Ali Riza Kiziler

High Levels of Cadmium and Lead in Seminal Fluid and Blood of Smoking Men are Associated with High Oxidative Stress and Damage in Infertile Subjects

We measured the levels of malondialdehyde (MDA), protein carbonyls, glutathione S-transferase (GST) and reducte glutathione (GSH) in seminal plasma and spermatozoa from 95 subjects including 50 infertile patients to evaluate the association between oxidative stress and damage and the components of the anti-oxidant defenses in seminal plasma and spermatozoa of infertile subjects and concentrations of cadmium (Cd) and lead (Pb) in the blood and seminal plasma because of tobacco smoke exposure. The reactive oxygen species (ROS) in spermatozoa were also evaluated by luminol (5-amino-2,3-dihydro-1,4-phthalazinedione)-enhanced chemiluminescence assay. The sperm count, motility, and morphology in the smokers infertile group were found to be lower than those in the fertile male group and nonsmokers infertile group (p < 0.001). Concentrations of Cd, Pb, MDA, protein carbonyls, and ROS levels in the smokers infertile group were significantly higher than those in the fertile male and nonsmokers infertile male groups (p < 0.001). However, GSH levels and GST activities were decreased in the smokers infertile male group than those in the fertile male and nonsmokers infertile male groups (p < 0.001). The results indicate that smoking could affect semen quality and oxidative lipid and protein damage in human spermatozoa. From Pearson correlation analysis, positive correlations were demonstrated between the seminal plasma Cd and seminal plasma protein carbonyls and between seminal plasma Pb and spermatozoa ROS levels in smokers of the subfertile group, while there was a significant positive correlation between blood Cd and ROS levels in smokers of the fertile group. There was also a significant negative correlation of the Cd level of the blood and GSH levels of the sperm and seminal plasma. These findings suggest that cigarette smoking enhances the levels of Cd and Pb in seminal plasma and blood and the extent of oxidative damage associated with a decrease in components of the anti-oxidant defenses in the sperm of infertile males.

Impact of Cu and Fe concentrations on oxidative damage in male infertility

Oxidative stress in the reproductive system is thought to have an effect on the fertilizing ability of sperm. The purpose of this study was to assess the interaction of iron (Fe) and copper (Cu) ions in suspected subfertile and fertile male groups and to find out the relationships of the semen parameters (sperm count, motility, and abnormal morphology), glutathione, malondialdehyde, and reactive oxygen species with these variables. Semen and blood obtained from 60 subfertile men and from 40 fertile volunteers were examined. The sperm count and motility in the subfertile male group were found lower than those in fertile male group (p<0.001). Cu levels in serum and seminal plasma in the subfertile male group were significantly higher than those in the fertile male group (p<0.001 and p<0.05, respectively). There was also a significant increase in the Fe level of seminal plasma in the subfertile male group (p<0.001). However, there was no significant difference in the Fe level of serum in the subfertile male group. In conclusion, these findings suggest that Cu and Fe might be mediators of the effects of oxidative damage and play an essential role in spermatogenesis and male infertility; the determination of Fe and Cu levels in serum and seminal plasma during infertility investigation is recommended.

Lead and cadmium exposure in children living around a coal-mining area in Yatagan, Turkey

The study was designed to determine asymptomatic lead poisoning prevalence and cadmium exposure of preschool children living in a coal-mining area in Yatağan, Mugla, Turkey. The research was conducted between May and June 2002. The study included 236 children (53.4% female and 46.6% male) who were identified among the healthy children between the ages of 6 months and 6 years, using a systematic sampling method, from the records of the local medical centre of Yatağan. Assessments of the levels of blood lead and cadmium were performed by an atomic absorption spectrophotometer, in the Department of Biophysics, Cerrahpaşa Medical Faculty. The mean age of females and males were 49±18 and 43±19 months, respectively. The mean blood lead level was 33.8±15.6 μg/dL in females and 38.8±16.0 μg/dL in males. The mean blood lead level of the males was significantly higher than the females (P<0.05). Correlation analysis showed a statistically significant negative correlation between blood lead level and age in both sex groups (r=-0.367, P< 0.001). The blood lead level was found to be > 10 μg/dL in 95.7% and > 20 μg/dL in 87.6% of all children. The mean blood cadmium level of all children was 1.31±0.72 mg/dL. The blood cadmium level was found to be >0.5 μg/dL, which is considered to be toxic, in 85% of all children. The difference in blood cadmium levels between sexes was not significant. A statistically significant negative correlation was found between blood cadmium level and age of all children (r=-0.382, P<0.001). Although it is not possible to understand from this study what proportion of the biological lead and cadmium burden results from mining waste and what proportion comes from other sources, such as paint and gasoline residue deposited in soil and air, these results do indicate that asymptomatic lead poisoning and cadmium exposure are significant problems in children living in the Yatağan area. In conclusion, environmental lead measurements (house dust, soil, drinking water and air) must be performed, the results must be compared with the normal limits, and precautions must be taken if necessary in the Yatağan area. Future public health research efforts should focus on reducing the excessive levels of lead and cadmium in the environment.

