Murat Kizilgun

Protective effect of lycopene against ochratoxin A induced renal oxidative stress and apoptosis in rats

This study was designed to investigate the possible protective effect of lycopene against the renal toxic effects of OTA. Male Sprague-Dawley rats (<200 g, n=6) were treated with OTA (0.5 mg/kg/day) and/or lycopene (5 mg/kg/day) by gavage for 14 days. Histopathological examinations were performed and apoptotic cell death in both cortex and medulla was evaluated by TUNEL assay. Besides, biochemical parameters and activities of renal antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD); concentrations of total glutathione (GSH), and malondialdehyde (MDA) levels were measured. OTA treatment was found to induce oxidative stress in rat kidney, as evidenced by marked decreases in CAT (35%) activity and GSH levels (44%) as well as increase in SOD activity (22%) vs control group. Furthermore, TUNEL analysis revealed a significant increase in the number of TUNEL-positive cells in cortex (49%) and medulla (75%) in OTA administrated group compared to control (p<0.05). Lycopene supplementation with OTA increased GPx1 activity and GSH levels, and decreased apoptotic cell death in both cortex and medulla vs. control. The results of this study showed that at least one of the mechanisms underlying the renal toxicity of OTA is oxidative stress and apoptosis is the major form of cell death caused by OTA. Besides, our data indicate that the natural antioxidant lycopene might be partially protective against OTA-induced nephrotoxicity and oxidative stress in rat.

The effects of di(2-ethylhexyl)phthalate on rat liver in relation to selenium status.

This study was performed to determine the hepatotoxicity of di(2‐ethylhexyl)phthalate (DEHP) in relation to selenium status. In 3‐week‐old Sprague‐Dawley rats, selenium deficiency was induced by a ≤0.05 selenium mg/kg. A selenium supplementation group was given 1 mg selenium/kg diet for 5 weeks. Di(2‐ethylhexyl)phthalate‐treated groups received 1000 mg/kg dose by gavage during the last 10 days of the experiment. Histopathology, peroxisome proliferation, catalase (CAT) immunoreactivity and activity and apoptosis were assessed. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR1)], superoxide dismutase (SOD), and glutathione S‐transferase (GST); aminotransferase, total glutathione (tGSH), and lipid peroxidation (LP) levels were measured. Di(2‐ethylhexyl)phthalate caused cellular disorganization while necrosis and inflammatory cell infiltration were observed in Se‐deficient DEHP group (DEHP/SeD). Catalase activity and immunoreactivity were increased in all DEHP‐treated groups. Glutathione peroxidase 1 and GPx4 activities decreased significantly in DEHP and DEHP/SeD groups, while GST activities decreased in all DEHP‐exposed groups. Thioredoxin reductase activity increased in DEHP and DEHP/SeS, while total SOD activities increased in all DEHP‐treated groups. Lipid peroxidation levels increased significantly in SeD (26%), DEHP (38%) and DEHP/SeD (71%) groups. Selenium supplementation partially ameliorated DEHP‐induced hepatotoxicity; while in DEHP/SeD group, drastic changes in hepatic histopathology and oxidative stress parameters were observed.

Di(2-ethylhexyl)phthalate-induced renal oxidative stress in rats and protective effect of selenium

This study was designed to examine the oxidative stress potential of di(2-ethylhexyl)phthalate (DEHP) on rat kidney and to evaluate possible protective effect of selenium (Se) status. Se deficiency (SeD) was produced in 3-week old Sprague−Dawley rats by feeding them ≤ 0.05 Se mg/kg diet for 5 weeks; Se supplementation group (SeS) was on 1 mg Se/kg diet. DEHP treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations of total glutathione (GSH), thiols and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP treatment was found to induce oxidative stress in rat kidney, as evidenced by significant decreases in GPx1 (~20%) and SOD (~30%) activities and GSH levels (~20%), along with marked decrease in thiol content (~40%) and increase in TBARS (~30%) levels. The effects of DEHP was more pronounced in SeD rats, whereas Se supplementation was protective by providing substantial elevations of GPx1 and GPx4 activities and GSH levels. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting renal tissue from the oxidant stressor activity of DEHP.

