics committee and obtaining written consent, 78 infertile men (age range 33.01±4.20 years) were recruited at the institute of embryo research and infertility treatment, Al-Kadhimiya teaching hospital, Iraq and were categorized according to their seminal fluid parameters to oligozoospermia (n=43) and azoospermia (n=35). 41 fertile men (age range 30.29±2.30 years) were selected as controls. Seminal plasma copper and magnesium were measured by atomic absorption spectrophotometry. Malondialdehyde was measured calorimetrically using thiobarbituric acid assay which detects thiobarbituric acid reactive substances.
Seminal plasma copper level was decreased significantly (p=0.000) in the azoospermic group compared to the control group. Whereas, the level decreased non-significantly in the oligozoospermic group. Seminal plasma magnesium levels were decreased significantly (p=0.000) in all the infertility groups studied. On the other hand, malondialdehyde levels which is an end product of lipid peroxidation were significantly elevated (p=0.000) in all the infertility groups studied.
Copper and magnesium work in different ways in order to maintain normal environment for spermatozoa for normal fertilization to occur.
Defective sperm function is the most common cause of infertility. A prospective study was carried out to correlate the concentration of nitrite (the stable metabolite of nitric oxide) in seminal plasma with leukocytospermia, and sperm membrane integrity. Total Fifty-seven normozoospermic subjects with and without leukocytospermia visiting the Infertility clinic at KH and MRC, Karad, were included in the present study. Semen samples were checked for sperm concentration, total sperm count, sperm motility, seminal leukocyte concentration and sperm membrane integrity as Hypoosmotic Swelling Test. Similarly the concentration of nitrite in seminal plasma was measured by Griess reaction and total antioxidant power measured as ferric reducing ability of plasma. The concentration of nitrite in seminal plasma was found to be raised with significantly increased leukocyte concentration in semen. Also significantly lowered levels of total antioxidant power along with defective sperm function was observed. Our results suggest that supplementary treatment of antioxidants with antibiotic for leukocytospermic infertile male patients may improve the sperm membrane integrity.
Leukocytes and Total antioxidant power; Nitric oxide (as a nitrite); Sperm membrane integrity
The changes in the erythrocyte lipid peroxidation products (MDA), levels of glutathione (GSH), ascorbic acid and plasma vitamin E (non enzymatic antioxidant parameters) and activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase in erythrocytes and plasma glutathione - S - transferase (GST) activity were estimated in patients with rheumatoid arthritis. This work was undertaken to assess oxidative stress and anti oxidant status in patients with rheumatoid arthritis. It was observed that there was a significant increase in erythrocyte MDA levels, activities of SOD, GPX, plasma GST and a significant decrease in erythrocyte GSH, ascorbic acid, plasma vitamin E levels and catalse activity in patients with rheumatoid arthritis when compared to controls. The results of our study suggests higher oxygen free radical production, evidenced by increased MDA and decreased GSH, ascorbic acid, vitamin E and Catalase activity, support to the oxidative stress in rheumatoid arthritis. The increased activities of antioxidant enzymes may be a compensatory regulation in response to increased oxidative stress.
Malondialdehyde; Glutathione; Ascorbic acid; Vitamin E; Superoxide dismutase; Catalase; Glutathione peroxidase; Glutathione -S - transferase; Rheumatoid arthritis
This study evaluated the extent of oxidative stress by measuring malondialdehyde and ascorbic acid in the seminal plasma of human subjects with different fertility potential. Semen samples from 148 subjects were evaluated (48 normozoospermics, 34 oligoasthenoteratozoospermics, 34 asthenoteratozoospermics and 32 azoospermics). malondialdehyde level was found to be significantly higher in the abnormal groups (oligoasthenoterato and asthenoterato-zoospermics) than normozoospermics (P < 0.01). Negative correlation was also found between malondialdehyde level, sperm concentration, sperm motility and sperm morphology. Level of ascorbic acid was found to be significantly higher in normozoospermics than other abnormal groups (P < 0.01). It was found to be correlated positively with all seminogram parameters and negatively with malondialdehyde level. The study revealed that, excess lipid peroxidation reflected by high malondialdehyde level with reduced ascorbic acid in human seminal plasma is associated with poor semen quality where as ascorbic acid content has positive correlation with fertility potential.
