Investigation of Zinc on hemorheological parameters in a rat model of diabetes.

Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6-115.2 - 172.8-230.4 s -1). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s-1. Erythrocyte rigidity index (Tk) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in Tk in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased Tk and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health.

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker on oxidative stress and metabolism of elements in kidney of STZ-induced diabetic rats.

In diabetes, increased oxidative stress and impaired trace element metabolism play an important role in the pathogenesis of diabetic nephropathy. The objective of this research was to examine the outcomes of blocking the renin-angiotensin system, using either the angiotensin-converting enzyme inhibitor (ACEI), perindopril, or the angiotensin II type 1 (AT1) receptor blocker, irbesartan, on oxidative stress and trace element levels such as Zn, Mg, Cu, and Fe in the kidneys of diabetic rats that had been induced with streptozotocin. Thirty-two Wistar albino male rats were equally divided into four groups. The first group was used as a control. The second group of rats developed diabetes after receiving a single intraperitoneal dose of STZ. The third and fourth groups of rats had STZ-induced diabetes and received daily dosages of irbesartan (15 mg/kg b.w/day) and perindopril (6 mg/kg b.w/day) treatment, respectively. Biochemical analysis of the kidneys showed a distinct increase in oxidative stress, indicated by heightened levels of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activities, as well as reduced glutathione (GSH) levels in the kidneys of diabetic rats. In the kidneys of diabetic rats, the mean levels of Fe and Cu were found to be significantly higher than those of the control group. Additionally, the mean levels of Zn and Mg were significantly lower in the diabetic rats compared to the control rats. Both perindopril and irbesartan decreased significantly MDA content and increased SOD activities and GSH levels in the kidneys of rats with diabetes. The Zn and Mg concentrations in the kidneys of diabetic rats treated with perindopril and irbesartan were markedly higher than in untreated STZ-diabetic rats, while the Cu and Fe concentrations were significantly lower. The urinary excretion of rats treated with perindopril and irbesartan showed a pronounced increase in Cu levels, along with a significant reduction in Zn and Mg levels. Although diabetic rats demonstrated degenerative morphological alterations in their kidneys, both therapies also improved diabetes-induced histopathological modifications in the kidneys. Finally, the present results suggest that manipulating the levels of Zn, Mg, Cu, and Fe - either through ACE inhibition or by blocking AT1 receptors - could be advantageous in reducing lipid peroxidation and increasing antioxidant concentration in the kidneys of diabetic rats.

Assessing the effect of selenium on cyclin D1 level and nuclear factor kappa b activity in NIH/3T3 fibroblast cells at 2100 MHz electromagnetic field exposure.

Although there are numerous studies on the health impacts of electromagnetic field (EMF) of mobile phone operation frequency 2100 MHz, the published works present contradicting results. Long-term exposure to mobile phone frequencies has unclear health hazards. Therefore, it is important to investigate the molecular mechanism of possible biological effects in mobile phone exposure and to determine the corresponding biological markers. Towards this end, this study was designed to assess the effect of 200 nM selenium (Se) on cell viability% [trypan blue], cell cycle biomarker [cyclin D1] and the transcription factor [nuclear factor kappa b (NF-κB)] in NIH/3T3 fibroblast cells when exposed to 2100 MHz mobile phone frequency. When 2100 MHz EMF was exposed to NIH/3T3 fibroblast cells, the cell viability% was reduced, whereas cyclin D1 level and NF-kB activity increased. Also we show that Se supplementation decreases the effects of 2100 MHz EMF on these parameters. Although future studies will be required to investigate the biological effects of EMF emitted by mobile phones, the results obtained here provide an insight into the molecular mechanisms and specifically underlying selenium's protective effect against 2100 MHz EMF exposure.

The Association Between Trace Elements and Osmolality in Plasma and Aqueous Humor Fluid in Diabetic Rabbits.

