Developmental exposure to cobalt chloride affected mouse testis via altered iron metabolism in adulthood.

INRODUCTION: Cobalt (Co) is known to interfere with iron (Fe) metabolism that is essential for differentiating male germ cells. Our aim was to study the effect of developmental chronic cobalt exposure on mouse testis through changes in iron homeostasis in adulthood. METHODS: Pregnant ICR mice were exposed to 75 mg (low dose) or 125 mg (high dose)/kg b.w. cobalt chloride (CoCl2) with drinking water for 3 days before delivery and treatment continued until postnatal day 90 of the pups. Age-matched control animals obtained regular tap water. Testes of control and Co-treated mice were processed for immunohistochemistry and inductively coupled plasma mass spectrometry. Sperm count was performed. RESULTS: Chronic CoCl2 administration resulted in significant dose-dependent Co accumulation in sera and testes of the exposed mice. Fe content also showed a significant increase in sera and testes compared to the untreated controls. Surprisingly, testes of low dose-treated mice had ∼ 2.7-fold higher Fe content compared to those exposed to the high dose. A significant dose-dependent reduction in relative testis weight by 18.8% and by 37.7% was found after treatment with low and high dose CoCl2, respectively was found. Our study demonstrated that developmental chronic exposure to CoCl2 affected cellular composition of the testis manifested by germ cell loss and low sperm count, accompanied by altered androgen response in Sertoli cells (loss of stage-specific expression of androgen receptor). A possible mechanism involved is iron accumulation in the testis that was associated with altered ferroportin-hepcidin localization in seminiferous tubules depleted in germ cells. As a protective mechanism for germ cells in condition of iron excess, ferroportin was distributed in Sertoli cells around elongating spermatids. Similar changes in expression of transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) implied that both factors of testicular Fe homeostasis are closely related. Outside the seminiferous tubules, Leydig cells localized ferroportin, hepcidin, DMT1 and TfR1 thus they could be considered as a main site for iron metabolism. CONCLUSION: Our data suggest that Co exerts its effects on the testis by indirect mechanism possibly through alteration in Fe homeostasis.

A review of the epidemiological and laboratory evidence of the role of aluminum exposure in pathogenesis of cardiovascular diseases.

The objective of the present study was to review the epidemiological and laboratory evidence on the role of aluminum (Al) exposure in the pathogenesis of cardiovascular diseases. Epidemiological data demonstrated an increased incidence of cardiovascular diseases (CVD), including hypertension and atherosclerosis in occupationally exposed subjects and hemodialysis patients. In addition, Al body burden was found to be elevated in patients with coronary heart disease, hypertension, and dyslipidemia. Laboratory studies demonstrated that Al exposure induced significant ultrastructural damage in the heart, resulting in electrocardiogram alterations in association with cardiomyocyte necrosis and apoptosis, inflammation, oxidative stress, inflammation, and mitochondrial dysfunction. In agreement with the epidemiological findings, laboratory data demonstrated dyslipidemia upon Al exposure, resulting from impaired hepatic lipid catabolism, as well as promotion of low-density lipoprotein oxidation. Al was also shown to inhibit paraoxonase 1 activity and to induce endothelial dysfunction and adhesion molecule expression, further promoting atherogenesis. The role of Al in hypertension was shown to be mediated by up-regulation of NADPH-oxidase, inhibition of nitric oxide bioavailability, and stimulation of renin-angiotensin-aldosterone system. It has been also demonstrated that Al exposure targets cerebral vasculature, which may be considered a link between Al exposure and cerebrovascular diseases. Findings from other tissues lend support that ferroptosis, pyroptosis, endoplasmic reticulum stress, and modulation of gut microbiome and metabolome are involved in the development of CVD upon Al exposure. A better understanding of the role of the cardiovascular system as a target for Al toxicity will be useful for risk assessment and the development of treatment and prevention strategies.

Djulis Hull Enhances the Efficacy of Ferric Citrate Supplementation via Restoring Normal Iron Efflux through the IL-6-Hepcidin-Ferroportin Pathway in High-Fat-Diet-Induced Obese Rats.

