Influence of chronic cadmium exposure on the tissue distribution of copper and zinc and oxidative stress parameters in rats.

The aim of this study was to investigate the effect of oral cadmium (Cd) intoxication on the antioxidant response and its relationship with essential bioelements like copper (Cu) and zinc (Zn). The experimental group was chronically exposed to Cd daily for 8 weeks via consumption of water containing 15 ppm cadmium chloride. Cu, Zn, and Cd concentrations and oxidative stress parameters were analyzed in liver, kidney, and heart tissues. Exposure to Cd led to a significant decrease in the activities of superoxide dismutase in all considered samples while a significant increase in the activity of glutathione peroxidase except for the kidney. We found a significant increase in malondialdehyde concentration in the tissues except for heart. Also oral administration of Cd caused a significant reduction of Zn and Cu in the tissues. Our results allow us to hypothesize that higher Cd concentration in the tissues causes oxidative stress by increasing malondialdehyde as a means of altering antioxidant defense system and deterioration of bioelements in rat liver, kidney, and heart. In addition, further studies are needed to explain the effect of long-term, low-dose exposure to Cd on distribution of bioelements and its relationship with oxidative stress.

Association between gene polymorphism of manganese superoxide dismutase and prostate cancer risk.

Manganese superoxide dismutase (MnSOD) is the most effective antioxidant enzyme in mitochondria and protects cells from reactive oxygen species-induced oxidative damage. The aim of this study was to investigate the association between MnSOD Ala-9 Val gene polymorphism and prostate cancer (PCa) risk in Turkish men with prostate cancer. 33 patients with PCa and 81 control individuals were included in the study. We observed an association between MnSOD Ala/Ala frequency and a higher PCa risk. In addition, we found that the increased risk of early-onset PCa (under age of 65) in the men homozygous for Ala allele was higher than the men homozygous for Val allele. However, we determined that MnSOD Ala-9 Val genotype was not associated with the aggressiveness of the disease. The results of our study suggest that MnSOD Ala/Ala genotype may influence on early-onset of PCa patients, but no effect on subsequent development of the disease in Turkish men. However, our study has a limitation that is small numbers of individuals for cases and controls. Therefore, the presented study limited our statistical power to fully investigate the gene polymorphism on cancer risk.

Evaluation of genotoxic and oxidative effects in workers exposed to jet propulsion fuel.

PURPOSE: Jet fuel is a common occupational exposure risk among military and civilian populations. The purpose of this study was to evaluate genotoxic and oxidative effects in workers occupational exposure to jet propulsion fuel (JP-8). METHODS: In this study, sister-chromatid exchange (SCE), high frequency of SCE cells (HFCs), and micronuclei (MN) were determined for 43 workers exposed to JP-8 and 38 control subjects. We measured the antioxidant enzyme activities including that of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT). The levels of thiobarbituric acid-reactive substances (TBARS) were also studied. Urinary 1- and 2-naphthol excretion was used as a biomarker of occupational exposure to JP-8. RESULTS: The results obtained from cytogenetic analysis show a statistically significant increase in frequency of SCE in the exposed workers when compared to controls (P < 0.05). Interestingly, the mean value of the frequency (%o) of MN and HFCs for workers and controls did not show any statistical differences (P > 0.05). Oxidative stress parameters were not statistically different between exposed and control groups except for TBARS levels. CONCLUSION: Urinary 1-and 2-naphthol levels of exposed workers were found to be significantly higher than those of control subjects. Occupational exposure to JP-8 resulted in no significant genotoxic and oxidative effects, while smoking is the principal confounding factor for the some parameters. To understand the genotoxic and oxidative effects of JP-8 exposure, further studies should be planned to find out whether human populations may be at increased risk for cancer because of the exposures related to occupation and lifestyle.

Cytogenetic analysis of peripheral blood lymphocytes of hospital staff occupationally exposed to low doses of ionizing radiation.