Trace element metabolism plays an important role in the formation of diabetes and complications of diabetes. Although trace elements changes in lenses in diabetic cataract and glaucoma formation have been investigated, there were few studies evaluating trace elements levels in plasma and aqueous humor fluid in diabetic and non-diabetic conditions. Therefore, we aimed to investigate zinc (Zn), copper (Cu), and chromium (Cr) levels in plasma and aqueous humor fluids of rabbits in the diabetic rabbit model. New Zealand male rabbits were divided into two groups as control (n = 8), and diabetes (n = 8) induced by alloxane. At the end of the experimental period, the osmolality in blood, plasma, and aqueous humor fluids from rabbits were measured by osmometer and Zn, Cu, and Cr levels in plasma and aqueous humor fluid were measured by inductively coupled plasma-optical emission spectrophotometer (ICP-OES). The osmolality in blood, plasma, and aqueous humor fluid of the diabetic group was significantly increased compared to the control group (respectively p < 0.01, p < 0.001, p < 0.001). It was analyzed that plasma Zn and Cu levels of diabetic rabbits increased significantly (respectively, p < 0.01; p < 0.001), whereas Cr level significantly decreased according to the control group (p < 0.01). It was observed that Cr and Zn levels in aqueous humor fluid in diabetes group decreased (respectively p < 0.001 and p < 0.01), and a significantly increased in Cu level (p < 0.001) compared to the control group. Related with these changes that may occur in the eye due to the measured parameters, we consider that comparative studies of these types of diabetic animal models would be useful in the evaluation of diabetes and its complications.

The potential protective roles of zinc, selenium and glutathione on hypoxia-induced TRPM2 channel activation in transfected HEK293 cells.

Hypoxia induces cell death through excessive production of reactive oxygen species (ROS) and calcium (Ca2+) influx in cells and TRPM2 cation channel is activated by oxidative stress. Zinc (Zn), selenium (Se), and glutathione (GSH) have antioxidant properties in several cells and hypoxia-induced TRPM2 channel activity, ROS and cell death may be inhibited by the Zn, Se, and GSH treatments. We investigated effects of Zn, Se, and GSH on lipid peroxidation (LPO), cell cytotoxicity and death through inhibition of TRPM2 channel activity in transfected HEK293 cells exposed to hypoxia defined as oxygen deficiency.We induced four groups as normoxia 30 and 60 min evaluated as control groups, hypoxia 30 and 60 min in the HEK293 cells. The cells were separately pre-incubated with extracellular Zn (100 µM), Se (150 nM) and GSH (5 mM). Cytotoxicity was evaluated by lactate dehydrogenase (LDH) release and the LDH and LPO levels were significantly higher in the hypoxia-30 and 60 min-exposed cells according to normoxia 30 and 60 min groups. Furthermore, we found that the LPO and LDH were decreased in the hypoxia-exposed cells after being treated with Zn, Se, and GSH according to the hypoxia groups. Compared to the normoxia groups, the current densities of TRPM2 channel were increased in the hypoxia-exposed cells by the hypoxia applications, while the same values were decreased in the treatment of Zn, Se, and GSH according to hypoxia group. In conclusion, hypoxia-induced TRPM2 channel activity, ROS and cell death were recovered by the Se, Zn and GSH treatments.

Protective Effects of Zinc on 2.45 GHz Electromagnetic Radiation-Induced Oxidative Stress and Apoptosis in HEK293 Cells.

Several epidemiological studies have shown that exposure to electromagnetic radiation (EMR) can be harmful to human health. The purpose of this study was to examine oxidative parameters and apoptosis induced by EMR in human kidney embryonic cells (HEK293) and to investigate whether zinc (Zn) has protective effect on EMR-induced apoptosis in HEK293 cells. For our experiment, HEK293 cells were divided into four main groups, control, EMR, 50 µM Zn + EMR, and 100 µM Zn + EMR. HEK293 cells of EMR groups were exposed to 2.45 GHz EMR for 1 h. In Zn groups, HEK293 cells were incubated with different concentrations of Zn for 48 h before EMR exposure. Oxidative stress parameters were determined by spectrophotometric method; bcl-2 and caspase-3 were assessed immunohistochemically and TUNEL method was performed for apoptotic activity. EMR group had higher malondialdehyde (MDA) level and lower superoxide dismutase (SOD) activity compared with control group. In Zn-applied groups, MDA was decreased and SOD activity was increased compared with EMR group. The number of the apoptotic cells and caspase-3 immunopositive cells at EMR group was increased significantly compared with the control group, whereas bcl-2 was decreased. Besides, Zn-treated groups showed a significant reduction in the number of apoptotic cells and caspase-3 from that of EMR group, whereas there was an increase in bcl-2 immunopositivity. Our findings show that EMR caused oxidative stress and apoptotic activation in HEK293 cells. Zn seems to have protective effects on the EMR by increasing SOD activity and bcl-2 immunopositivity, decreasing lipid peroxidation and caspas-3 immunopositivity.