Obesity-related functional iron disorder remains a major nutritional challenge. We evaluated the effects of djulis hull (DH) on iron metabolism in 50% high-fat-diet-induced obese rats supplemented with ferric citrate (2 g iron/kg diet) for 12 weeks. DH supplementation (5, 10, 15% dry weight/kg diet) significantly increased serum and hepatic iron but decreased appetite hormones, body weight, hepcidin, and liver inflammation (all p < 0.05). The Spearman correlation showed that appetite hormones were negatively associated with iron but positively correlated with liver hepcidin (all p < 0.05). A Western blot analysis showed that DH significantly downregulated hepatic hepcidin through the IL-6-JAK-STAT3 and enhanced ferroportin (Fpn) via the Keap1-Nrf2 and PHD2-HIF-2α. An in vitro study revealed that major bioactive compounds of DH, hexacosanol, and squalene suppressed LPS-induced IL-6 and hepcidin but enhanced Fpn expression in activated THP-1 cells. In conclusion, DH may exert nutraceutical properties for the treatment of functional iron disorder and restoration of iron efflux may have beneficial effects on weight control.

Dissecting the role of cadmium, lead, arsenic, and mercury in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

The objective of the present study was to review the existing epidemiological and laboratory findings supporting the role of toxic metal exposure in non-alcoholic fatty liver disease (NAFLD). The existing epidemiological studies demonstrate that cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) exposure was associated both with an increased risk of NAFLD and altered biochemical markers of liver injury. Laboratory studies demonstrated that metal exposure induces hepatic lipid accumulation resulting from activation of lipogenesis and inhibition of fatty acid ß-oxidation due to up-regulation of sterol regulatory element-binding protein 1 (SREBP-1), carbohydrate response element binding protein (ChREBP), peroxisome proliferator-activated receptor γ (PPARγ), and down-regulation of PPARα. Other metabolic pathways involved in this effect may include activation of reactive oxygen species (ROS)/extracellular signal-regulated kinase (ERK) and inhibition of AMP-activated protein kinase (AMPK) signaling. The mechanisms of hepatocyte damage during development of metal-induced hepatic steatosis were shown to involve oxidative stress, endoplasmic reticulum stress, pyroptosis, ferroptosis, and dysregulation of autophagy. Induction of inflammatory response contributing to progression of NAFLD to non-alcoholic steatohepatitis (NASH) upon toxic metal exposure was shown to be mediated by up-regulation of nuclear factor κB (NF-κB) and activation of NRLP3 inflammasome. Moreover, epigenetic effects of the metals, as well as their effect on gut microbiota and gut wall integrity were also shown to mediate their role in NAFLD development. Despite being demonstrated for Cd, Pb, and As, the contribution of these mechanisms into Hg-induced NAFLD is yet to be estimated. Therefore, further studies are required to clarify the intimate mechanisms underlying the relationship between heavy metal and metalloid exposure and NAFLD/NASH to reveal the potential targets for treatment and prevention of metal-induced NAFLD.

Medical application of laser-induced breakdown spectroscopy (LIBS) for assessment of trace element and mineral in biosamples: Laboratory and clinical validity of the method.

BACKGROUND: Biomedical application is based on the use of LIBS-derived data on chemical contents of tissues in diagnosis of diseases, forensic investigation, as well as a mechanism for providing online feedback for laser surgery. Although LIBS has certain advantages, the issue of correlation of LIBS-derived data on chemical element content in different human and animal tissues with other methods, and especially ICP-MS, remains pertinent. The objective of the present review was to discuss the application of laser-induced breakdown spectroscopy (LIBS) for elemental analysis of human biosamples or tissues from experimental models of human diseases. METHODS: A systematic search in the PubMed-Medline, Scopus, and Google Scholar databases using the terms laser-induced breakdown spectroscopy, LIBS, metals, trace elements, minerals, and names of particular chemical elements was performed up through 25 February, 2023. Of all extracted studies only those dealing with human subjects, human tissues, in vivo animal and in vitro cell line models of human diseases were reviewed in detail. RESULTS: The majority of studies revealed a wide number of metals and metalloids in solid tissues including teeth (As, Ag, Ca, Cd, Cr, Cu, Fe, Hg, Mg, Ni, P, Pb, Sn, Sr, Ti, and Zn), bones (Al, Ba, Ca, Cd, Cr, K, Mg, Na, Pb, Sr), and nails (Al, As, Ca, Fe, K, Mg, Na, P, Pb, Si, Sr, Ti, Zn). At the same time, LIBS was also used for estimation of trace element and mineral content in hair (Ca, Cu, Fe, K, Mg, Na, Zn), blood (Al, Ca, Co, Cd, Cu, Fe, Mg, Mn, Ni, Pb, Si, Sn, Zn), cancer tissues (Ca, Cu, Fe, Mg, K, Na, Zn) and other tissues. Single studies revealed satisfactory correspondence between quantitative LIBS and ICP-OES/MS data on the level of As (81-93 %), Pb (94-98 %), Cd (50-94 %) in teeth, Cu (97-105 %), Fe (117 %), Zn (88-117 %) in hair, Ca (97-99 %), Zn (90-95 %), and Pb (61-82 %) in kidney stones. LIBS also estimated specific patterns of trace element and mineral content associated with multiple pathologies, including caries, cancer, skin disorders, and other systemic diseases including diabetes mellitus type 2, osteoporosis, hypothyroidism, etc. Data obtained from in situ tissue LIBS analysis were profitably used for discrimination between tissue types. CONCLUSIONS: Taken together, the existing data demonstrate the applicability of LIBS for medical studies, although further increase in its sensitivity, calibration range, cross-validation, and quality control is required.

