Determination of Heavy Metal Content: Arsenic, Cadmium, Mercury, and Lead in Cyano-Phycocyanin Isolated from the Cyanobacterial Biomass.

Cyano-phycocyanin (C-PC) is a light-absorbing biliprotein found in cyanobacteria, commonly known as blue-green algae. Due to its antioxidative, anti-inflammatory, and anticancer properties, this protein is a promising substance in medicine and pharmaceuticals. However, cyanobacteria tend to bind heavy metals from the environment, making it necessary to ensure the safety of C-PC for the development of pharmaceutical products, with C-PC isolated from naturally collected cyanobacterial biomass. This study aimed to determine the content of the most toxic heavy metals, arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in C-PC isolated from different cyanobacterial biomasses collected in the Kaunas Lagoon during 2019-2022, and compare them with the content of heavy metals in C-PC isolated from cultivated Spirulina platensis (S. platensis). Cyanobacteria of Aphanizomenon flos-aquae (A. flos-aquae) dominated the biomass collected in 2019, while the genus Microcystis dominated the biomasses collected in the years 2020 and 2022. Heavy metals were determined using inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS analysis revealed higher levels of the most investigated heavy metals (Pb, Cd, and As) in C-PC isolated from the biomass with the dominant Microcystis spp. compared to C-PC isolated from the biomass with the predominant A. flos-aquae. Meanwhile, C-PC isolated from cultivated S. platensis exhibited lower concentrations of As and Pb than C-PC isolated from naturally collected cyanobacterial biomass.

Effect of Organic Selenium on the Homeostasis of Trace Elements, Lipid Peroxidation, and mRNA Expression of Antioxidant Proteins in Mouse Organs.

(1) In this study we determined the effect of long-term selenomethionine administration on the oxidative stress level and changes in antioxidant protein/enzyme activity; mRNA expression; and the levels of iron, zinc, and copper. (2) Experiments were performed on 4-6-week-old BALB/c mice, which were given selenomethionine (0.4 mg Se/kg b.w.) solution for 8 weeks. The element concentration was determined via inductively coupled plasma mass spectrometry. mRNA expression of SelenoP, Cat, and Sod1 was quantified using real-time quantitative reverse transcription. Malondialdehyde content and catalase activity were determined spectrophotometrically. (3) After long-term SeMet administration, the amount of Se increased by 12-fold in mouse blood, 15-fold in the liver, and 42-fold in the brain, as compared to that in the control. Exposure to SeMet decreased amounts of Fe and Cu in blood, but increased Fe and Zn levels in the liver and increased the levels of all examined elements in the brain. Se increased malondialdehyde content in the blood and brain but decreased it in liver. SeMet administration increased the mRNA expression of selenoprotein P, dismutase, and catalase, but decreased catalase activity in brain and liver. (4) Eight-week-long selenomethionine consumption elevated Se levels in the blood, liver, and especially in the brain and disturbed the homeostasis of Fe, Zn, and Cu. Moreover, Se induced lipid peroxidation in the blood and brain, but not in the liver. In response to SeMet exposure, significant up-regulation of the mRNA expression of catalase, superoxide dismutase 1, and selenoprotein P in the brain, and especially in the liver, was determined.

Effect of Selenium on the Iron Homeostasis and Oxidative Damage in Brain and Liver of Mice.