Ochratoxin A causes oxidative stress and cell death in rat liver

The effect of ochratoxin A (OTA) on oxidant/antioxidant status and on histopathological changes and apoptotic cell death in livers of male Sprague-Dawley rats has been investigated. OTA (0.5 mg/kg body weight/day) was administered by oral route for 14 days. Plasma biochemical parameters, activities of liver selenoenzymes (glutathione peroxidase-1, thioredoxin reductase) and antioxidant enzymes (catalase, superoxide dismutase, glutathione S-transferase), and levels of total glutathione and thiobarbituric acid reactive substance in hepatic tissue were measured. In addition, histopathological examinations were performed and apoptotic cell death of hepatocytes was evaluated by the TdT-mediated dUTP nick-end labelling (TUNEL) assay. OTA exposure was found to induce focal necrosis of hepatocytes and mononuclear cell infiltration. Besides, exposure to OTA caused an imbalance in oxidant and antioxidant parameters in the rat liver, as evidenced by significant decreases in glutathione S-transferase activity and glu...

Low zinc levels may contribute to gynecomastia in puberty

This study aimed to determine whether there were any differences in trace element levels between adolescent boys with gynecomastia and control boys and to determine the correlations between the levels of trace elements and body mass index (BMI) and sex hormones. The pubertal gynecomastia group comprised of 41 patients (mean age=13.2 ±0.9 years), who were admitted to Hacettepe University İhsan Doğramacı Childrens Hospital in Ankara. Control group comprised of 21 healthy male children. Analyses of trace element levels were performed atomic absorption spectrometry. The mean zinc level of control group was 101.33±16.87μg/dL and the mean zinc level of gynecomastia group was 81.36±17,43μg/dL (20% lower in gynecomastia patients, p=0.0001). However, the mean copper and manganese levels of gynecomastia patients were not statistically different than the control group. There were significant positive correlations between plasma zinc and total testosterone levels in gynecomastia group (r=0.592; p<0.05). There was a significant negative correlation between plasma zinc levels and BMI (r=-0.311; p<0.05). These results indicate that zinc deficiency might be one of the underlying factors of gynecomastia, the importance of which needs to be further elucidated.

Lycopene restores trace element levels in ochratoxin A-treated rats

Abstract This study was designed to investigate the in vivo effects of ochratoxin A (OTA) and/or lycopene on the levels of selenium, zinc, and copper in the liver, kidneys, and testes of male Sprague-Dawley rats. The rats were treated with OTA (0.5 mg kg-1 day-1) and/or lycopene (5 mg kg-1 day-1) by gavage for 7 or 14 days. Trace element levels were measured by atomic absorption spectrometry. OTA significantly lowered selenium (20 % in the liver, 17 % in the kidney, and 40 % in the testis), zinc (24 % in the liver, 23 % in the kidney, and 26 % in the testis), and copper levels (40 % in the liver and 10 % in the kidney). Lycopene alone did not affect the trace element levels in any of the organs. In combination with OTA, however, it significantly restored liver, kidney, and testis selenium and zinc levels compared to the group treated with OTA alone. Our results have confirmed that depletion of trace elements in different organs is one of the mechanisms of action of OTA. They also suggest that lycopene interferes with this depleting effect and restores trace element levels, the implications of which need to be further investigated.

Copper, zinc and iron levels in premature infants following red blood cell transfusion.

This study aimed to investigate effect of erythrocyte suspension (ES) transfusion on Cu, Zn, and Fe levels. It was conducted on 53 premature infants who were admitted to Hacettepe Hospital and received EST for first time. Blood samples were drawn before and 96h after ES transfusion to determine Cu, Zn, and Fe levels in plasma and/or erythrocytes. The mean plasma Cu levels were 99±3μg/dl and 113±3μg/dl; Zn levels were 105±2μg/dl and 115±23μg/dl; mean plasma Fe level was 58.1±19.4 and 75.2±25.4μg/dl and mean erythrocyte Fe level was 4182±2314μg/ml and 7009±5228μg/ml, before and after ES transfusion. The differences between before and after ES transfusion in Cu, Zn and Fe levels were significant. Correlation between plasma and erythrocyte Fe levels was significant both before and after ES transfusion. Though Fe overload is a major cause of morbidity/mortality after ES transfusion, alterations in trace elements should also be considered when transfusing blood to infants and children.