Original article: Low levels of selenium compounds are selectively toxic for a human neuron cell line through ROS/RNS increase and apoptotic process activation

Maraldi T, Riccio M, Zambonin L, Vinceti M, De Pol A, Hakim G.
Neurotoxicology. 2011 Mar;32(2):180-7. PMID: 21215776

Abstract

Organic and inorganic selenium compounds were used to examine whether low selenium concentration is able to trigger apoptotic degeneration in a human neuron cell line in vitro and to explore changes in reactive oxygen and nitrogen species and antioxidant protein content during the apoptotic processes. The results indicated that: (1) SKNBE neuroblastoma cells treated with sodium selenite, sodium selenate and seleno-methionine (0.1, 0.5 and 0.5 μM, respectively) for 24h exhibited a viability decrease, unlike kidney or prostatic cells; (2) the PARP (poly-ADP-ribose-polymerase) degradation and caspase activation detected by Western blot and flow cytometry fluorimetric examination showed induction of apoptosis; (3) during selenium treatment, a ROS/RNS increase occurred despite the GSH increment, as revealed by fluorimetric analysis; (4) the RNS production could be blocked by a peroxynitrite scavenger; (5) after exposure to selenium compounds, the concentration of nitric oxide synthase, manganese superoxide dismutase (SOD2), P-NF-kB (phospho nuclear factor kB), glutathione reductase and glutathione peroxidase increased, whereas that of P-ERK (phosphor extracellular signal-regulated kinase) decreased; (6) selenium presence induced copper/zinc superoxide dismutase (SOD1) translocation into mitochondria, in a way similar to what is observed in amyotrophic lateral sclerosis (ALS). This study supports epidemiologic studies showing the possibility that excess environmental exposure to Se represents a risk factor for a devastating human neurodegenerative disease.

Original article: The relation between amyotrophic lateral sclerosis and inorganic selenium in drinking water: a population-based case-control study

Vinceti M, Bonvicini F, Rothman KJ, Vescovi L, Wang F.
Environ Health. 2010 Dec 6;9:77. PMID: 21134276

Abstract

BACKGROUND: A community in northern Italy was previously reported to have an excess incidence of amyotrophic lateral sclerosis among residents exposed to high levels of inorganic selenium in their drinking water.
METHODS: To assess the extent to which such association persisted in the decade following its initial observation, we conducted a population-based case-control study encompassing forty-one newly-diagnosed cases of amyotrophic lateral sclerosis and eighty-two age- and sex-matched controls. We measured long-term intake of inorganic selenium along with other potentially neurotoxic trace elements.
RESULTS: We found that consumption of drinking water containing ≥ 1 μg/l of inorganic selenium was associated with a relative risk for amyotrophic lateral sclerosis of 5.4 (95% confidence interval 1.1-26) after adjustment for confounding factors. Greater amounts of cumulative inorganic selenium intake were associated with progressively increasing effects, with a relative risk of 2.1 (95% confidence interval 0.5-9.1) for intermediate levels of cumulative intake and 6.4 (95% confidence interval 1.3-31) for high intake.
CONCLUSION: Based on these results, coupled with other epidemiologic data and with findings from animal studies that show specific toxicity of the trace element on motor neurons, we hypothesize that dietary intake of inorganic selenium through drinking water increases the risk for amyotrophic lateral sclerosis.

Original article: Pooled analysis of recent studies on magnetic fields and childhood leukaemia

Kheifets L, Ahlbom A, Crespi CM, Draper G, Hagihara J, Lowenthal RM, Mezei G, Oksuzyan S, Schüz J, Swanson J, Tittarelli A, Vinceti M, Wunsch Filho V.
Br J Cancer. 2010 Sep 28;103(7):1128-35 PMID: 20877339

Abstract

BACKGROUND: Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We present a pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000.
METHODS: Seven studies with a total of 10,865 cases and 12,853 controls were included. The main analysis focused on 24-h magnetic field measurements or calculated fields in residences.
RESULTS: In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratios for exposure categories of 0.1-0.2 μT, 0.2-0.3 μT and ≥0.3 μT, compared with <0.1 μT, were 1.07 (95% CI 0.81-1.41), 1.16 (0.69-1.93) and 1.44 (0.88-2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat. An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model.
CONCLUSIONS: Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lack methodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fields and childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic.

Original article: A prospective study of dietary selenium intake and risk of type 2 diabetes

Stranges S, Sieri S, Vinceti M, Grioni S, Guallar E, Laclaustra M, Muti P, Berrino F, Krogh V.
BMC Public Health. 2010 Sep 21;10:564 PMID: 20858268

Abstract

BACKGROUND: Growing evidence raises concern about possible associations of high selenium exposure with diabetes in selenium-replete populations such as the US.In countries with lower selenium status, such as Italy, there is little epidemiological evidence on the association between selenium and diabetes. This study examined the prospective association between dietary selenium intake and risk of type 2 diabetes.
METHODS: The ORDET cohort study comprised a large sample of women from Northern Italy (n = 7,182). Incident type 2 diabetes was defined as a self-report of a physician diagnosis, use of antidiabetic medication, or a hospitalization discharge. Dietary selenium intake was measured by a semi-quantitative food-frequency questionnaire at the baseline examination (1987-1992). Participants were divided in quintiles based on their baseline dietary selenium intake.
RESULTS: Average selenium intake at baseline was 55.7 μg/day. After a median follow-up of 16 years, 253 women developed diabetes. In multivariate logistic regression analyses, the odds ratio for diabetes comparing the highest to the lowest quintile of selenium intake was 2.39, (95% CI: 1.32, 4.32; P for linear trend = 0.005). The odds ratio for diabetes associated with a 10 μg/d increase in selenium intake was 1.29 (95% CI: 1.10, 1.52).
CONCLUSIONS: In this population, increased dietary selenium intake was associated with an increased risk of type 2 diabetes. These findings raise additional concerns about the association of selenium intake above the Recommended Dietary Allowance (55 μg/day) with diabetes risk.