The role of hypoxia-inducible factor 1 alpha (HIF-1α) modulation in heavy metal toxicity.

Hypoxia-inducible factor 1 (HIF-1) is an oxygen-sensing transcriptional regulator orchestrating a complex of adaptive cellular responses to hypoxia. Several studies have demonstrated that toxic metal exposure may also modulate HIF-1α signal transduction pathway, although the existing data are scarce. Therefore, the present review aims to summarize the existing data on the effects of toxic metals on HIF-1 signaling and the potential underlying mechanisms with a special focus on prooxidant effect of the metals. The particular effect of metals was shown to be dependent on cell type, varying from down- to up-regulation of HIF-1 pathway. Inhibition of HIF-1 signaling may contribute to impaired hypoxic tolerance and adaptation, thus promoting hypoxic damage in the cells. In contrast, its metal-induced activation may result in increased tolerance to hypoxia through increased angiogenesis, thus promoting tumor growth and contributing to carcinogenic effect of heavy metals. Up-regulation of HIF-1 signaling is mainly observed upon Cr, As, and Ni exposure, whereas Cd and Hg may both stimulate and inhibit HIF-1 pathway. The mechanisms underlying the influence of toxic metal exposure on HIF-1 signaling involve modulation of prolyl hydroxylases (PHD2) activity, as well as interference with other tightly related pathways including Nrf2, PI3K/Akt, NF-κB, and MAPK signaling. These effects are at least partially mediated by metal-induced ROS generation. Hypothetically, maintenance of adequate HIF-1 signaling upon toxic metal exposure through direct (PHD2 modulation) or indirect (antioxidant) mechanisms may provide an additional strategy for prevention of adverse effects of metal toxicity.

Polymorphisms of haptoglobin modify the relationship between dietary iron and the risk of gestational iron-deficiency anemia.

PURPOSE: To assess whether polymorphisms of haptoglobin (Hp) modify the relationship between dietary iron and the risk of gestational iron-deficiency anemia (IDA). METHODS: This study analyzed 1430 singleton pregnant women aged 20 ~ ≤ 48 years from the 2017-2019 National Nutrition and Health Survey of Pregnant Women in Taiwan. Sociodemographic, blood biochemical, Hp phenotype, and 24-h dietary recall data were collected. Erythropoiesis-related total prenatal supplementation was defined as the reported use of multivitamins and minerals, vitamin B complex, folate, and iron. RESULTS: Distributions of the Hp 1-1, Hp 2-1, and Hp 2-2 phenotypes were 13.6, 39.8, and 46.5%, respectively. Women with the Hp 1-1 phenotype had the lowest mean levels of serum ferritin (p-trend = 0.017), the highest prevalence of gestational ID (p-trend = 0.033) as well as the highest prevalence of gestational IDA (did not reach statistical differences, p-trend = 0.086). A gene-diet interaction on serum ferritin was observed between the Hp 1 and Hp 2 (2-1/2-2) alleles (p < 0.001). An adjusted multivariate logistic regression showed that compared to those with a normal blood iron status and who reported using erythropoiesis-related total prenatal supplements, those who did not had a 4.05-fold [odds ratio (OR) = 4.05 (95% confidence interval (CI) 2.63-6.24), p < 0.001] increased risk of gestational IDA. The corresponding ORs for carriers of the Hp 1 and Hp 2 alleles were 4.78 (95% CI 1.43-15.99) and 3.79 (95% CI 2.37-6.06), respectively. CONCLUSION: Pregnant women who are Hp 1 carriers are at increased risk for developing IDA if they do not meet the recommended dietary allowance for iron or use erythropoiesis-related prenatal supplements.

