Cu isotope fractionation response to oxidative stress in a hepatic cell line studied using multi-collector ICP-mass spectrometry.

Reactive oxygen species (ROS) are generated in biological processes involving electron transfer reactions and can act in a beneficial or deleterious way. When intracellular ROS levels exceed the cell's anti-oxidant capacity, oxidative stress occurs. In this work, Cu isotope fractionation was evaluated in HepG2 cells under oxidative stress conditions attained in various ways. HepG2 is a well-characterised human hepatoblastoma cell line adapted to grow under high oxidative stress conditions. During a pre-incubation stage, cells were exposed to a non-toxic concentration of Cu for 24 h. Subsequently, the medium was replaced and cells were exposed to one of three different external stressors: H2O2, tumour necrosis factor α (TNFα) or UV radiation. The isotopic composition of the intracellular Cu was determined by multi-collector ICP-mass spectrometry to evaluate the isotope fractionation accompanying Cu fluxes between cells and culture medium. For half of these setups, the pre-incubation solution also contained N-acetyl-cysteine (NAC) as an anti-oxidant to evaluate its protective effect against oxidative stress via its influence on the extent of Cu isotope fractionation. Oxidative stress caused the intracellular Cu isotopic composition to be heavier compared to that in untreated control cells. The H2O2 and TNFα exposures rendered similar results, comparable to those obtained after mild UV exposure. The heaviest Cu isotopic composition was observed under the strongest oxidative conditions tested, i.e., when the cell surfaces were directly exposed to UV radiation without apical medium and in absence of NAC. NAC mitigated the extent of isotope fractionation in all cases.

Whole blood Fe isotopic signature in a sub-Saharan African population.

The Fe isotopic composition of an individual's whole blood has recently been shown to be an interesting clinical indicator of Fe status. The present study aimed to evaluate the influence of several endemic characteristics of a representative population of the South Kivu province, an Fe-rich volcanic African region, on the whole blood Fe isotopic composition. Both diabetes mellitus and the ferroportin Q248H mutation are very common in Africa and are strongly associated with impairments in Fe metabolism. Fe isotopic analysis of whole blood samples was carried out using multi-collector inductively coupled plasma-mass spectrometry (after chromatographic isolation of the target element). Forty-two male subjects (between 48 and 59 years old) living in Bukavu (South Kivu) were enrolled in this study. Among the selected population, wild-type subjects and subjects presenting the ferroportin Q248H mutation (heterozygotes and homozygotes) were included. Within each group, diabetic and non-diabetic patients were considered. The whole blood δ56Fe value ranged from -3.09‰ to -2.41‰. The δ56Fe value shows a significant negative correlation with the ferritin concentration. No correlation could be established between the whole blood δ56Fe value and the transferrin concentration, transferrin saturation or serum Fe concentration. The ferroportin Q248H mutation did not seem to have affected the whole blood Fe isotopic signature. The whole blood δ56Fe values were significantly higher in diabetic subjects than in non-diabetic subjects and showed a significant negative correlation with body mass index (BMI) values.

Determination of the total drug-related chlorine and bromine contents in human blood plasma using high performance liquid chromatography-tandem ICP-mass spectrometry (HPLC-ICP-MS/MS).

A fast, accurate and precise method for the separation and determination of the total contents of drug-related Cl and Br in human blood plasma, based on high performance liquid chromatography - inductively coupled plasma - tandem mass spectrometry (HPLC-ICP-MS/MS), has been developed. The novel approach was proved to be a suitable alternative to the presently used standard methodology (i.e. based on a radiolabelled version of the drug molecule and radiodetection), while eliminating the disadvantages of the latter. Interference-free determination of (35)Cl has been accomplished via ICP-MS/MS using H2 as reaction gas and monitoring the (35)ClH2(+) reaction product at mass-to-charge ratio of 37. Br could be measured "on mass" at a mass-to-charge of 79. HPLC was relied on for the separation of the drug-related entities from the substantial amount of inorganic Cl. The method developed was found to be sufficiently precise (repeatability <10% RSD) and accurate (recovery between 95 and 105%) and shows a linear dynamic range (R(2)>0.990) from the limit of quantification (0.05 and 0.01 mg/L for Cl and Br in blood plasma, respectively) to at least 5 and 1mg/L for Cl and Br, respectively. Quantification via either external or internal standard calibration provides reliable results for both elements. As a proof-of-concept, human blood plasma samples from a clinical study involving a newly developed Cl- and Br-containing active pharmaceutical ingredient were analysed and the total drug exposure was successfully described. Cross-validation was achieved by comparing the results obtained on Cl- and on Br-basis.