Ascorbic acid; Infertility; Oxidative stress; Human Seminal Plasma
To investigate whether orbital fibroblasts from patients with Graves’ ophthalmopathy (GO) are more responsive to oxidative stress.
Lipid peroxidation, oxidative DNA damage, reactive oxygen species (ROS) contents and activities of antioxidant enzymes were measured in cultured orbital fibroblasts from GO patients and age-matched normal controls in response to 200 μM hydrogen peroxide (H2O2).
GO fibroblasts had increased basal levels of malondialdehyde (MDA), 8-hydroxy 2'-deoxyguanosine, superoxide anions, H2O2, and manganese-dependent superoxide dismutase (Mn-SOD) activity, as well as decreased glutathione peroxidase (GPx) activity and the ratio between reduced (GSH) and oxidized glutathione (GSSG) compared with the orbital fibroblasts from normal subjects. After treatment of the cells with 200 μM H2O2, the amplitude of increase in the intracellular levels of MDA (63% versus 26%), H2O2 (24% versus 13%) and Mn-SOD activity (48% versus 23%) was exaggerated in GO fibroblasts compared with normal controls, respectively. In addition, treatment of GO fibroblasts with 200 μM H2O2 led to a dramatic reduction of catalase activity (−59% versus −29%), GPx activity (−56% versus −13%), and GSH/GSSG ratio (−49% versus −21%), respectively.
Elevated ROS and redox imbalance in GO orbital fibroblasts were exacerbated by H2O2 as a result of exhaustion of GSH and compromise of antioxidant enzymes. Hypersensitivity to oxidative stress of GO orbital fibroblasts may play a role in the pathogenesis of GO.
Objectives: Reactive oxygen species (ROS) induced lipid peroxidation is associated with sperm function. Malondialdehyde (MDA) concentration and glutathione peroxidase (GPx) activity represent the lipid peroxidation and spermicidal antioxidant, respectively. We aimed to evaluate the relationship of MDA and GPx levels with sperm parameters.
Patients and methods: Specimens were divided into two groups: group 1. normospermia (n=20); group 2. oligoasthenospermia (n=31). Seminal MDA concentration was measured by thiobarbituric acid reaction method. Seminal GPx activity was measured by oxidation of reduced nicotinamide-adenine dinucleotide. Seminal MDA levels and GPx activities in both groups were compared.
Results: MDA concentrations in both groups were significantly different (1.52 ± 0.75 vs. 2.25 ± 0.88 nM, p = 0.0021). GPx activities in both groups were non-significantly different (0.48 ± 0.11 vs. 0.47 ± 0.12 U/ml). MDA levels were negatively correlated with the sperm motility (MDA = -0.014 x motility + 2.62, p =0.017) and concentration (MDA = -0.0045 x concentration + 2.23, p = 0.0166). GPx activities were positively but non-significantly correlated with the sperm concentration and sperm motility.
Conclusions: Seminal MDA concentrations are negatively correlated with sperm concentration and motility, which might provide a simple and useful tool in predicting sperm parameters. GPx activity is non-significantly correlated with the seminal quality. Roles of seminal MDA upon spermatogenesis merits further surveys.
glutathione peroxidase; malondialdehyde; oligoasthenozoospermia; semen; sperm
DNA damage may occur during sperm processing, thereby negatively influencing fertilizing ability of the sperm. The present study was designed to compare the effectiveness of gradient and swim-up, either alone or in combination, to eliminate sperm with DNA damage.
A total of 51 subjects visiting the University infertility clinic with normozoospermic parameters, oligozoospermia and teratozoospermia were included. Semen characteristics were analysed by standard criteria; Terminal deoxy nucelotidyl transferase mediated dUTP nick end labeling assay was employed for DNA damage assessment.