Ionizing radiation is known to induce mutations and cell transformations, predominantly by causing single-strand and double-strand DNA breakage, thereby leading to chromosome instability and carcinogenesis. The aim of this study was to evaluate genotoxic effects in hospital staff exposed to low-dose ionizing radiation in comparison with a selected control group, by using the cytokinesis-blocked micronucleus (CBMN) and sister chromatid exchange (SCE) tests in peripheral blood lymphocytes. The study included 40 exposed radiology staff and 30 control subjects. The frequency of micronuclei (MN) was significantly increased in radiation-exposed groups compared with control persons (p < 0.05). The frequency of SCE did not show any significant difference in the exposed individuals in comparison to the controls. Our results showed that low-level chronic occupational exposure to ionizing radiation causes an increase of MN frequency in chromosomes, even though the absorbed doses were below the permissible limits. Our studies indicate that the CBMN assay is considered to be sensitive test in contrast to SCE analysis to evaluate chromosomal damage induced by ionizing radiation.

[Investigation of oxidative stress and antioxidant defense in patients with hepatitis B virus infection and the effect of interferon-alpha plus lamivudine combination therapy on oxidative stress]. / Hepatit B virus enfeksiyonlu hastalarda oksidatif stres ve antioksidan kapasitenin arastirilmasi ve interferon-alpha-lamivudin kombinasyon tedavisinin oksidatif stres üzerine etkisi.

The aim of our study is to determine the role of oxidative stress on hepatic damage in patients with acute and chronic hepatitis B virus (HBV) infection and the efficacy of antioxidant-enzyme system against oxidative stress. Furthermore, the effect of interferon-alpha (IFN-alpha) plus lamivudine therapy on oxidative stress was also investigated. Nineteen patients with acute hepatitis B virus (AHBV) infection, 17 patients with chronic hepatitis B virus (CHBV) infection, 24 inactive HBsAg carriers and 21 healthy controls were included in the study. In control and patient groups, serum alanine-aminotransferase (ALT) and aspartate aminotransferase (AST) levels, erythrocyte malondialdehyde (MDA) levels, erythrocyte superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) activities were measured. In CHBV group, after IFN-alpha plus lamivudine therapy for 6 months, these parameters were measured again. In all patient groups erythrocyte MDA levels were detected higher than control group (p < 0.05). Activity of CuZn-SOD was found to be the highest in AHBV (p < 0.05), and the lowest before the treatment in CHBV group (p < 0.05) compared with other groups. Activity of GSH-Px was found to be the highest in AHBV compared with inactive HBsAg carriers (p < 0.05) and CHBV group before treatment (p < 0.05). Activity of GSH-Px was found to be the lowest in CHBV group before treatment compared with other groups (p < 0.05). In CHBV group there was a significant decrease of MDA levels after treatment (p < 0.05) while there was a significant increase in activity of CuZn-SOD and GSH-Px compared with pretreatment levels (p < 0.05). A significant positive correlation was determined between MDA values and serum ALT levels, before and after the treatment (p < 0.05). Detection of the increase of MDA levels which is a product of lipid peroxidation in all patient groups, indicates that the oxidative stress is increased in HBV infection. Correlation between the levels of erythrocyte MDA levels and serum ALT levels supports the hypothesis concerning the role of oxidative stress in pathogenesis of HBV infection. Insufficiency of antioxidant capacity in CHBV and inactive HBsAg carrier groups may lead to progression of disease and results in fibrosis. Treatment with IFN-alpha plus lamivudine causes a decrease in products of lipid peroxidation and shows antioxidant activity via increasing the antioxidant enzymes. These data suggest that the addition of antioxidant agents to IFN-alpha and lamivudin combination therapy may be useful in CHBV treatment. Further in-vitro and in-vivo studies are required to enlighten the role of antioxidants on HBV disease progression and treatment.

Manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with risk of early-onset prostate cancer.