Iron overload and neurodegenerative diseases: What can we learn from Caenorhabditis elegans?

Iron (Fe) is an essential trace element required for several physiological processes. It plays important roles in mitochondrial function, synthesis, and metabolism of the neurotransmitter, as well as oxygen transport. However, excess Fe can cause toxicity. Particularly, Fe overload may result in neurotoxicity, contributing to the development and progression of neurodegenerative diseases, although the molecular mechanisms underlying Fe-induced neurodegeneration have yet to be entirely understood. Alternative (non-rodent) experimental models have been pointed as important approaches to elucidate molecular and physiological events mediating Fe-induced pathology. Among such alternative strategies, an advantageous experimental worm-model system, Caenorhabditis elegans (C. elegans), has been used to investigate Fe-induced neurotoxicity and neurodegenerative disorders. Its genome has been fully sequenced, corroborating that it shares significant homology with mammalians, and has approximately 40% of human disease-related genes. As part of this review, we discuss studies using the C. elegans model to study molecular mechanisms such as oxidative stress, mitochondrial dysfunction, disturbed homeostasis, and its potential contribution to the study of metal-induced neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD).

Smoking is associated with altered serum and hair essential metal and metalloid levels in women.

The objective of the study was to evaluate the association between smoking and essential metal (Co, Cr, Cu, Fe, Mn, V, Zn) and metalloid (Se) levels in hair and serum of adult women using inductively coupled plasma-mass spectrometry (ICP-MS). In this cross-sectional study, a total of 344 women 20-70 years old including 199 smokers and 145 non-smoking women were enrolled. Serum Cu, Fe, and Zn levels in smoking women were found to be 6%, 8%, and 3% lower of levels in non-smokers, respectively. In contrast, circulating Mn, V, and especially Cr concentrations in smoking women exceeded the respective values in non-smoking women by 5%, 14%, and 54%. Hair Fe and Se levels in smoking women were 17% and 23% lower as compared to non-smoking controls, respectively. In multiple regression models, smoking severity was inversely associated with serum and hair Se concentrations, whereas the relationship to serum and hair Cr was positive. In addition, serum Zn and hair Fe levels were found to be inversely associated with the number of cigarettes per day. These findings hypothesize that health hazards of smoking may be at least in part be mediated by alteration in essential metal and metalloid metabolism.

Mercury and cancer: Where are we now after two decades of research?

The present study aims to review epidemiological and experimental toxicology studies published over the last two decades linking mercury (Hg) exposure and carcinogenesis, with a special emphasis on the potential underlying mechanisms. While some epidemiological studies have observed a strong association between environmental/occupational Hg exposure levels, measured in blood, toenail, and hair, and cancer risk and mortality, others failed to reveal any association. In experimental models, high-dose Hg exposure has been linked with cytotoxicity, whereas low-dose exposure was posited to induce proliferative responses in both normal and cancerous cells by interference with estrogen receptor, ERK1/2, JNK, NADPH-oxidase and, potentially, Nrf2 signaling. Combined with reduced apoptosis and pro-survival signaling upon low-dose Hg exposure, accumulation of DNA lesions in cells may predispose to an increased risk of malignant transformation. In addition, the pro-oxidant activity of Hg species may induce oxidative DNA modifications and inhibits DNA repair mechanisms. Furthermore, epigenetic effects of Hg exposure seem to contribute to the carcinogenic activity, although the particular mechanisms have yet to be characterized. Therefore, even after 20 years of research, one cannot consider Hg as a non-carcinogenic agent, whereas specific mechanisms of Hg-induced toxicity may promote carcinogenic risk.

Lycium barbarum Polysaccharides and Capsaicin Inhibit Oxidative Stress, Inflammatory Responses, and Pain Signaling in Rats with Dextran Sulfate Sodium-Induced Colitis.

