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

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Published on Thursday, 31 March 2011 18:11

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.

Exposure to pesticides and risk of amyotrophic lateral sclerosis: a population-based case-control study

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Published on Friday, 31 December 2010 18:15

Bonvicini F, Marcello N, Mandrioli J, Pietrini V, Vinceti M.
Ann Ist Super Sanita. 2010;46(3):284-7. PMID: 20847462

Abstract

A few epidemiologic studies have suggested an association of agricultural work and pesticides exposure with a severe degenerative disease of the motor neurons, amyotrophic lateral sclerosis (ALS), though conflicting results have also been provided. We investigated through a population-based case-control study the possible relation between overall occupational exposure to pesticides and ALS risk in the northern Italy municipality of Reggio Emilia. By administering a questionnaire, we investigated occupational history and leisure-time habits of the 41 ALS patients diagnosed in the 1995-2006 period, and of 82 age- and sex-matched randomly sampled population controls. More cases than controls were found to have been exposed to pesticides for at least six months (31.7% vs 13.4%, respectively), in all cases within the occupational environment. In a conditional logistic regression model, we found an excess ALS risk associated with exposure to pesticides, with a relative risk of 3.6 (95% confidence interval 1.2-10.5). Such association persisted after inclusion in the statistical analysis of potential confounders. Despite the limited statistical stability of the risk estimates, these results appear to indicate that occupational exposure to pesticides is a risk factor for ALS, suggesting the need to further investigate this issue.

Possible involvement of overexposure to environmental selenium in the etiology of amyotrophic lateral sclerosis: a short review

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Published on Thursday, 30 December 2010 18:16

Vinceti M, Bonvicini F, Bergomi M, Malagoli C.
Ann Ist Super Sanita. 2010;46(3):279-83. PMID: 20847461

Abstract

Excess exposure to the metalloid selenium (Se), a trace element with both toxicological and nutritional properties, has been implicated in the etiology of a human motor neuron disease of unknown origin and extremely severe prognosis, sporadic amyotrophic lateral sclerosis (ALS). This relation has been suggested on the basis of two epidemiologic investigations which found an increased risk of ALS associated with residence in a seleniferous area or with consumption of drinking water with unusually high levels of inorganic hexavalent Se, in South Dakota and in northern Italy respectively. Biological plausibility to a Se-ALS relation is provided by veterinary medicine observations and toxicological studies, showing that Se, particularly the inorganic forms, has a selective toxicity to motor neurons in swine and in cattle. Neurotoxic effects of Se species have also been demonstrated in laboratory studies and, for the inorganic forms, even at very low concentrations. Selenium has also been shown to affect muscle function in experimental animal models. Overall, these findings from the epidemiologic and the toxicological literature indicate that environmental Se, particularly in its inorganic forms and at unexpectedly low levels of exposure, might be a risk factor for ALS, suggesting the opportunity to further investigate this issue.

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

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Published on Monday, 06 December 2010 18:12

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.

Pooled analysis of recent studies on magnetic fields and childhood leukaemia

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Published on Tuesday, 28 September 2010 18:13

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.

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