Prostate cancer continues to be the most frequently diagnosed neoplasm, and the second leading cause of cancer-related mortality in men. Oxidative stress may enhance prostatic carcinogenesis. Manganese superoxide dismutase (MnSOD) is the only known superoxide scavenger in mitochondria. It plays a key role in antioxidant defense as mitochondria are important for oxidative metabolism coupled to the electron transport chain and oxidative phosphorylation and hence, ROS production. A T-->C single nucleotide substitution, resulting in a Val-->Ala change at position 9 (Ala-9Val), which alters the secondary structure of the protein, has been noted to affect transport of MnSOD into the mitochondria. We have determined the MnSOD genotype in 85 prostate cancer cases and 151 control subjects. Ala-9Val polymorphism was determined using real time polymerase chain reaction (PCR) amplification with fluorescently labeled primers. No significant difference was found in prostate cancer susceptibility in the subjects with Ala/Ala and Val/Ala genotype compared with Val/Val genotype (Odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.69-2.42; p = 0.416). We did not observe an association of the MnSOD genotype or allele frequency between subgroups of cases divided by disease status (aggressive vs. non-aggressive prostate cancer). However, in the analyses stratified by the age at diagnosis we have observed that men homozygous for Ala had a 5.2-fold increased risk of early-onset prostate cancer (under age of 65) compared to men homozygous for Val allele (p = 0.05). These data suggest that Ala/Ala MnSOD genotype in the Macedonian population could have an influence on early onset of prostate cancer, but no impact on the subsequent development of the disease.

Do N-acetylcystein, beta-glucan, and coenzyme Q10 mollify myocardial ischemia-reperfusion injury?

BACKGROUND: N-acetylcysteine, beta-glucan, and coenzyme Q10 have been shown to have antioxidant and anti-inflammatory effects on reperfusion injury. The aim of our study was to determine and evaluate the effects of these agents on myocardial ischemia-reperfusion injury. METHODS: Forty-four New Zealand white rabbits, all female, weighing 2.4 to 4.1 kg (mean, 3.6 kg) were used in the study. Four study groups of 11 animals were arranged by randomization. The groups were the control group (group C), a group premedicated with coenzyme Q10 (group Q), a group premedicated with beta-glucan (group betaT), and a group premedicated with N-acetylcysteine (group N). After exploration of the heart, a basal myocardial biopsy was taken from the anteroapical left ventricle, and the first blood sampling was done before ischemia. For the ischemia-reperfusion experiments, the major left anterior descending artery was occluded after baseline measurements. After a 45-minute transient ischemic period, the heart was perfused for 120 minutes. After perfusion, the second myocardial biopsy was taken from the anteroapical left ventricle, and the second blood sampling was done. Blood and tissue analysis were performed and evaluated statistically. RESULTS: Baseline and reperfusion levels of glutathione peroxidase, superoxide dismutase, malonyldialdehyde, and nitric oxide changed significantly. While malonyldialdehyde levels increased in group C, they decreased in the other study groups (P =.001). The increases in glutathione peroxidase and superoxide dismutase levels were significant in all groups except group C (P =.0001 and P <.05, respectively). Levels of nitric oxide were found to be decreased in group C, whereas they increased in the other groups (P =.001). CONCLUSION: Antioxidant medication may help in lowering the risk of myocardial ischemia-reperfusion injury. All the medications in our study are shown to have effective roles in preventing ischemia-reperfusion injury to some extent through their antioxidant properties.

Oxidative stress and antioxidant status in non-metastatic prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: We undertook the present study to investigate the possible alteration of oxidant/antioxidant status in the circulation of patients with prostate cancer and benign prostatic hyperplasia. DESIGN AND METHODS: Thiobarbituric acid reactive substances (TBARS), the enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and copper (Cu) and zinc (Zn) levels were estimated in the erythrocytes of 25 non-metastatic prostate cancer patients, 36 benign prostatic hyperplasia (BPH) patients and 24 age- and sex-matched healthy subjects (controls). RESULTS: TBARS concentrations were significantly increased, while erythrocyte GPX and SOD activities were significantly decreased in the prostate cancer group versus controls (P < 0.001) and BPH group (P < 0.05). Zn levels were lowered in prostate cancer patients versus controls (P < 0.01) with no significant changes between BPH and cancer groups. Similarly, lipid peroxidation was increased (P < 0.05) with decreased SOD activity and Zn level (P < 0.05) in BPH versus controls. CONCLUSION: These results reveal an alteration in the lipid peroxidation index, with concomitant changes in the antioxidant defense system in prostate cancer patients compared to BPH patients. We hypothesize that an altered prooxidant-antioxidant balance may lead to an increase in oxidative damage and consequently may play an important role in prostate carcinogenesis.