The percentage of TUNEL positive sperm after sperm processing was significantly lower in normozoospermic (P < 0.05), oligozoospermic (P < 0.001) and teratozoospermic samples (P < 0.01). No difference was observed in the incidence of TUNEL positive sperm between the various techniques, suggesting that they are comparable.
Sperm preparation has been found to result in enrichment of sperm with intact chromatin, which is likely to improve the chances of achieving a viable pregnancy.
Sperm DNA damage; Sperm selection; Semen preparation; Swim-up; Density gradient
Abnormal spermatozoa frequently display typical features of oxidative stress, i.e. excessive level of reactive oxygen species (ROS) and depleted antioxidant capacity. Moreover, it has been found that a high level of oxidatively damaged DNA is associated with abnormal spermatozoa and male infertility. Therefore, the aim of our study was the comparison of oxidative stress/DNA damage in semen and blood of fertile and infertile men. The broad range of parameters which describe oxidative stress and oxidatively damaged DNA and repair were analyzed in the blood plasma and seminal plasma of groups of fertile and infertile subjects. These parameters include: (i) 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) levels in urine; (ii) 8-oxodG level in DNA isolated from leukocytes and spermatozoa; (iii) antioxidant vitamins (A, C and E) and uric acid. Urinary excretion of 8-oxodG and 8-oxoGua and the level of oxidatively damaged DNA in leukocytes as well as the level of antioxidant vitamins were analyzed using HPLC and HPLC/GC/MS methods.
The results of our study demonstrate that 8-oxodG level significantly correlated with every parameter which describe sperm quality: sperm count, motility and morphology. Moreover, the data indicate a higher level of 8-oxodG in sperm DNA compared with DNA of surrogate tissue (leukocytes) in infertile men as well as in healthy control group. For the whole study population the median values of 8-oxodG/106 dG were respectively 7.85 and 5.87 (p = 0.000000002). Since 8-oxodG level in sperm DNA is inversely correlated with urinary excretion rate of 8-oxoGua, which is the product of OGG1 activity, we hypothesize that integrity of spermatozoa DNA may be highly dependent on OGG1 activity. No relationship between the whole body oxidative stress and that of sperm plasma was found, which suggests that the redox status of semen may be rather independent on this characteristic for other tissues.
This study investigated the effect of physical training and oxidative stress on the antioxidative activity and on plasma lipid profile. Forty eight rats were given either a physical training or no training for 4 weeks and were then subdivided into 3 groups: before-exercise (BE); during-exercise (DE); after-exercise (AE). The antioxidative activity was evaluated with the activities of catalase in plasma and superoxide dismutase (SOD), the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) and the level of malondialdehyde (MDA) in liver. The plasma concentrations of triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C)) were also compared. Compared to those of non-training group, catalase activities of training group were lower before exercise but higher during and after exercise. SOD activities were higher regardless of exercise. GSH/GSSG ratio was higher before exercise but was not significantly different during exercise and even lower after exercise. There were no differences between non-training group and training group in MDA levels regardless of exercise. Compared to those of non-training group, atherosclerotic index of training group was lower after exercise and there were no significant differences before and during exercise. There were no differences between non-training group and training group in HDL-C regardless of exercise. These results suggest that moderate physical training can activate antioxidant defenses and decrease the atherosclerotic index and this beneficial effect is evident under exercise-induced oxidative stress.
Physical training; exercise induced-oxidative stress; antioxidative enzyme activity; lipid profile
There is clinical evidence to show that sperm DNA damage could be a marker of sperm quality and extensive data exist on the relationship between DNA damage and male fertility status. Detecting such damage in sperm could provide new elements besides semen parameters in diagnosing male infertility. We aimed to assess sperm DNA fragmentation and oxidation and to study the association between these two markers, routine semen parameters and malondialdehyde formation.
Semen samples from 55 men attending the Histology-Embryology Laboratory of Sfax Faculty of Medicine, Tunisia, for semen investigations were analysed for sperm DNA fragmentation and oxidation using flow cytometry. The Sperm was also assessed spectrophotometrically for malondialdehyde formation.