Effects of Quercetin on Lipid and Protein Damage in the Liver of Streptozotocin-Induced Experimental Diabetic Rats.

Quercetin (QR) is part of a subclass of flavonoids called flavonols. We aimed to investigate the effect of QR on malondialdehyde (MDA), advanced oxidation protein products (AOPPs), and glutathione peroxidase (GSH-Px) activity in the liver of diabetic rats. We compared four groups of male adult Wistar albino rats: a control group, an untreated diabetic group, diabetic groups treated with QR, and QR group. Diabetes was induced by a single injection of streptozotocin (STZ) (50 mg/kg). Animals were kept in standard condition. On the 31st day of the study, the liver tissue was removed for biochemical parameters and histopathological evaluations. In an untreated diabetic group, liver MDA and AOPP levels were significantly higher than all groups. QR treatment significantly decreased the increased MDA, AOPP levels, and increased the decreased GSH-Px enzyme activity in liver tissues. The QR-treated rats in the diabetic group showed an improved histological appearance. Lesser vesicular vacuolization and fibrotic areas were observed in the QR-treated diabetic group than in the diabetic group. The STZ-induced liver injury is associated with oxidative stress, and coadministration of QR may reduce this damage effectively in a rat model. Our results are also supported by morphological improvement in liver tissue. Therefore, we think QR may be effective in treating hyperglycemia and oxidative damage in diabetes.

Selenium supplementation ameliorates electromagnetic field-induced oxidative stress in the HEK293 cells.

There is a widespread use of 2.4 GHz electromagnetic radiation emitting devices especially in communication and education. Recent studies show the adverse effects of electromagnetic fields (EMF) such as oxidative stress, cellular damage and apoptosis on tissues. Selenium (Se) has an antioxidant properties by inhibiting oxidative damage being within the structure of antioxidant enzymes like glutathione peroxidase (GSH-Px) and it has also regulatory function for cell cycle and apoptosis. The aim of this study was to investigate the effect of Se on 2.4 GHz frequency EMF exposed human embryonic kidney cells (HEK293) by means of alterations in apoptotic and oxidative stress parameters. Our study was planned as control, EMF, 100 nM Se + EMF, 200 nM Se + EMF groups. EMF groups were exposed to 2.4 GHz EMF for 1 h, element groups were incubated with two different doses of Se added cell culture medium for 48 h before EMF exposure. MDA levels were significantly higher whereas SOD and GSH-Px activities were significantly lower in EMF compared to control. 100 and 200 nM Se + EMF application decreased MDA levels, increased SOD and GSH-Px activities than EMF. Apoptosis and caspase-3 were statistically significantly higher but bcl-2 was lower in EMF than control. Apoptosis and caspase-3 were lower in 100 and 200 nM Se + EMF, although bcl-2 were higher than EMF. In conclusion, Se has protective effects against 2.4 GHz EMF-induced oxidative stress by reducing lipid peroxidation, regulating SOD and GSH-Px activity. Also, Se has inhibitory effect on 2.4 GHz EMF induced apoptosis by increasing the expression of anti-apoptotic protein bcl-2 and suppressing apoptosis regulatory protein caspase-3.

The Effects of Lithium Administration on Oxidant/Antioxidant Status in Rats: Biochemical and Histomorphological Evaluations.