The effects of hyperbaric oxygen treatment on oxidative stress and SCE frequencies in humans.

OBJECTIVES: Hyperbaric oxygen (HBO) therapy is a useful method for treatment of various clinical conditions but it can also cause an increased production of free radicals and oxidative DNA damage. In this study, our aim was to investigate the effects of hyperbaric oxygen on oxidative stress and genetic toxicity. DESIGN AND METHODS: Fifteen patients were exposed to HBO treatment for various pathologies related to hypoxia. Blood samples were taken before HBO therapy and at the end of the 1st, 10th and 20th HBO sessions. Antioxidant parameters and genetic toxicity were studied. RESULTS: We have observed that an increment of lymphocyte sister chromatid exchange (SCE) frequency was detected at the end of the 1st, 10th and 20th HBO sessions compared to before HBO treatment (P<0.05). No significant difference in erythrocyte copper-zinc superoxide dismutase (CuZn-SOD), selenium dependent glutathione peroxidase (SeGSH-Px) and malondialdehyde (MDA) levels were observed at the end of the 1st HBO therapy and the prolonged HBO exposure as compared to before HBO treatment (P>0.05). CONCLUSIONS: Our results indicate that HBO treatment did not cause significant changes on erythrocyte antioxidant capacity and lipid peroxidation; however, it could induce genotoxicity due to different mechanisms.

Evaluation of DNA damage using 3 comet assay parameters in workers occupationally exposed to lead.

The aim of this study was to investigate the association between DNA damage and blood lead levels in individuals occupationally exposed to lead. To evaluate this association, 61 workers exposed to lead were monitored in terms of DNA damage in blood lymphocytes. The levels of DNA damage were measured according to 3 comet assay parameters, including tail intensity (TI), tail moment (TM), and DNA tail (DNAt). A statistically significant positive correlation was found between the lead levels and TI, TM, and DNAt (p < .01). Smoking had independent effects on DNA damage. A statistically significant difference was observed between smokers and nonsmokers in regards to DNA damage parameters (p < .05). In addition, the lead and DNA damage levels in smokers were found to be significantly higher than the levels observed in nonsmoking workers (p < . 05). Our results show that exposure to lead induces genotoxic effects in peripheral lymphocytes, as measured by comet assays.

Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata.

Alopecia areata (AA) is an autoimmune inflammatory disease. However, little is known about the alterations in lipid peroxidation and antioxidant enzymes in the scalp of patients with AA. Therefore, the aim of this study was to investigate the status of oxidative stress in the scalp of patients with AA. We measured the levels of thiobarbituric acid reactive substances (TBARS) as lipid peroxidation status, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as antioxidant enzymes in the scalp of ten patients with AA and ten control subjects. The levels of TBARS in scalp of patients with AA (3654.1+/-621.2 nmol/g tissue) were significantly higher than those of controls (1210.2+/-188.8 nmol/g tissue) (P=0.002). The levels of SOD (134.8+/-23.8 U/g tissue) and GSH-Px (332.7+/-66.2 U/g tissue) in scalp of patients with AA were also significantly higher than those of controls (63.2+/-8.8 U/g tissue, 112.0+/-18.4 U/g tissue, respectively) (P=0.019, P=0.002, respectively). The mean levels of TBARS, SOD and GSH-Px in early phase of disease were increased 2-fold as compared with late phase of the disease. These results indicate that oxidative status is affected in AA. Lipid peroxidation and antioxidant enzymes may be involved in the pathogenesis of AA. Furthermore, we found high SOD and GSH-Px activities in the scalp of patient with AA. These high levels could not protect the patients against the reactive oxygen species, because lipid peroxidation could not be lowered in AA patients.