The Role of Oxidative Stress and Antioxidant Defenses in Buerger Disease and Atherosclerotic Peripheral Arterial Occlusive Disease

The aim of this study was to determine the status and the role of oxidative stress and antioxidant defenses in patients with Buerger disease and atherosclerotic peripheral arterial occlusive disease (PAOD). Seventy-three subjects resembling each other in general characteristics were involved in the study: 21 with lower extremity PAOD (mean age 53.05 +/- 10.8 years, 17 men and four women), 22 with Buerger disease (mean age 38.59 +/- 6.4 years, 19 men and three women), and 30 healthy volunteers (mean age 38.59 +/- 6.4 years, 22 men and eight women). We measured the levels of plasma malondialdehyde (MDA), paraoxonase (PON1), protein carbonyls, arylesterase, nitric oxide (NO), serum oxidized low-density lipoprotein (ox-LDL) and MDA, glutathione (GSH), glutathione reductase (GSH-red), glutathione peroxidase (GSH-px), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes. Plasma protein carbonyls, serum ox-LDL, and plasma and erythrocyte MDA were significantly high in the Buerger disease group compared to the PAOD and control groups (p < 0.001). Plasma PON1 levels and GSH and GSH-px levels in erythrocytes in the Buerger disease group were significantly low compared to the PAOD and control groups (p < 0.001). GSH-red, SOD, and CAT levels in erythrocytes in the Buerger disease group were significantly lowcompared to the PAOD group (p < 0.01, p < 0.001, and p < 0.001, respectively). NO levels were significantly lower in the PAOD group compared to the control group (p < 0.05). The balance between oxidative stress and antioxidant capacity is more seriously impaired in Buerger disease than PAOD.

Relationships between levels of estradiol and testosterone in seminal plasma and GSTM1 polymorphism in infertile men.

Glutathione S-transferase M1 (GSTM1) enzyme serves as a steroid-binding protein by its ability to bind to testosterone and estradiol. The levels of total estradiol and testosterone were measured by using an electrochemiluminescence immunoassay in serum and seminal plasma from 103 subjects including 62 subfertile patients. GSTM1 polymorphism was examined using polymerase chain reaction. The estradiol and testosterone levels in seminal plasma were not different in control and subfertile subjects. No role for GSTM1 enzyme as a steroid-binding protein seemed likely as there was also no significant difference in seminal plasma estradiol and testosterone levels according to GSTM1 genoytpe. Significant positive correlations were found between seminal estradiol and serum estradiol in infertile males, and between seminal testosterone and serum testosterone in fertile males, independent of GSTM1 genotype. GSTM1 polymorphism is not a genetic risk factor of seminal estradiol and testosterone levels in infertile males although further studies are warranted.

Paraoxonase and arylesterase activities, lipid profile, and oxidative damage in experimental ischemic colitis model.

Objective. In the present study, since PON1 is known as an HDL-associated antioxidant enzyme that inhibits the oxidative modification of LDL and oxidative stress plays a role in the pathogenesis of mesenteric ischemia, we investigated the changes in PON1 activity and lipid profile in an experimental ischemic colitis model. Methods. Forty male Wistar albino rats were divided into two groups: the control group (N = 15) and the experimental group (N = 25). All animals were anesthetized with ether and ketamine anesthesia to undergo a midline laparotomy. Ischemic colitis was induced by marginal vessel ligation in the splenic flexura (devascularization process). A sham laparotomy was performed in the control group. All animals were sacrificed on the seventh postoperative day. Oxidative stress marker (malonyldialdehyde, MDA), lipid profile, and paraoxonase (PON-1) and arylesterase activities were determined. Histopathological evaluation was done under light microscopy, after sectioning and staining with hematoxyline and eosin. Statistical analysis was conducted using Students t-test and Mann-Whitney U test, and P < 0.05 was considered as statistically significant. Results. There was a significant decrease in both serum and tissue PON1 activity in ischemic colitis group (P < 0.01, for each). Similarly, arylesterase levels showed a parallel decrease in both tissue and serum of the experimental group (P < 0.01 and P < 0.001, retrospectively). MDA, an oxidative stress marker, was seen to increase in the experimental group (P < 0.01, tissue; P < 0.05, serum). In experimental group, there was a significant rise in serum total cholesterol and LDL levels (P < 0.001, for each). However, HDL level decreased significantly (P < 0.001). Triglycerides did not show any change between the groups (P > 0.05). Conclusions. PON1 and arylesterase play an important role in the pathophysiology of ischemic colitis.