Present study was planned to determine possible dose-dependent effects of lithium (Li) on oxidant-antioxidant status and histomorphological changes in liver and kidney tissues. For this purpose, twenty-four Wistar male rats were equally divided into three groups: the rats in group I served as controls, drinking tap water without lithium. Groups II and III received 0.1 and 0.2 % lithium carbonate (Li2CO3) through their drinking water, respectively, for 30 days. At the end of the experimental period, lithium concentrations, levels of malondialdehyde (MDA) and glutathione (GSH) and superoxide dismutase (SOD) activities were measured in considered tissues. Histomorphological study was also performed on liver and kidney tissues. Compared to controls, MDA was significantly higher but GSH level lower in groups II and III. SOD activity was higher in group III, but no difference was determined in group II in liver tissue. In kidney tissue, there was no difference determined in MDA and GSH levels between control and experimental groups but SOD activity in groups II and III was significantly higher. In histologic sections of both experimental liver and kidney tissues, specific degenerations were observed. The results of the present study show that treatment with lithium carbonate may result in liver and kidney tissue abnormalities and oxidative damage.

Wi-Fi (2.45 GHz)- and mobile phone (900 and 1800 MHz)-induced risks on oxidative stress and elements in kidney and testis of rats during pregnancy and the development of offspring.

The present study was designed to determine the effects of both Wi-Fi (2.45 GHz)- and mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) on oxidative stress and trace element levels in the kidney and testis of growing rats from pregnancy to 6 weeks of age. Thirty-two rats and their 96 newborn offspring were equally divided into four different groups, namely, control, 2.45 GHz, 900 MHz, and 1800 MHz groups. The 2.45 GHz, 900 MHz, and 1,800 MHz groups were exposed to EMR for 60 min/day during pregnancy and growth. During the fourth, fifth, and sixth weeks of the experiment, kidney and testis samples were taken from decapitated rats. Results from the fourth week showed that the level of lipid peroxidation in the kidney and testis and the copper, zinc, reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and total antioxidant status (TAS) values in the kidney decreased in the EMR groups, while iron concentrations in the kidney as well as vitamin A and vitamin E concentrations in the testis increased in the EMR groups. Results for fifth-week samples showed that iron, vitamin A, and ß-carotene concentrations in the kidney increased in the EMR groups, while the GSH and TAS levels decreased. The sixth week results showed that iron concentrations in the kidney and the extent of lipid peroxidation in the kidney and testis increased in the EMR groups, while copper, TAS, and GSH concentrations decreased. There were no statistically significant differences in kidney chromium, magnesium, and manganese concentrations among the four groups. In conclusion, Wi-Fi- and mobile phone-induced EMR caused oxidative damage by increasing the extent of lipid peroxidation and the iron level, while decreasing total antioxidant status, copper, and GSH values. Wi-Fi- and mobile phone-induced EMR may cause precocious puberty and oxidative kidney and testis injury in growing rats.

Basic fibroblast growth factor attenuates bisphosphonate-induced oxidative injury but decreases zinc and copper levels in oral epithelium of rat.

Recent studies have reported oxidative damage due to bisphosphonate (BP) in various cancer tissues and neurons, although basic fibroblast growth factor (bFGF) induced antioxidant effects in the cells. The bFGF may modulate the BP-induced oxidative stress in oral epithelium of rats. This study was undertaken to explore possible beneficial antioxidant effects of bFGF on oxidative stress induced by BP in oral epithelium of rats. Twenty-eight rats were equally divided into four groups. The first group was used as control. The second, third and fourth groups intraperitoneally received BP (zoledronic acid), bFGF and BP + bFGF. At the end of 10 weeks, the rats were sacrificed, and oral epithelium samples were taken for analyses. In BP group, the lipid peroxidation levels were increased in the oral epithelium, while the activities of glutathione peroxidase (GSH-Px) and the concentrations of total antioxidant status (TAS) were decreased. In rats treated with bFGF, lipid peroxidation levels decreased, and the activities of GSH-Px and concentrations of TAS improved in the oral epithelium. However, zinc and copper levels were decreased in the oral epithelium by BP and bFGF treatments. Concentrations of vitamin E and reduced glutathione in the samples did not change in the groups. In conclusion, treatment with bFGF modulated the antioxidant redox system and reduced the oral epithelium oxidative stress induced by BP. However, zinc and copper levels were decreased by BP and bFGF treatments.