Increased oxidative stress and hypozincemia in male obesity.

OBJECTIVES: Antioxidants protect an organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Alterations in the levels of antioxidants and several essential trace elements in the plasma and various tissues of ob/ob mice have been reported previously. The aim of this study was to investigate oxidative status and trace elements in obese individuals. DESIGN AND METHODS: Seventy-six obese men (body mass index (BMI) > 30 kg/m(2)) and 24 healthy, age-matched male control volunteers were enrolled in the study. Fasting plasma insulin, glucose, triglyceride (TG), total cholesterol, VLDL, and HDL levels, erythrocyte glutathione peroxidase (GSH-Px) and copper zinc-superoxide dismutase (CuZn-SOD) activities, and erythrocyte thiobarbituric acid reactive substances (TBARS) levels were measured in both groups. Erythrocyte copper (Cu), zinc (Zn) and iron (Fe) levels were also measured. RESULTS: We found that the mean Cu and Fe levels in obese individuals were not significantly different than those in the control group, whereas the mean Zn levels were significantly lower than those of the control group (p = 0.023). The mean erythrocyte CuZn-SOD and GSH-Px levels in obese individuals were significantly lower than those in controls (p = 0.001) whereas erythrocyte TBARS levels were significantly higher (p = 0.001) than those of the control group. CONCLUSION: We conclude that male obesity is associated with defective antioxidant status and hypozincemia, which may have implications in the development of obesity related health problems.

Oxidative stress and antioxidant capacity in patients with inflammatory bowel disease.

OBJECTIVES: In this study we aimed to determine the levels of Glutathione peroxidase (GSH-Px) and Malondialdehyde (MDA) in patients with inflammatory bowel disease (IBD) to investigate their contribution to tissue injury in inflammatory bowel disease. DESIGN AND METHODS: Forty-seven GSH-Px patients (35 with ulcerative colitis and 12 with Crohn's disease) and 30 healthy controls were included in the study. Their plasma and MDA levels were compared using nonparametric statistical methods. RESULTS: Plasma GSH-Px levels of the patients group were significantly higher than the control group (p < 0.001). There was no significant difference between patients and controls in view of plasma levels of MDA. CONCLUSIONS: High levels of GSH-Px, which is response against oxidative stress, indicates the increase of free radicals in IBD, while normal plasma MDA levels suggest the clearance of free radicals without leading to lipid peroxidation. Our result reveals that there is an existing antioxidant capacity despite oxidative stress in patients with IBD.

Effects of halothane, enflurane, and isoflurane on plasma and erythrocyte antioxidant enzymes and trace elements.

Alterations of the normal redox balance in mammals might be attributed to increases of plasma free-radical concentrations and/or a disruption of the protective mechanisms. These conditions lead to damage to cellular structure by the mechanism of lipoperoxidation, particularly in the liver, kidney, and central nervous system. In this study, the effect of general anesthesia on the oxidative metabolism of human plasma and erythrocytes was investigated. Forty-five patients undergoing anesthesia by using halothane, enflurane, or isoflurane were included in this study. Blood samples were taken preoperatively, the first hour, the first day, and the third day after the operation. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities and trace elements such as cofactor copper (Cu), zinc (Zn) and selenium (Se) levels were measured in plasma and red blood cells. Our results showed that halothane and enflurane administration increased the plasma GSH-Px activity and reduced zinc levels. In addition, they lowered SOD and GSH-Px activities and trace element levels on erythrocytes. Isoflurane had no effect on plasma antioxidant enzymes, but, similar to the others, isoflurane decreased the plasma zinc levels, erythrocyte SOD and GSH-Px activities and trace element levels.

Selenium and zinc levels in volatile substance abusers.