Ulcerative colitis (UC) is an inflammatory disease with chronic relapsing symptoms. This study investigated the effects of Lycium barbarum polysaccharides (LBP) and capsaicin (CAP) in dextran sulfate sodium (DSS)-induced UC rats. Rats were divided into normal, DSS-induced UC, and UC treated with 100 mg LBP/kg bw, 12 mg CAP/kg bw, or 50 mg LBP/kg bw and 6 mg CAP/kg bw. Rats were fed LBP or CAP orally by gavage for 4 weeks, and UC model was established by feeding 5% DSS in drinking water for 6 days during week 3. Oral CAP and mixture significantly reduced disease activity index. Oral LBP significantly decreased serum malondialdehyde, interleukin (IL)-6, colonic tumor necrosis factor (TNF)-α levels, and protein expression of transient receptor potential cation channel V1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1), but increased serum catalase activity. Oral CAP significantly suppressed serum IL-6, colonic TRPV1 and TRPA1 protein expression, but elevated IL-10 levels, serum superoxide dismutase and catalase activities. The mixture of LBP and CAP significantly reduced serum IL-6, colonic TNF-α and TRPA1 protein. In conclusion, administration of LBP and/or CAP attenuate DSS-induced UC symptoms through inhibiting oxidative stress, proinflammatory cytokines, and protein expression of TRPV1 and TRPA1.

Systemic Essential Metal and Metalloid Levels in Patients with Benign Breast Disease and Breast Cancer.

The objective of the present study is evaluation of serum and hair levels of essential metals and metalloids in women with benign breast disease and breast cancer in order to define similar and distinct patterns that may mediate the link between these pathologies. A total of 310 adult women aged 20-80 years old were enrolled in the present study. Of those, 103 patients had benign (fibrocystic) breast disease, 107 patients had breast cancer (stage II), and 100 women were healthy and with absence of breast pathology. Trace metal and metalloid levels in hair and serum were evaluated by inductively coupled argon plasma mass-spectrometry (ICP-MS). The data demonstrate that breast cancer patients were characterized by significantly higher hair Cr and V levels, as well as reduced Cu and Mn content as compared to both benign breast disease patients and controls. In contrast, serum Cu levels in women with breast cancer exceeded those in the controls and benign breast disease cases. Patients with both benign and malignant breast tumors were characterized by lower serum Mn levels as compared to the control values. Serum Cu/Zn and especially Cu/Mn were found to be significantly increased in cancer patients. Significantly reduced hair and serum Se levels were noted only in women with fibrocystic disease. Based on the analysis of two biosamples, it is proposed that malignant breast tumor development is associated with the reduction of systemic Mn and Zn levels, and a concomitant elevation of Cu concentrations.

Associations of Food and Nutrient Intake with Serum Hepcidin and the Risk of Gestational Iron-Deficiency Anemia among Pregnant Women: A Population-Based Study.

Hepcidin is a regulator of iron metabolism. Diet affects the body's iron status, but how it influences hepcidin concentrations and the risk of gestational iron-deficiency anemia (IDA) remains unclear. We investigated relationships of food and nutrient intake with serum hepcidin levels in relation to the iron status at a population scale. A retrospective cross-sectional study was conducted based on data obtained from the Nationwide Nutrition and Health Survey in pregnant women, Taiwan (2017~2020). In total, 1430 pregnant women aged 20~45 years with a singleton pregnancy were included. Data from blood biochemistry, 24-h dietary recall, and a food frequency questionnaire were collected during a prenatal checkup. Adjusted multivariate linear and logistic regression analyses were employed to measure the beta coefficient (ß) and 95% confidence interval (CI) of serum hepcidin and the odds ratio (OR) of IDA. In IDA women, serum hepcidin levels were positively correlated with the intake frequency of Chinese dim sum and related foods (ß = 0.037 (95% CI = 0.015~0.058), p = 0.001) and dark leafy vegetables (ß = 0.013 (0.001~0.025), p = 0.040), but they were negatively correlated with noodles and related products (ß = -0.022 (-0.043~-0.001), p = 0.038). An adjusted multivariate logistic regression analysis showed that dietary protein [OR: 0.990 (0.981~1.000), p = 0.041], total fiber [OR: 0.975 (0.953~0.998), p = 0.031], and rice/rice porridge [OR: 1.007 (1.00~1.014), p = 0.041] predicted gestational IDA. Total carbohydrates [OR: 1.003 (1.000~1.006), p = 0.036], proteins [OR: 0.992 (0.985~0.999), p = 0.028], gourds/shoots/root vegetables [OR: 1.007 (0.092~1.010), p = 0.005], and to a lesser extent, savory and sweet glutinous rice products [OR: 0.069 (0.937~1.002), p = 0.067] and dark leafy vegetables [OR: 1.005 (0.999~1.011), p = 0.088] predicted IDA. The risk of IDA due to vegetable consumption decreased with an increasing vitamin C intake (p for trend = 0.024). Carbohydrates and vegetables may affect the gestational iron status through influencing hepcidin levels. Vitamin C may lower the risk of gestational IDA due to high vegetable consumption.

Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer's Disease.

The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer's disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aß generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroinflammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aß cross-linking and up-regulation of RAGE expression. Moreover, Aß glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenuate the intracellular toxicity of the deranged tau and Aß, as well as inhibiting AGE accumulation and metal-induced neurotoxicity.

Hair Lead, Aluminum, and Other Toxic Metals in Normal-Weight and Obese Patients with Coronary Heart Disease.

The objective of the present study was to evaluate hair toxic metal levels in patients with obesity and/or coronary heart disease (CHD). Following a 2 × 2 factorial design, subjects without CHD were grouped into normal weight control (n = 123) and obese groups (n = 140). Patients suffering from CHD were divided into normal weight (n = 180) and obese CHD subjects (n = 240). Hair Al, As, Cd, Hg, Ni, and Pb levels were evaluated using inductively-coupled plasma mass-spectrometry. The data demonstrate that hair Al and Hg levels were higher in obese subjects as compared to normal weight controls. Normal weight CHD patients were characterized by significantly higher hair Al, As, Cd, and Pb levels when compared to healthy subjects. The highest hair Al, As, and Pb levels were observed in obese CHD patients, significantly exceeding the respective values in other groups. Factorial analysis revealed significant influence of factorial interaction (CHD*obesity) only for hair Pb content. Given the role of obesity as a risk factor for CHD, it is proposed that increased toxic metal accumulation in obesity may promote further development of cardiovascular diseases.

A follow-up study of mucociliary clearance and trace element and mineral status in children with chronic rhinosinusitis before and three months after endoscopic sinus surgery.

BACKGROUND: The existing data demonstrate the potential role of trace elements in nasal mucociliary clearance, although the association between trace element and mineral status and ciliary function in children with chronic rhinosinusitis is insufficiently studied. Therefore, the objective of the present study is evaluation of trace element and mineral status and mucociliary function in pediatric CRS patients before and after functional endoscopic sinus surgery. METHODS: The present study involved 30 children with chronic rhinosinusitis without nasal polyps. During this follow-up the patients were examined preoperatively (point 0), underwent functional endoscopic sinus surgery, and were repeatedly examined at three months postoperatively (point 1). At both points the patients were subjected to quality-of-life assessment using SNOT-20 questionnaire; endoscopic and computer tomography examination of the nasal sinuses; evaluation of ciliary function and mucosal cytology using high-speed videomicroscopy; assessment of blood count and inflammatory markers; as well as analysis of trace element and mineral levels in whole blood, serum, and hair using inductively-coupled plasma mass-spectrometry. RESULTS: The obtained data demonstrate that endoscopic sinus surgery significantly improved sinonasal pathology in children with chronic rhinosinusitis, as evidenced by significantly reduced Lund-Mackay, Lund-Kennedy, and SNOT-20 scores. At the same time, no significant improvement of ciliary functions or mucosal cytology was observed postoperatively. Trace element status assessment demonstrated that postoperative serum Zn, whole blood Mg and Cu were significantly lower as compared to preoperative values. In contrast, serum Mn and Cr, as well as whole blood Cr and hair Se were characterized by a significant increase at three months postoperatively. Multiple linear regression analysis demonstrated that serum Zn is significantly associated with the number of ciliated cells and cell viability, whereas serum Mn and whole blood Cu concentrations are inversely associated with cell viability and ciliary length, respectively. Hair Se was found to be associated with the number of neutrophils in the mucosa biopsy. CONCLUSION: Redistribution of trace elements and minerals may at least partially mediate prolonged recovery of mucosal ciliary function in children with chronic rhinosinusitis in three months after functional sinus surgery, although the particular mechanisms of these alterations in trace element levels are to be discovered.