Lithium-induced hypothyroidism: oxidative stress and osmotic fragility status in rats.

The present study was conducted to explore the possible effects of different doses of lithium carbonate on thyroid functions, erythrocyte oxidant-antioxidant status, and osmotic fragility. Twenty-four Wistar-type male rats were equally divided into three groups: groups I and II received 0.1 and0.2 % lithium carbonate in their drinking water, respectively, for 30 days. The rats in group III served as controls, drinking tap water without added lithium. At the end of the experimental period, the erythrocyte osmotic fragility and the levels of triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were measured in blood samples. Compared to controls, there was a statistically significant increase of TSH but decreases of the T3 and T4 levels in group II. Both experimental groups showed a statistically significant increase of the maximum osmotic fragility limit. The minimum osmotic fragility values of the animals in group II were statistically higher than those of controls. The standard hemolytic increment curve of both experimental groups was shifted to the right when compared to the curve obtained from the controls. Also, relative to controls, the activities of MDA and SOD were significantly higher and the GSH level lower in group II, but not so in group I. The results of the present study show that treatment with lithium carbonate may result in thyroid function abnormalities, increased oxidative damage, and possible compromise of the erythrocyte membrane integrity resulting from increased osmotic fragility.

Association of blood lead levels with demographic, reproductive and employment related factors in Turkish women.

OBJECTIVE: The aim of this study is to compare the blood lead levels in employed and unemployed women and associate the difference with sociodemographic and reproductive factors. PARTICIPANTS: Out of a 100 women attending the routine check-up unit of Family Medicine Department for screening of osteoporosis and blood lead levels, 63 post-menopausal participants; 36 unemployed and 27 employed, were included in the study. METHODS: Patients completed a questionnaire regarding their sociodemographics. Their blood chemistry and blood lead levels were determined and bone mineral densities were measured by Dual Energy X-Ray Absorptiometry. In the statistical analysis, Mann-Whitney U test was used to compare means and χ ^{2} was used to compare ratios. Backward logistic regression was used for multivariate analysis. RESULTS: There was no significant difference between the age (57.17 ± 7.46; unemployed, 54.19 ± 5.36; employed). The mean blood lead levels were 25.92 ± 9.31 µ g/dl in the unemployed group and 33.98 ± 13.50 µg/dl in the employed group (p=0.011) adjusted for age. Smoking rate was significantly higher in employed women (p=0.033) whereas the number of births (p=0.032) and duration of breastfeeding (p=0.008) were significantly lower. Although both groups were osteoporotic and post-menopausal, there was no association between osteoporosis and employment while unemployed women had an earlier menopause (p=0.037). CONCLUSIONS: Lead levels are above the accepted threshhold (20 µg/dl) in both groups. Strict environmental and social improvement efforts in both groups are recommended.

Zinc supplementation attenuates metallothionein and oxidative stress changes in kidney of streptozotocin-induced diabetic rats.

Zinc is an element that under physiological conditions preferentially binds to and is a potent inducer of metallothionein under physiological conditions. The present study was conducted to explore whether zinc supplementation morphologically and biochemically protects against diabetic nephropathy through modulation of kidney metallothionein induction and oxidative stress in streptozotocin-induced diabetic rats. Thirty-two Wistar albino male rats were equally divided into four groups. The first group was used as untreated controls and the second group was supplemented with 30 mg/kg/day zinc as zinc sulfate. The third group was treated with streptozotocin to induce diabetes and the fourth group was treated with streptozotocin and supplemented with zinc as described for group 2. The blood glucose and micro-albuminuria levels, body and kidney weights were measured during the 42-day experimental period. At the end of the experiment, the kidneys were removed from all animals from the four groups. Diabetes resulted in degenerative kidney morphological changes. The metallothionein immunoreactivity level was lower and the kidney lipid peroxidation levels were higher in the diabetes group than in the controls. The metallothionein immunoreactivity levels were higher in the tubules of the zinc-supplemented diabetic rats as compared to the non-supplemented diabetic group. The zinc and metallothionein concentrations in kidney tissue were higher in the supplemented diabetic group compared to the non-supplemented diabetes group. The activity of glutathione peroxidase did not change in any of the four groups. In conclusion, the present study shows that zinc has a protective effect against diabetic damage of kidney tissue through stimulation of metallothionein synthesis and regulation of the oxidative stress.