Plasma and erythrocyte levels of selenium (Se) and zinc (Zn) have not been investigated in volatile (inhalant) substance abusers previously, although changes in the activities of antioxidant enzymes resulting from oxidative damage caused by various constituents of volatile substances have been shown in a few animal and human studies. Concentrations of these two elements in erythrocytes and plasma of 37 adolescents with inhalant abuse were measured by atomic absorption spectrophotometry and compared with those of 37 age-matched healthy controls. Erythrocyte and plasma levels of Se and plasma level of Zn were significantly lower in the study group when compared to the control group. Chronic inhalation of volatile substances can decrease the plasma levels of Se and Zn and, thus, may lead to a decrease in the activity of antioxidant enzyme systems in adolescent abusers. The role of Se and Zn supplementation in children with inhalant abuse remains to be determined considering the reduced antioxidant activity resulting from deficiency of these trace elements.

The effect of relaparotomy timing on wound healing in an animal model.

BACKGROUND: The effect of the timing of the second laparotomy on wound healing is not clear. In an experimental study in rats, we aimed to investigate the effect of timing on wound healing after reoperations on the same surgical site. MATERIAL AND METHODS: Forty-eight rats were divided into four groups. The control group (GC) didn't have another laparotomy whereas the relaparotomies on the same surgical site were performed either on the 3rd, 15th or the 30th postoperative days in the three study groups (G3, G15, G30 respectively). The midline tension pressure, collagen types I, III and, histological analysis were performed from the specimens in order to assess the wound healing and strength. RESULTS: The tensile strength was the highest in GC and decreased gradually in G3, G15 and G30, the difference between the groups did not reach statistical significance. Higher collagen levels, increased fibrosis, and large defects were observed in relaparotomy groups than CG. The musculoaponeurotic gap was shortest in GC when compared to other three relaparotomy groups (P < 0.001) and, it was the longest in G30 (P = 0.004 between G3 and G30). CONCLUSIONS: Although non-statistically significant the gradual decrease in the tensile strength and the statistically significant increase in the musculoaponeurotic gap with time point out the importance of the timing of relaparotomy in the healing process. Early relaparotomies do not disrupt the healing process as much as relaparotomy performed later.

Effects of smoking during pregnancy on DNA damage and ROS level consequences in maternal and newborns' blood.

Some of the genotoxic/carcinogenic substances or metabolites in cigarette smoke are capable of passing through the placenta and harming a newborn's health. Smoking is also known as a factor in the formation of oxidative damage and the main mechanism involved in the carcinogenic process. Predetermining this genotoxic risk can be successfully achieved by measuring certain parameters of oxidative stress. The comet assay is considered an important biomarker for the evaluation of genotoxic substances and is effective for detecting DNA damage caused by smoking. This study examined third trimester bloods and the cord blood of 28 actively smoking and 22 non-smoking mothers in terms of DNA damage and oxidative stress parameters. Cu/Zn superoxide dismutase (CuZn-SOD), malondialdehyde (MDA), catalase (CAT), plasma nitrite/nitrates (NO2-/NO3-), selenium-dependent glutathione peroxidase (Se-GPx), Cu, and Zn levels were measured as indicators of oxidative damage. There were no significant increases in DNA damage of the actively smoking pregnant group in comparison with the non-smoking pregnant group, either in the third trimester or cord blood. Oxidative stress parameters of smoker and non-smoker groups were statistically different for MDA (p<0.05), CuZn-SOD (p<0.01), Se-GPx (p<0.05) values while the difference was not significant for NO2-/NO3-, CAT, Zn, and Cu values. The same values were also investigated in cord blood,and only NO2/NO3-(p<0.01), Se-GPx (p<0.01 and CAT (p<0.001) values were found statistically different.Smoking mothers may have been exposed to more oxidative stress than non-smoking mothers

Induced antioxidant activity in hospital staff occupationally exposed to ionizing radiation.