Within the studied group, 21 patients were nonasthenozoospermic (sperm motility ≥ 50%) and 34 patients were considered asthenozoospermic (sperm motility < 50%). A positive correlation was found between sperm DNA fragmentation and oxidation (p = 0.01; r = 0.33). We also found a negative correlation between sperm DNA fragmentation and some sperm parameters: total motility (p = 0.001; r = -0.43), rapid progressive motility (type a motility) (p = 0.04; r = -0.27), slow progressive motility (type b motility) (p = 0.03; r = -0.28), and vitality (p < 0.001; r = -0.65). Sperm DNA fragmentation was positively correlated with coiled tail (p = 0.01; r = 0.34). The two parameters that were found to be correlated with oxidative DNA damage were leucocytes concentrations (p = 0.01; r = 0.38) and broken neck (p = 0.02; r = 0.29). Sperm MDA levels were negatively correlated with sperm concentration (p < 0.001; r = -0.57), total motility (p = 0.01; r = -0.35) and type a motility (p = 0.03; r = -0.32); but not correlated with DNA fragmentation and DNA oxidation.
Our results support the evidence that oxidative stress plays a key role in inducing DNA damage; but nuclear alterations and malondialdehyde don't seem to be synchronous.
BACKGROUND--There is mounting clinical evidence that ethanol toxicity to the pancreas is linked with glutathione depletion from oxidative stress but there is not experimental proof that this occurs. AIMS AND METHODS--The effect of acute ethanol ingestion (4 g/kg) on the pancreatic content of reduced (GSH) and oxidised (GSSG) glutathione, malondialdehyde (MDA), and carbonyl proteins were therefore studied in the rat. RESULTS--Ethanol caused a significant reduction in GSH (p < 0.02) and an increase in GSSG (p < 0.005), MDA (p < 0.05), and carbonyl proteins (p < 0.05) in the rat pancreas. The GSH/GSSG ratios were significantly decreased after ethanol, especially in rats pretreated with diethylmaleate (DEM), a GSH blocker. Administration of ethanol after DEM further increased the rate of lipid and protein oxidation. Pretreatment with cyanamide (an inhibitor of aldehyde dehydrogenase) but not with 4-methylpyrazole (an alcohol dehydrogenase inhibitor) caused higher production of GSSG and MDA. CONCLUSIONS--These findings indicate that acute ethanol reduces the pancreatic content of GSH, which seems to be protective against ethanol toxicity, since its depletion is accompanied by increased oxidative damage to cell structures. The further increase of lipid peroxidation and GSSG production in the presence of cyanamide suggests that acetaldehyde might be responsible for the oxidative changes that occur in pancreatic cells after ethanol administration.
Nitric oxide (NO) is synthesized from L-arginine by a family of enzymes known as nitric oxide synthases. Low concentrations of NO is essential in biology and physiology of spermatozoa, but high amounts of NO is toxic and has negative effects on sperm functions. Moreover, sperm membrane contains high concentrations of polyunsaturated fatty acids that are highly susceptible to oxidative damage that interferes with fertilization ability. Therefore, we investigated the correlation between levels of sperm malondialdehyde (MDA) and NO with sperm motility in male smokers.
Semen samples were collected from normozoospermic smoker (n=64) and nonsmoker (n=83) men. The content of sperm lipid peroxidation was determined by measuring malondialdehyde (MDA). The sperm NO were also measured using Griess reagent. Data was analyzed by SPSS, (version 15.0), using independent t-test and Pearson analysis.
The mean MDA and NO concentrations in the sperm of normozoospermic male smokers were significantly higher than the control group or normozoospermic nonsmokers, (p <0.001). A significant negative relationship was noted between sperm motility and sperm MDA levels (r=−0.32, p=0.01); and sperm motility and sperm NO concentration (for nitrite, r=−0.34, p=0.006 and for nitrate, r=−0.38, p=0.002).
It was concluded that the increase in MDA and NO production in sperm can influence sperm motility in normozoospermic smokers. Therefore, it seems that cigarette smoking may affect the fertility of male smokers via increasing the amount of sperm MDA/lipid peroxidation and NO concentrations.