N-acetylcysteine attenuates copper overload-induced oxidative injury in brain of rat.

Copper is an integral part of many important enzymes involved in a number of vital biological processes. Even though it is essential to life, at elevated tissue concentrations, copper can become toxic to cells. Recent studies have reported oxidative damage due to copper in various tissues. Considering the vulnerability of the brain to oxidative stress, this study was undertaken to explore possible beneficial antioxidant effects of N-acetylcysteine on oxidative stress induced by copper overload in brain tissue of rats. Thirty-two Wistar rats were equally divided into four groups. The first group was used as control. The second, third, and fourth groups were given 1 g/L copper in their drinking water for 1 month. At the end of this period, the group 2 rats were sacrificed. During the next 2 weeks, the rats in group 3 were injected intraperitoneally with physiological saline and those in group 4 with 20 mg/kg intraperitoneal injections of N-acetylcysteine. In group 2 the lipid peroxidation and nitric oxide levels were increased in the brain cortex while the activities of superoxide dismutase and catalase and the concentration of glutathione were decreased. In rats treated with N-acetylcysteine, lipid peroxidation decreased and the activities of antioxidant enzyme improved in the brain cortex. In conclusion, treatment with N-acetylcysteine modulated the antioxidant redox system and reduced brain oxidative stress induced by copper.

Evaluation of trace elements and oxidative stress levels in the liver and kidney of streptozotocin-induced experimental diabetic rat model.

In this study, we aimed to investigate the relationship among trace elements (Cu, Fe, Zn and Mg) on oxidative and anti-oxidative substances in liver and kidneys tissues in streptozotocin (STZ) diabetic rat model. The mean levels of Fe and Cu were found significantly higher in the liver and kidneys of the diabetic rats, in comparison to the control rats. On the other hand, the mean levels of Zn and Mg in the liver and kidneys of the diabetic rats were significantly lower than in the control rats. The liver and kidneys malonaldehyde (MDA) levels of the experimental group were found to be higher than in the control group (p < 0.001; p < 0.01, respectively) after 4 weeks of the experimental period. Superoxide dismutase (SOD) activities and glutathione (GSH) levels in the liver tissue of STZ-induced diabetic rats were found to be lower in the experimental group than in the control group (p < 0.01). SOD activity and GSH concentration in kidneys of the diabetic rats were significantly diminished with respect to the control group (p < 0.01). In conclusion, the present results indicate that the increase of Fe and Cu together with decreas of Zn and Mg concentration in liver and kidney of STZ-induced diabetic rats may be involved in disturbances of oxidative balance in both the tissues. Therefore, these findings may contribute to explain the role of impaired ion metabolism of some elements in the progression of diabetic oxidative complications.

Copper intoxication; antioxidant defenses and oxidative damage in rat brain.

Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Even though Cu is essential to life, it can become toxic to cells, at elevated tissue concentrations. Oxidative damage due to Cu has been reported in recent studies in various tissues. In this study, we aimed to determine the effect of excess Cu on oxidative and anti-oxidative substances in brain tissue in a rat model. Sixteen male Wistar albino rats were divided into two groups: the control group, which was given normal tap water, and the experimental group, which received water containing Cu in a dose of 1 g/l. All rats were sacrificed at the end of 4 wk, under ether anesthesia. Cu concentration in the liver and in plasma alanine aminotransferase (ALT) and aspartate transaminase (AST) activities were determined. There were multiparameter changes with significant ALT and AST activity elevation and increased liver Cu concentration. In brain tissue, Cu concentration, superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels and glutathione (GSH) concentrations were determined. Brain Cu concentration was significantly higher in rats receiving excess Cu, compared with control rats (p < 0.05). Our results showed that SOD activities and GSH levels in brain tissue of the Cu-intoxicated animals were significantly lower than in the control group (p < 0.01 and p < 0,001, respectively). The brain MDA levels were found to be significantly higher in the experimental group than in the control group (p < 0.001). The present results indicate that excessive Cu accumulation in the brain depressed SOD activities and GSH levels and resulted in high MDA levels in brain homogenate due to the lipid peroxidation induced by the Cu overload.

