Selenoneine is a major selenium species in beluga skin and red blood cells of Inuit from Nunavik.

Nunavimmiut (Inuit of Nunavik, Northern Quebec, Canada) exhibit a high selenium (Se) status because of their frequent consumption of marine mammal foods. Indirect evidence from our previous studies had suggested that selenoneine - a novel selenocompound - may be accumulating in the blood of Nunavimmiut. We used a liquid-chromatography/inductively coupled tandem mass spectrometry (LC-ICP-MS/MS) method to measure concentrations of selenoneine and its methylated metabolite Se-methylselenoneine in archived red blood cells (RBC) obtained from 210 Nunavimmiut living in communities along the Hudson Strait, where marine mammal hunting and consumption are most frequent in Nunavik. This method was adapted to quantify selenoneine and its methylated metabolite in beluga mattaaq, an Inuit delicacy consisting of the skin with the underlying layer of fat and the major dietary source of Se for Nunavimmiut. Total selenium concentration was also measured in RBC and beluga mattaaq samples by isotope dilution ICP-MS/MS. The median selenoneine concentration in RBC was 413 µg Se/L (range = 3.20-3230 µg Se/L), representing 54% (median) of total Se content (range = 1.6-91%). Quantification of selenoneine in five beluga mattaaq samples (skin layer) from Nunavik revealed a median concentration of 1.8 µg Se/g wet wt (range = 1.2-7.4 µg Se/g), constituting 54% (median) of the total Se content (range = 44-74%). Se-methylselenoneine was also detected in Inuit RBC but not in beluga mattaaq, suggesting that selenoneine undergoes methylation in humans. Selenoneine may protect Nunavimmiut from methylmecury toxicity by increasing its demethylation in RBC and in turn decreasing its distribution to target organs.

Determinants of selenoneine concentration in red blood cells of Inuit from Nunavik (Northern Québec, Canada).

Selenium (Se) is a trace mineral essential to human health, and is especially abundant in marine foods consumed by Inuit populations in Nunavik (northern Quebec, Canada), leading to exceptionally high whole blood Se levels. While most epidemiological studies to date examine plasma or whole blood Se, little is known about the health implications of specific Se biomarkers (e.g. selenoproteins and small Se compounds). Selenoneine, a novel Se compound, is found in high concentrations in marine foods (and particularly beluga mattaaq) and the red blood cells (RBCs) of populations that consume them. We report here RBC selenoneine concentrations in a population of Inuit adults (n = 885) who participated in the Qanuippitaa? 2004 survey. Simple associations between RBC selenoneine and other Se and mercury (Hg) biomarkers were assessed using Spearman correlations and linear regressions. Wilcoxon ranksum tests were used to examine differences in biomarkers and characteristics between tertiles of RBC selenoneine concentration. A multiple linear regression analysis was used to determine factors (sociodemographic, lifestyle, and dietary) associated with RBC selenoneine concentrations. Selenoneine comprised a large proportion of whole blood Se and RBC Se in this population. Age and sex-adjusted geometric mean RBC selenoneine concentration was 118 µg/L (range: 1-3226 µg/L) and was much higher (p = 0.001) among women (150.3 µg/L) than men (87.6 µg/L) across all regions of Nunavik after controlling for age, region, and diet. RBC selenoneine was highly correlated with RBC Se (rs = 0.96, p < 0.001) and whole blood Se (rs = 0.89, p < 0.001), but only weakly correlated with plasma Se (rs = 0.13, p < 0.001). Overall, increasing age (standardized ß = 0.24), higher body-mass index (BMI; ß = 0.08), female sex (ß = 0.10), living in a Hudson Strait community (compared to Hudson Bay and Ungava Bay; ß = 0.38), and consuming beluga mattaaq (g/day; ß = 0.19) were positively associated with RBC selenoneine. Meanwhile, consumption of market meats (g/day; ß = -0.07) was negatively associated with RBC selenoneine. RBC selenoneine is an important biomarker of Se dietary intake from local marine foods in Inuit populations. Further studies are needed to examine the health effects of selenoneine intake and the underlying mechanisms for sex differences among Inuit populations.

Plasma levels of selenium-containing proteins in Inuit adults from Nunavik.