PURPOSE: Occupational exposure to low levels of ionizing radiation (IR) in radiology department staff may affect their antioxidant status. The aim of this study was to evaluate the oxidative stress parameters in radiology staff that are occupationally exposed to IR in a hospital setting. MATERIALS AND METHODS: The study population included 40 exposed radiology staff and 30 control subjects. The radiation doses of exposed staff ranged between 0.10 and 3.8 milligray (mGy) per month. The subjects' antioxidant status was determined by measuring the activities of copper zinc-superoxide dismutase (CuZn-SOD), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) enzymes, and the levels of malondialdehyde (MDA) in erythrocytes. RESULTS: Our results showed that the activities of erythrocyte CuZn-SOD and Se-GPx enzymes observed for the radiation exposed group were significantly higher than in the controls. The activity of CAT enzyme and MDA levels were significantly lower in the exposed group than in the controls. Moreover, we investigated the influence of confounding factors on antioxidant enzymes or lipid peroxidation (LP), but we could not find any associations between them. CONCLUSIONS: Our study indicates the presence of stimulant effect of chronic low-dose radiation in exposed individuals, resulting in enhanced resistance to oxidative stress.

Toxic metals in breast milk samples from Ankara, Turkey: assessment of lead, cadmium, nickel, and arsenic levels.

Toxic metals are one of the significant groups of chemical contaminants that humans are exposed to by oral, inhalation, and dermal routes. Exposure to these chemicals begins with intrauterine life and continues during lactation period at the first years of life. Breastfeeding has a much more special place than other nutrition options for infants. However, when possibility of contaminant transfer by breast milk is considered, its safety and quality is essential. Regarding infant and mother health and limited number of information on this field in Turkey, measuring contamination levels in breast milk is important. Therefore, in the present study, lead (Pb), cadmium (Cd), nickel (Ni), and arsenic (As) levels were measured by atomic absorption spectrometry in 64 breast milk samples obtained from mothers from Ankara, Turkey. Pb and Ni levels in breast milk samples were found to be 391.45±269.01 µg/l and 43.94±33.82 µg/l (mean ± SD), respectively. Cd was found only in one of 64 samples, and the level was 4.62 µg/l. As level was below the limit of quantification (LOQ, 7.6 µg/l) in all samples. These findings will accurately direct strategies and solutions of protection against contaminants in order to reduce their levels in biological fluids.

Role of midkine in cadmium-induced liver, heart and kidney damage.

Accumulation of the widespread environmental toxin cadmium (Cd) in tissues results in toxicity. Cd, which can induce a broad spectrum of biological effects, is a toxic substance and is associated with inflammation and apoptosis. Midkine (MK) has fibrinolytic, antiapoptotic, transforming, angiogenetic and chemotactic activities. After Cd toxicity, we found increased MK expression in liver cells in an in vitro cell culture model. The aim of this study was to determine the possibility of relationship between tissue MK expression levels, tumor necrosis factor α(TNF-α) levels and apoptosis in a chronic Cd toxicity model in rats. Male Wistar rats were exposed to Cd at the dose of 15 parts per million (ppm) for 8 weeks. MK levels were measured in kidney, heart and liver tissue by enzyme-linked-immunosorbent assay (ELISA). MK messenger RNA (mRNA) expression was evaluated by RT-PCR. Tissue apoptosis level was evaluated with tissue caspase-3 activity levels. Accumulation of Cd in liver is higher than the kidney and heart. Cd-treated rats had significantly higher tissue TNF-α and caspase-3 levels when compared with the control rats (p < 0.001). MK mRNA and protein levels were also significantly upregulated in the Cd-treated group (p < 0.05, p < 0.001, respectively). When compared with apoptosis in tissues, it was more prominent in the liver than kidney and heart. MK level is found increased 3, 1.7 and 1.3× folds in liver, kidney and heart, respectively. Our results showed that chronic Cd administration induces inflammation and apoptosis in rat liver, kidney and heart. MK involved in damage mechanisms of Cd-induced tissues. Further studies will show the underlying mechanism of increased MK expression in Cd toxicity.