Iron preloading aggravates nutritional steatohepatitis in rats by increasing apoptotic cell death.

BACKGROUND/AIMS: High serum ferritin and liver iron concentrations were found in some patients with NASH, suggesting a role for iron as a co-factor that aggravates liver injury. The aim of this study is to investigate the effects of parenteral iron in a rat model of NASH induced by a methionine choline deficient diet (MCDD). METHODS: Wistar rats were divided into 1 - Control, 2 - Iron (Fe), 3 - MCDD, 4 - MCDD&Fe groups. Iron dextran 100mg/kg was administered intra-muscularly in groups 2 and 4. All rats were fed MCDD, Groups 1 and 2 were supplied with choline and methionine. Blood and tissue samples were obtained after 4weeks. RESULTS: The iron injection alone did not affect the liver whereas MCDD led to steatohepatitis. Iron worsened steatosis without any obvious effect on accompanying inflammation. It aggravated tissue injury by increasing apoptosis. Liver fibrosis was observed only in 3 out of 10 rats in the MCDD&Fe group. CONCLUSIONS: Observation of liver fibrosis only in the MCDD&Fe group suggests that iron induced increase in apoptosis contributes to the development of fibrosis at an earlier time than expected.

Apoptotic rate and metallothionein levels in the tissues of cadmium- and copper-exposed rats.

It is well known that cadmium (Cd) has toxic and carcinogenic effects in rodents and humans, but the effects of Cd on apoptosis are still not clear. Although some studies have shown that Cd has apoptotic potential, other studies have shown that Cd can be antiapoptotic. Parameters such as sensitivity of the exposed organism or cells and the exposure conditions should be important in delineating the effect of Cd on apoptosis. In the present study, we aimed to determine the apoptotic index (AI) of Sprague-Dawley rat tissues that are loaded at a lower Cd concentration than the critical concentration (50 microg/g) for its toxic effects. Metallothionein (MT) levels of tissues were also determined and the experiments repeated with copper (Cu)-exposed rats. We detected decreases in the apoptotic index in liver and lung tissues of Cd-exposed groups accompanied with an increase in MT levels. Also, decreases of AI were detected in the liver tissues of Cu-exposed groups. These findings indicate that Cd can suppress apoptosis in vivo. The possible role of MT expression on the suppression of apoptosis and the importance of free-Cd ion concentration on switching antiapoptotic effects to proapoptotic effects are also discussed.

Changes in hemorheological parameters due to lead exposure in female rats.

Lead is an ubiquitous metal in the environment that induces a broad range of physiological, biochemical and behavioral dysfunctions. The purpose of this study was to investigate its effects on blood parameters and blood viscosity. Female rats (14 Wistar-Albino type) were divided into a control and a lead exposed group. Both groups were fed with the same standard food, but lead acetate was added to the drinking water of the experimental group for 5 weeks. At the end of the experimental period, blood samples were drawn from the abdominal aorta of the anaesthetized animals. Hematocrit (Hct %), hemoglobin (Hb), and the number of erythrocytes were determined, blood viscosity was measured with a rotational viscometer, and the lead concentration in blood was analyzed by means of flame atomic absorption spectrometry. The erythrocyte count, Hb and Hct % of the lead exposed group were found to be significantly lower than in the control group (p<0.01). The blood viscosity level was significantly higher compared to the control group (p<0.01). It can be concluded that increased lead concentrations in blood impair certain hemorheological mechanisms and increase blood viscosity.