Effect of Alpha-lipoic Acid Supplementation on Trace Element Levels in Serum and in Postmitotic Tissue in Aged Rats

Redistribution of redox-active divalent metal ions (e.g. copper, zinc, and iron) in postmitotic tissues of lipoic acid supplemented aging rats has been proposed to contribute to metal-catalyzed protein oxidation. DL-alpha lipoic acid (LA) (100 mg/kg body wt/day) was administered intraperitoneally to the Sprague-Dawley rats for 14 days. Serum copper levels lowered in the aged rats with LA supplementation compared to the rats without LA supplementation. On the other hand, serum zinc and iron levels increased in the aged rats with LA supplementation compared to the rats without LA supplementation. Copper levels of the postmitotic tissues were not changed in the aged rats with LA supplementation compared to the controls. The heart zinc levels detected in LA supplemented rats were significantly lower than controls. Similarly, the iron levels of the heart were found to be significantly lower in LA supplemented rats when compared to control rats. LA supplementation did not affect brain and muscle iron levels. The brain and muscle zinc levels remained the same in both group of rats. Based on the findings of our study, we have concluded that LA may exhibit prooxidant effect depending on the altered trace element homeostasis. Therefore, our results emphasize the importance of monitoring the dose of LA supplementation, duration of treatment and its potential harmful effects in the postmitotic tissues of aged rats.

Effect of Acute Alcohol Intake on Prostate Tissue and Serum PSA-Like Protein Levels in Rats

Objective: To investigate both the possible changes induced by acute alcohol intake on prostate tissue at the ultrastructural level and its effect on serum prostate-specific-antigen (PSA)-like protein levels in rats. Materials and Methods: 44 male Wistar rats were included in the study in four separate groups; 7 treatment and 4 control animals were selected for each group. The treatment group received 40% ethanol (6 g/kg) while the control group was injected with the same dose of intraperitoneal isotonic saline. The first group was sacrificed after 3 h, the second group after 24 h, the third group after 72 h and the fourth group on day 7. Samples were examined by light and Jeol-100 electron microscope. Total serum PSA-like protein levels were determined by a Tosoh immunoenzymometric analyzer AIA 600. Results: In groups 1–3, electron microscopy showed dilatations in the endoplasmic reticulum cisternae of prostatic acinar cells, disarrangements in apparent Golgi complex and apertures belonging to the basal labyrinth. It was also observed that there was a mass of debris cells inside the acinar lumen, and the secretory epithelium was detached from the basal membrane in some places. No pathology was found in group 4 by light and electron microscopy. In group 1, significant levels of increased serum total PSA-like protein were found compared to controls and other treatment groups (p = 0.006). Conclusions: The fundamental effect of acute alcohol intake on prostate tissue was observed in intermediate stages participating in the exocrine secretion process in the cellular organelles. At the same time, this influences the levels of serum PSA-like protein.

Serum Free Prostate-Specific Antigen and Zinc Levels in Experimental Acute Pancreatitis

Serum free prostate-specific antigen (fPSA) is the most useful tumor marker for prostatic cancer screening. However, recently, fPSA has also been detected in sera from patients with pancreatic diseases. In addition, it has been shown that zinc (Zn) concentration might change in both serum and tissues in pancreatic disease. In the present study, we measured serum concentrations of fPSA and Zn as possible markers and prognostic factors in an experimental acute-pancreatitis model. Twenty-five female Wistar albino rats were divided into two groups: the control group (n=10) and the experimental group (n=15). Acute pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. The animals were sacrificed 24 h later to detect the concentrations of serum fPSA and Zn. fPSA values were detected to be significantly higher in the experimental group p<0.001). There was also a significant decrease in the serum Zn level of the acute-pancreatitis group (p<0.001). In conclusion, these findings suggested that a combination of these parameters might represent a significant improvement on the diagnostic value of each of them separately and provide a powerful tool for differential diagnosis and prognosis in pancreatic diseases.

Impact of Testosterone, Zinc, Calcium and Magnesium Concentrations on Sperm Parameters in Subfertile Men

To investigate the impact of testosterone, zinc, calcium and magnesium concentrations in serum and seminal plasma on sperm parameters. There were significant decrease in sperm parameters, serum and seminal plasma zinc levels in subfertile males. It indicates zinc has a essential role in male infertility; the determination the level of zinc during infertility investigation is recommended.