Selenium is an essential trace element that maintains normal brain function, mainly due its antioxidant properties. Although the amount of Se in the body is tightly regulated by the liver, both an excess of and deficiency in Se can modulate the cellular redox status and affect the homeostasis of other essential elements for both humans and animals. The aim of this study was to determine the effect of inorganic selenium excess on oxidative stress and iron homeostasis in brain and liver of laboratory BALB/c mice, which were supplemented with Na2SeO3 solution (0.2 mg and 0.4 mg Se/kg body weight) for 8 weeks. The content of the lipid peroxidation product malondialdehyde and antioxidant enzyme catalase activity/gene expression were used as markers of oxidative damage and were evaluated by spectrophotometric assays. Selenium and iron concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Catalase gene expression was analyzed by qRT-PCR and ΔΔCt methods. Our results showed that doses of 0.2 mg Se and 0.4 mg Se caused a relatively low accumulation of Se in the brain of mice; however, it induced a 10-fold increase in its accumulation in the liver and also increased iron accumulation in both tested organs. Both doses of Se increased the content of malondialdehyde as well as decreased catalase activity in the liver, while the 0.4 mg Se dose has also activated catalase gene expression. Brain of mice exposed to 0.2 mg Se showed reduced lipid peroxidation; however, the exposure to 0.4 mg of Se increased the catalase activity as well as gene expression. One may conclude that exposure to both doses of Se caused the accumulation of this micronutrient in mice brain and liver and have also provided a disrupting effect on the levels of iron. Both doses of Se have triggered oxidative liver damage. In the brain, the effect of Se was dose dependent, where -0.2 mg of Se provided antioxidant activity, which was observed through a decrease in lipid peroxidation. On the contrary, the 0.4 mg dose increased brain catalase activity as well as gene expression, which may have contributed to maintaining brain lipid peroxidation at the control level.

Alzheimer's Disease Association with Metals and Metalloids Concentration in Blood and Urine.

As there is some evidence that the risk for Alzheimer's disease (AD) is partially attributable to environmental exposure to some metals and metalloids, we examined an association between AD and arsenic, chromium, and selenium in 53 AD patients and 217 controls. Urinary arsenic, blood chromium, and selenium were determined by inductively coupled plasma mass spectrometry. Logistic regression models calculating odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate AD association with arsenic, chromium, and selenium. In AD patients, urinary arsenic and blood chromium were significantly higher, while blood selenium was significantly lower compared to controls. Increased blood selenium was related to a significant decrease in the odds of AD after adjustment for risk factors. Blood selenium per 1 kg × 10-9/m3 × 10-4 increment was associated with 1.4 times lower risk of AD (OR = 0.71; 95% CI 0.58-0.87). A significant increase in the odds of AD associated with increased blood chromium was also seen in the adjusted model: the OR per 1 kg × 10-9/m3 × 10-3 chromium increment was 2.39 (95% CI 1.32-4.31). The association of urinary arsenic with the risk of AD was not significant. The data obtained provide evidence that selenium reduces the risk of Alzheimer's disease, while chromium increases it.

Effect of Zinc on the Oxidative Stress Biomarkers in the Brain of Nickel-Treated Mice.

The overexposure to nickel due to the extensive use of it in modern technology remains a major public health concern. The mechanisms of pathological effects of this metal remain elusive. The present study was devoted to evaluate the effect of nickel on the oxidative state of the brain cells of mice and to assess whether zinc as redox state modulator could efficiently protect cells against nickel's neurotoxicity. As oxidative stress biomarkers in the present study, we have measured the concentrations of reduced glutathione, metallothioneins, and malondialdehyde and the activity of the enzyme δ-aminolevulinate dehydratase. For the single metal exposure, mice were i.p. injected once with solutions of NiCl2 and/or ZnSO4; repeated exposure was performed i.p. injecting metal salt solutions for 14 days (once a day). The control mice received i.p. injections of saline. Results of our study demonstrate that single and 14 days of Ni2+ exposure decreased reduced glutathione and increased malondialdehyde contents in the brain of mice. Repeated Ni2+ administration significantly inhibited δ-aminolevulinate dehydratase while increasing brain metallothionein concentration at both exposure periods. Zinc exhibited a protective effect against nickel-induced glutathione and lipid peroxidation in brain cells of mice at both intervals of time, while repeated exposure to this metal significantly raised the brain metallothionein content. Repeated Zn2+ pretreatment protected δ-aminolevulinate dehydratase from Ni2+-induced inhibition and significantly increased metallothionein concentration at both investigated time intervals.