Selenium (Se) is highly abundant in marine foods traditionally consumed by Inuit of Nunavik (Northern Quebec, Canada) and accordingly, their Se intake is among the highest in the world. However, little is known regarding the biological implications of this high Se status in this Arctic indigenous population. We used a method combining affinity chromatography and inductively coupled plasma-mass spectrometry with quantification by post-column isotope dilution to determine total Se levels and concentrations of Se-containing proteins in archived plasma samples of Inuit adults who participated to the 2004 Nunavik Inuit Health Survey (N = 852). Amounts of mercury (Hg) associated with Se-containing proteins were also quantified. Results show that glutathione peroxidase 3 (GPx3), selenoprotein P (SelP) and selenoalbumin (SeAlb) represented respectively 25%, 52% and 23% of total plasma Se concentrations. In addition, small amounts of Hg co-eluted with each Se-containing protein and up to 50% of plasma Hg was associated to SelP. Total plasma Se concentrations (median = 139 µg L− 1; interquartile range (IQR) = 22.7 µg L− 1) were markedly lower and less variable than whole blood Se concentration (median = 261 µg L− 1, IQR = 166 µg L− 1). A non linear relation was observed between whole blood Se and plasma Se levels, with plasma Se concentrations leveling off at approximately 200 µg L− 1, whereas 16% and 3% of individuals exhibited whole blood concentrations higher than 500 µg L− 1 and 1000 µg L− 1, respectively. In contrast, a linear relationship was previously reported in communities consuming Brazil nuts which are rich Se, mainly present as selenomethionine. This suggests that a different selenocompound, possibly selenoneine, is present in the Arctic marine food chain and accumulates in the blood cellular fraction of Inuit.

Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in Eastern James Bay Cree adults.

There is growing evidence that cardiovascular health can be affected by exposure to methylmercury (MeHg), by a mechanism involving oxidative stress. Paraoxonase 1 (PON1) is a high-density lipoprotein-bound enzyme that hydrolyzes toxic oxidized lipids and protects against cardiovascular diseases. Evidence from in vitro studies indicates that MeHg can inhibit PON1 activity but little is known regarding this effect in humans. We investigated whether increased blood mercury levels are associated with decreased serum PON1 activity in Cree people who are exposed to MeHg by fish consumption. We conducted a multi-community study of 881 Cree adults living in Eastern James Bay communities (Canada). Multivariate analyses considered sociodemographic, anthropometric, clinical, dietary and lifestyle variables and six PON1 gene variants (rs705379 (-108C/T), rs662 (Q192R), rs854560 (L55M), rs854572 (-909C/G), rs854571 (-832C/T) and rs705381 (-162C/T)). In a multiple regression model adjusted for all potential confounding factors and the rs854560 PON1 variant, a statistically significant MeHg*rs705379 interaction was observed. Blood mercury levels were inversely associated with serum PON1 activities in individual homozygous for the -108T allele (P=0.009). Our results suggest a gene-environment interaction between the rs705379 polymorphism and MeHg exposure on PON1 activity levels in this aboriginal population. This finding will need to be replicated in other population studies.

Relation between methylmercury exposure and plasma paraoxonase activity in inuit adults from Nunavik.

BACKGROUND: Methylmercury (MeHg) exposure has been linked to an increased risk of coronary heart disease (CHD). Paraoxonase 1 (PON1), an enzyme located in the high-density-lipoprotein (HDL) fraction of blood lipids, may protect against CHD by metabolizing toxic oxidized lipids associated with low-density liproprotein and HDL. MeHg has been shown to inhibit PON1 activity in vitro, but this effect has not been studied in human populations. OBJECTIVES: This study was conducted to determine whether blood mercury levels are linked to decreased plasma PON1 activities in Inuit people who are highly exposed to MeHg through their seafood-based diet. METHODS: We measured plasma PON1 activity using a fluorogenic substrate and blood concentrations of mercury and selenium by inductively coupled plasma mass spectrometry in 896 Inuit adults. Sociodemographic, anthropometric, clinical, dietary, and lifestyle variables as well as PON1 gene variants (rs705379, rs662, rs854560) were considered as possible confounders or modifiers of the mercury-PON1 relation in multivariate analyses. RESULTS: In a multiple regression model adjusted for age, HDL cholesterol levels, omega-3 fatty acid content of erythrocyte membranes, and PON1 variants, blood mercury concentrations were inversely associated with PON1 activities [ß-coefficient = -0.063; 95% confidence interval (CI), -0.091 to -0.035; p < 0.001], whereas blood selenium concentrations were positively associated with PON1 activities (ß-coefficient = 0.067; 95% CI, 0.045-0.088; p < 0.001). We found no interaction between blood mercury levels and PON1 genotypes. CONCLUSIONS: Our results suggest that MeHg exposure exerts an inhibitory effect on PON1 activity, which seems to be offset by selenium intake.