Cigarette smoking; Human sperm; Lipid peroxidation; Nitric oxide; Smoker men
We investigated both the effect of levosimendan and the role of oxidant/antioxidant status and trace element levels in the pulmonary artery of rats. Fourteen male Wistar albino rats were randomly divided into two groups of seven animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.9 % NaCl was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their pulmonary arteries were harvested to determine changes in tissue oxidant/antioxidant status and trace element levels. The animals in both groups were killed 72 h after the levosimendan exposure treatment, and pulmonary arteries were harvested to determine levels of the lipid peroxidation product MDA and the antioxidant GSH as well as the decreased activity of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA levels increased in pulmonary artery tissues of rats after levosimendan administration. The GSH level decreased in the pulmonary artery of rats after levosimendan treatment. Co, Mn, Fe, Cd and Pb levels were significantly higher (P < 0.001) and Mg, Zn and Cu levels significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in the pulmonary artery of levosimendan-treated rats. It also caused a decrease or increase in the levels of many minerals in the pulmonary artery, which is an undesirable condition for normal pharmacological function.
Levosimendan; Oxidative stress; Free radical; Oxidant/antioxidant; Pulmonary artery
The aim of this study was to evaluate the plasma concentrations of malondialdehyde (MDA) and nitric oxide (NO) and the plasma activities of oxidant and antioxidant enzymes in patients with IBS.
A total of 36 patients with IBS were included in the study. Thirty-five healthy subjects were selected to form the control group. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO), adenosine deaminase (AD) activities, and malondialdehyde (MDA) and nitric oxide (NO) concentrations were studied in the serum samples of all patients and controls.
Plasma XO and AD activities, and MDA and NO concentrations were significantly higher in IBS patients than in controls. The SOD, CAT, and GSH-Px activities in the serum of patients with IBS were significantly lower than that of controls.
These results suggest that lipid peroxidation and alterations in the oxidant-antioxidant enzymatic system may play a role in the pathogenesis of IBS. Increased lipid peroxidation in IBS may be related to an increase in NO level and XO activity and a decrease in antioxidant enzymes activities. In addition, increased AD activity may have a role in immunological changes of IBS patients.
irritable bowel syndrome; malondialdehyde; nitric oxide; oxidant enzyme; antioxidant enzymes
Oxidative stress contributes to the cascade, leading to dopamine cell degeneration in Parkinson’s disease. However, oxidative stress is intimately linked to other components of the degenerative process, such as mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity and inflammation. It is therefore difficult to determine whether oxidative stress leads to or is a consequence of, these events. Oxidative stress was assessed by estimating lipid peroxidation product in the form of thiobarbituric acid reactive substances, nitric oxide in the form of nitrite & nitrate. Enzymatic antioxidants in the form of superoxide dismutase, glutathione peroxidase, catalase, ceruloplasmin and non enzymatic antioxidant vitamins e.g. vitamin E and C in either serum or plasma or erythrocyte in 40 patients of Parkinson’s disease in the age group 40–80 years. Trace elements e.g. copper, zinc and selenium were also estimated. Plasma thiobarbituric acid reactive substances and nitric oxide levels were Significantly high but superoxide dismutase, glutathione peroxidase, catalase, ceruloplasmin, vitamin-E, vitamin-C, copper, zinc and selenium levels were significantly low in Parkinson’s disease when compared with control subjects. Present study showed that elevated oxidative stress may be playing a role in dopaminergic neuronal loss in substentia nigra pars compacta and involved in pathogenesis of the Parkinson’s disease.
Oxidative stress; Antioxidants; Pathogenesis; Parkinson’s disease
There is growing evidence that damage to spermatozoa by reactive oxygen species (ROS) play a key role in male infertility. The aim of the present study was to assess seminal plasma levels of total antioxidant capacity (TAC), free 8-Isoprostane and activities of catalase and superoxide dismutase (SOD) in men with asthenozoospermia, asthenoteratozoospermia and oligoasthenoteratozoospermia compared with normozoospermic males.