Cadmium Exposure and Risk of Breast Cancer by Histological and Tumor Receptor Subtype in White Caucasian Women: A Hospital-Based Case-Control Study.

As the majority of experimental studies suggest cadmium being metalloestrogen, we examined cadmium/breast cancer (BC) association by histological and tumor receptor subtype in 509 invasive BC patients and 1170 controls. Urinary cadmium was determined by atomic absorption spectrometry, and categorized using tertiles of its distribution in the controls: <0.18, 0.18-0.33, >0.33 kg × 10-9/kg × 10-3 creatinine. Relative to the lowest category of urinary cadmium adjusted odds ratio (OR) of ductal BC was 1.18 (95% confidence interval (CI): 0.89-1.58) in the intermediate and 1.53 (95% CI: 1.15-2.04) in the highest category. There was a significant association for hormone receptor-positive ductal BC: ORs per category increase were 1.34 (95% CI: 1.14-1.59) for estrogen receptor-positive (ER+), 1.33 (95% CI: 1.09-1.61) for progesterone receptor-positive (PR+) and 1.35 (95% CI: 1.11-1.65) for ER+/PR+ BC. We found a significant association between cadmium and human epidermal growth factor receptor 2-negative (HER2-) ductal BC. The strongest association with cadmium was for ER+/PR+/HER2- ductal BC. The associations between cadmium and lobular BC with hormone receptor-positive and HER2- were positive but insignificant. There was no evidence that the associations with cadmium differed for cancers with different tumor histology (p-heterogeneity > 0.05). This study provides evidence that urinary cadmium is associated with the risk of hormone receptor-positive and HER2- breast cancer independent of tumor histology.

Post-exposure distribution of selenium and aluminum ions and their effects on superoxide dismutase activity in mouse brain.

The study was conducted to determine how aluminum (Al) and selenium (Se) ions alone and in combination affect superoxide dismutase (SOD) activity and to evaluate the distribution of these elements in the blood and the brain of laboratory mice. SOD activity in mouse brain was evaluated after single-time (within 24 h) and repeated (over 14 days) intraperitoneal (IP) injections of SeO32-, Al3+, and (SeO32-+Al3+) solutions. The control mice received IP injections of the same volume of saline. Aluminum concentration in mouse blood increased both after single-time and repeated injections of AlCl3 and the combined (AlCl3 + Na2SeO3) solutions. The concentration of Se increased in blood after single-time and repeated injections of Na2SeO3 and the combined (AlCl3 + Na2SeO3) solutions. After the single-time injection of the experimental solutions, the concentrations of both Al and Se in mouse brain remained at baseline, but after repeated injections of (AlCl3 + Na2SeO3) solutions increased aluminum concentration. A single IP injection of Al did not change SOD activity in mouse brain, while a single injection of Se or the Se + Al mixture decreased it. After 14 days, IP injections of Al or Se alone did not affect SOD activity, while their combination decreased it. Our results showed that Se ions decreased SOD activity in mouse brain after both single-time and repeated IP injections of selenium-containing solutions. The study failed to show a direct or linear effect of increased Al or Se concentrations on SOD activity in mouse brain.

Correlation of magnesium deficiency with C-reactive protein in elective cardiac surgery with cardiopulmonary bypass for ischemic heart disease.