Alteration of iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) tissue levels and speciation in rats with desferioxamine-induced iron deficiency.

The objective of the present study was to investigate the impact of iron deficiency and iron replenishment on serum iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn) speciation and tissue accumulation in a deferrioxamine-induced model of iron deficiency. A total of 26 male Wistar rats were divided into three groups: control; Fe-deficient; Fe-replenished (with iron (II) gluconate). Serum ferritin and transferrin levels were assessed using immunoturbudimetric method. Liver, spleen, and serum metal levels were assessed using ICP-MS. Speciation analysis was performed using a hyphenated HPLC-ICP-MS technique. Desferrioxamine injections resulted in a significant decrease in tissue iron content that was reversed by Fe supplementation. Iron speciation revealed a significant increase in serum transferrin-bound iron and reduced ferritin-bound Fe levels. Serum but not tissue Cu levels were characterized by a significant decrease in hypoferremic rats, whereas ceruloplasmin-bound fraction tended to increase. At the same time, Zn levels were found to be higher in liver, spleen, and serum of Fe-deficient rats with a predominant increase in low molecular weight fraction.Both iron-deficient and iron-replenished rats were characteirzed by increased transferrin-bound Mn levels and reduced low-molecular weight fraction. Hypothetically, these differences may be associated with impaired Fe metabolism under Fe-deficient conditions predisposing to impairment of essential metal handling. However, further studies aimed at assessment of the impact on Fe deficiency on metal metabolism are highly required.

Endothelial Dysfunction Induced by Cadmium and Mercury and its Relationship to Hypertension.

Hypertension is an important public health concern that affects millions globally, leading to a large number of morbidities and fatalities. The etiology of hypertension is complex and multifactorial, and it involves environmental factors, including heavy metals. Cadmium and mercury are toxic elements commonly found in the environment, contributing to hypertension. We aimed to assess the role of cadmium and mercury-induced endothelial dysfunction in the development of hypertension. A narrative review was carried out through database searches. In this review, we discussed the critical roles of cadmium and mercury in the etiology of hypertension and provided new insights into potential mechanisms of their effect, focusing primarily on endothelial dysfunction. Although the mechanisms by which cadmium and mercury induce hypertension have yet to be completely elucidated, evidence for both implicates impaired nitric oxide signaling in their hypertensive etiology.

Serum, Whole Blood, Hair, and Mucosal Essential Trace Element and Mineral Levels in Children with Verified Chronic Rhinosinusitis Undergoing Functional Endoscopic Sinus Surgery.

The objective of the present study was to assess hair, serum, whole blood, and excised tissue essential element content in children with chronic rhinosinusitis (CRS). Eighty-eight children with chronic rhinosinusitis and 66 healthy controls were enrolled in the present study. Evaluation of endoscopic Lund-Kennedy and computed tomography Lund-Mackay scores, as well as tissue sampling, was performed only in children with chronic rhinosinusitis. Assessment of Sino-Nasal Outcome Test-20 (SNOT-20) scores was performed in both cases and controls. Hair, whole blood, blood serum, and excised mucosal tissue (only in patients) analysis was performed using inductively coupled argon plasma mass-spectrometry. The obtained data demonstrate that whole blood Ca, Mg, Se, and Zn, as well as hair Ca, Cu, Mg, and Zn levels in the examined patients were significantly lower as compared with the control values. Only serum Zn concentration in children with CRS exceeded the respective control values, whereas serum Cu levels only tended to decrease in CRS. In turn, hair Fe content in children with CRS exceeded that in healthy controls. Regression analysis demonstrate that hair Ca levels, as well as whole blood Ca, Se, and Zn concentrations, were considered as negative predictors, whereas increased hair iron level was significantly directly associated with CRS. Significant associations between hair, serum, whole blood, and tissue element levels and Lund-Kennedy and Lund-Mackay scores were also revealed. Generally, the obtained data demonstrate that chronic rhinosinusitis is associated with impaired essential metal levels in pediatric patients with chronic rhinosinusitis. The observed alterations may contribute to CRS pathogenesis through modulation of mucociliary clearance, immunity, inflammatory response, and redox environment.