The patients consisted of 46 men with seminal parameters abnormalities. The patients were grouped into asthenozoospermic (n = 15), asthenoteratozoospermic (n = 16) and oligoasthenoteratozoospermic (n = 15). The control group consisted of 16 healthy males with normozoospermia. Catalase activity was measured by Aebi spectrophotometeric method. Levels of TAC and SOD were measured by commercially available colorimetric assays. Level of free 8-Isoprostane was assessed by commercially available enzyme immunoassay (EIA) method. Differences between groups were assessed using Mann-Whitney U test and Kruskal-Wallis test. Coefficients of correlation were calculated using Spearman's correlation analysis. All hypothesis tests were two-tailed with statistical significance assessed at the p value < 0.05 level with 95% confidence intervals
Levels of catalase and TAC were significantly lower in patients than the control group. No significant changes were seen in SOD activities. Levels of free 8-Isoprostane were significantly higher in patients than the control group. Furthermore, asthenozoospermic, asthenoteratozoospermic and oligoasthenoteratozoospermic groups had significantly lower values of catalase activity and TAC when compared to normozoospermic males. Levels of free 8-Isoprostane were significantly higher in all patients subgroups than the control group. Levels of catalase and TAC were positively correlated with sperm motility and morphology. Free 8-Isoprostane levels showed an inverse correlation with sperm motility and morphology.
Decreasing seminal plasma antioxidants levels, especially catalase and TAC, could have significant role in etiology of impaired sperm function. Measurement of 8-Isoprostane may be used as a specific biomarker for assessing oxidative stress on sperm.
The thiol-containing tripeptide glutathione is an important cellular constituent of many eukaryotic and prokaryotic cells. In addition to its disulfide reductase activity, glutathione is known to protect cells from many forms of physiological stress. This report represents the first investigation into the role of glutathione in the Gram-positive pathogen Streptococcus pneumoniae. We demonstrate that pneumococci import extracellular glutathione using the ABC transporter substrate binding protein GshT. Mutation of gshT and the gene encoding glutathione reductase (gor) increases pneumococcal sensitivity to the superoxide generating compound paraquat, illustrating the importance of glutathione utilization in pneumococcal oxidative stress resistance. In addition, the gshT and gor mutant strains are hypersensitive to challenge with the divalent metal ions copper, cadmium, and zinc. The importance of glutathione utilization in pneumococcal colonization and invasion of the host is demonstrated by the attenuated phenotype of the gshT mutant strain in a mouse model of infection.
Male infertility is a serious problem all over the world. Nutritional deficiency of trace element Zinc (Zn) may play a role in male infertility as Zn plays an important role not only in normal testicular development, but also in spermatogenesis and sperm motility. Deficiency of Zn is associated with hypogonadism and insufficient development of secondary sex characteristics.
The present study was designed to analyze the level of seminal Zn among different groups of infertile patients and to correlate it with sperm concentration, active, sluggish and immotile fractions of seminal parameters, with an objective to establish the role of Zn in male infertility.
Setting and Design:
The present study was carried out in five- years period from 2004 to 2009. It was a descriptive analytical study with non probability sampling.
Materials and Methods:
Semen examination of the patients was carried out according to the standardized method of the World Health Organization. Semen Zn was estimated by color 5 Br. PAPS method.
All statistical analyses were performed by using SPSS (Version 14.0 for windows) software, by applying student's t-test.
The result showed that seminal Zn was 702.92±10.60, 598.48±12.95, 617.54±9.55, 542.29±22.75, 710.36±7.87, 712.06±7.96, 789.36±21.33, and 762.06±8.99 mg/dl in azoospermic, oligozoospermic, asthenozoospermic, oligoasthenozoospermic, teratozoospermic, normozoospermic, polyzoospermic, and proven fathers group, respectively.
Decreased concentration of seminal Zn do affect the sperm count, while increased level of seminal plasma Zn causes decreased sperm motility; so, it is suggested that administration of Zn should be very carefully monitored in such patients having low sperm count but normal sperm motility, as adequate seminal Zn is required for normal sperm function.
Asthenozoospsermia; azoospermia; male infertility; oligozoospermia; seminal zinc