BACKGROUND AND OBJECTIVE: Cardiac surgery is associated with systemic inflammatory response, which is triggered by cardiopulmonary bypass (CPB) and possibly with underlying magnesium deficiency. Animal studies have shown that magnesium deficiency intensifies oxidative stress and inflammatory processes. We aimed to find a link between serum, erythrocyte, cardiac tissue magnesium concentration and C-reactive protein (CRP) as an inflammatory marker in patients undergoing elective cardiac surgery with CPB. MATERIALS AND METHODS: The data of 27 patients undergoing elective cardiac surgery with CPB for ischemic heart disease were analyzed. Measurements were taken at the baseline, i.e., 24 h before surgery (serum magnesium, CRP); time point 1, before CPB (serum, erythrocyte and cardiac tissue magnesium); time point 2, after CPB (serum, erythrocyte and cardiac tissue magnesium), and time point 3, 15-17 h after surgery (serum, erythrocyte magnesium, CRP). RESULTS: There was a negative correlation between baseline serum magnesium and baseline CRP (P=0.009; r=-0.492), negative correlation between cardiac tissue magnesium at the time point 1 and baseline CRP (P=0.021; r=-0.443), and positive correlation between CRP at time point 3 and erythrocyte magnesium at time point 2 (P<0.001; r=0.637). CONCLUSIONS: The data of our study verify that inflammatory marker CRP and magnesium concentration in serum and cardiac tissue before the surgery are inversely related in patients undergoing elective cardiac surgery with CPB. Well-planned further studies are needed to evaluate the importance of underlying magnesium deficiency on the severity of systemic inflammatory response and postoperative complications after surgery with CPB.

Association between cadmium and breast cancer risk according to estrogen receptor and human epidermal growth factor receptor 2: epidemiological evidence.

The study aimed to examine the association between cadmium (Cd) and the risk of breast cancer according to estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). A hospital-based case-control study was carried out in 585 cases and 1,170 controls. Information on possible risk factors was collected via a structured questionnaire. Urinary Cd was determined by atomic absorption spectrometry. The ER and HER2 levels in tumor tissue were analyzed by immunohistochemistry. Logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for breast cancer by creatinine-adjusted urinary Cd. Women with greater creatinine-adjusted urine Cd (3rd quartile: 0.241-0.399 µg/g and 4th quartile: ≥ 0.4 µg/g) experienced 1.6 times higher risk of breast cancer compared with those having Cd concentration lower than 0.147 µg/g (1st quartile) [OR = 1.6, (95 % CI 1.19, 2.17) and OR = 1.62 (95 % CI 1.19, 2.21), respectively, P trend = 0.001] after adjustment for age and other confounders. Both ER+ and HER2- cases from the highest quartile of urine Cd exhibited approximately twice the breast cancer risk of those in the lowest quartile [OR = 1.9, (95 % CI 1.31, 2.74) and OR = 1.87, (95 % CI 1.33, 2.62), respectively, P trend <0.001) after adjustment for confounders. The data support cadmium as a risk factor for breast cancer, especially for both ER+ and HER2- cancer patients.

Cadmium concentration in biological media of breast cancer patients.

The study aimed to determine and compare cadmium (Cd) concentration in different biological media of breast cancer and benign breast tumor patients. Concentration of Cd was determined in breast tissue, urine, and blood of 57 breast cancer and 51 benign tumor patients. Two samples of breast tissue from each patient, i.e., tumor and healthy tissue were taken for the analysis. Cd in biological media was determined by atomic absorption spectrometry (Perkin-Elmer, Zeeman 3030). The mean Cd concentration in breast cancer patients was 0.053 µg/g (95% confidence intervals, CI 0.042-0.065) for tumor sample and 0.02 µg/g (95% CI 0.014-0.026) for healthy breast tissue sample (P < 0.001). In benign tumor patients, the figures were as follows: 0.037 µg/g (95% CI 0.023-0.051) and 0.032 µg/g (95% CI 0.018-0.047) (P > 0.05). Cd content in malignant tumor significantly differed from that in benign tumor (P < 0.01). Cancer patients with positive estrogen receptors (ERs) had significantly greater concentration of breast tissue Cd compared to patients with negative ERs (P = 0.035). Adjusted for creatinine, Cd in urine was significantly higher in cancer patients than in controls (P < 0.001). In cancer patients, a positive Spearman's correlation was found between Cd in tumor and healthy breast tissue, blood (r = 0.44 and r = 0.39, respectively, P < 0.01). Correlation between Cd in urine of cancer patients and number of cigarettes smoked during lifetime was suggestive (r = 0.59, P = 0.075). The data obtained show higher concentration of cadmium in breast tumor and urine of cancer patients and support a possible relationship between cadmium and breast cancer.