Hair minerals and metabolic health in Belgian elementary school girls.

Literature has repeatedly shown a relationship between hair minerals and metabolic health, although studies in children are currently lacking. This study aims to investigate hair levels of calcium (Ca), copper (Cu), magnesium (Mg), iron (Fe), phosphorus (P), and zinc (Zn) and their association with (1) overweight/obesity and (2) metabolic health in Flemish elementary school girls between 5 and 10 years old. Two hundred eighteen girls participated in this study as part of the baseline ChiBS project. Children were subjected to physical examinations, blood and hair sampling. Hair minerals were quantitatively determined via inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion. Body mass index (BMI) and body fat percentage (BF%) were studied as anthropometric parameters, and a metabolic score (including systolic and diastolic blood pressure, insulin resistance and non-high-density lipoprotein (non-HDL) cholesterol as parameters) was calculated, with higher scores indicating a more unhealthy metabolic profile. Hair Ca, Ca/Mg, and Ca/P positively correlated with the anthropometric parameters. An inverse correlation was observed between Ca, Mg, and Ca/P in hair and the metabolic score. Inverse correlations were also observed for individual metabolic parameters (i.e., diastolic blood pressure, homeostasis model assessment for insulin resistance, non-HDL cholesterol). In particular, girls with a total number of three or more metabolic parameters above the age-specific 75th percentile showed significantly reduced hair Ca, Mg, and Ca/P concentrations. This study showed reduced hair mineral concentrations in young girls with a more unhealthy metabolic profile. Positive associations were observed between some minerals and BMI and BF%.

Cross-sectional relationship between chronic stress and mineral concentrations in hair of elementary school girls.

Chronic stress exposure is associated with diverse negative health outcomes. It has been hypothesised that stress may also negatively affect the body's mineral status. This study investigates the association between chronic stress and long-term mineral concentrations of calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), phosphorus (P) and zinc (Zn) in scalp hair among elementary school girls. Complete information on child-reported stress estimates (Coddington Life Events Scale (CLES)), hair cortisone and hair mineral concentrations, and predefined confounders in the stress-mineral relationship (i.e. age, body mass index, physical activity, diet, hair colour and parental education) was provided cross-sectionally for 140 girls (5-10 years old). The relationship between childhood stress measures (predictor) and hair minerals (outcome) was studied using linear regression analysis, adjusted for the abovementioned confounders. Hair cortisone concentrations were inversely associated with hair mineral concentrations of Ca, Mg, Zn and the Ca/P ratio. Children at risk by life events (CLES) presented an elevated Ca/Mg ratio. These findings were persistent after adjustment for confounders. This study demonstrated an independent association between chronic stress measures and hair mineral levels in young girls, indicating the importance of physiological stress-mineral pathways independently from individual or behavioural factors. Findings need to be confirmed in a more heterogeneous population and on longitudinal basis. The precise mechanisms by which stress alters hair mineral levels should be further elucidated.

Mineral concentrations in hair of Belgian elementary school girls: reference values and relationship with food consumption frequencies.

Although evidence suggests that hair elements may reflect dietary habits and/or mineral intake, this topic remains controversial. This study therefore presents age-specific reference values for hair concentrations of Ca, Cu, Fe, Na, Mg, P and Zn using the LMS method of Cole, and investigates the relationship between dietary habits (i.e. food consumption frequencies) and hair mineral concentrations in 218 Belgian elementary school girls by reduced rank regression (RRR). Hair minerals were quantitatively determined via inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of 6-cm long vertex posterior hair samples. The Children's Eating Habits Questionnaire-Food Frequency Questionnaire was used to obtain information on food consumption frequency of 43 food items in the month preceding hair collection. The established reference ranges were in line with data for other childhood or adolescent populations. The retained RRR factors explained 40, 50, 45, 46, 44 and 48 % of the variation of Ca, Cu, Fe, Mg, P and Zn concentrations in hair, respectively. Although this study demonstrated that a large proportion of hair mineral variation may be influenced by food consumption frequencies in elementary school girls, a number of food groups known to be rich sources of minerals did not show a relation with certain hair minerals. Future research should focus on mechanisms and processes involved in mineral incorporation and accumulation in scalp hair, in order to fully understand the importance and influence of diet on hair minerals.