The role of cadmium in obesity and diabetes

Details

Published on Wednesday, 31 May 2017 12:00

Tinkov AA, Filippini T, Ajsuvakova OP, Aaseth J, Gluhcheva YG, Ivanova JM, Bjørklund G, Skalnaya MG, Gatiatulina ER, Popova EV, Nemereshina ON, Vinceti M, Skalny AV.

Sci Total Environ. 2017 May 31;601-602:741-755. doi: 10.1016/j.scitotenv.2017.05.224

Abstract

Multiple studies have shown an association between environmental exposure to hazardous chemicals including toxic metals and obesity, diabetes, and metabolic syndrome. At the same time, the existing data on the impact of cadmium exposure on obesity and diabetes are contradictory. Therefore, the aim of the present work was to review the impact of cadmium exposure and status on the risk and potential etiologic mechanisms of obesity and diabetes. In addition, since an effect of cadmium exposure on incidence of diabetes mellitus and insulin resistance was suggested by several epidemiologic studies, we carried out a meta-analysis of all studies assessing risk of prevalence and incidence of diabetes. By comparing the highest versus the lowest cadmium exposure category, we found a high risk of diabetes incidence (odds ratio=1.38, 95% confidence interval 1.12-1.71), which was higher for studies using urine as exposure assessment. On the converse, results of epidemiologic studies linking cadmium exposure and overweight or obesity are far less consistent and even conflicting, also depending on differences in exposure levels and the specific marker of exposure (blood, urine, hair, nails). In turn, laboratory studies demonstrated that cadmium adversely affects adipose tissue physiopathology through several mechanisms, thus contributing to increased insulin resistance and enhancing diabetes. However, intimate biological mechanisms linking Cd exposure with obesity and diabetes are still to be adequately investigated.

Elevated levels of selenium species in cerebrospinal fluid of amyotrophic lateral sclerosis patients with disease-associated gene mutations

Details

Published on Saturday, 06 May 2017 12:00

Mandrioli J, Michalke B, Solovyev N, Grill P, Violi F, Lunetta C, Conte A, Sansone VA, Sabatelli M, Vinceti M

Neurodegener Dis. 2017 May 6;17(4-5):171-180

Abstract

BACKGROUND: Although an increasing role of genetic susceptibility has been recognized, the role of environmental risk factors in amyotrophic lateral sclerosis (ALS) etiology is largely uncertain; among neurotoxic chemicals, epidemiological and biological plausibility has been provided for pesticides, the heavy metal lead, the metalloid selenium, and other persistent organic pollutants. Selenium involvement in ALS has been suggested on the basis of epidemiological studies, in vitro investigations, and veterinary studies in which selenium induced a selective toxicity against motor neurons.

OBJECTIVE: Hypothesizing a multistep pathogenic mechanism (genetic susceptibility and environmental exposure), we aimed to study selenium species in ALS patients carrying disease-associated gene mutations as compared to a series of hospital controls.

METHODS: Using advanced analytical techniques, we determined selenium species in cerebrospinal fluid sampled at diagnosis in 9 ALS patients carrying different gene mutations (C9ORF72, SOD1, FUS, TARDBP, ATXN2, and TUBA4A) compared to 42 controls.

RESULTS: In a patient with the tubulin-related TUBA4A mutation, we found highly elevated levels (in μg/L) of glutathione-peroxidase-bound selenium (32.8 vs. 1.0) as well as increased levels of selenoprotein-P-bound selenium (2.4 vs. 0.8), selenite (1.8 vs. 0.1), and selenate (0.9 vs. 0.1). In the remaining ALS patients, we detected elevated selenomethionine-bound selenium levels (0.38 vs. 0.06).

CONCLUSIONS: Selenium compounds can impair tubulin synthesis and the cytoskeleton structure, as do tubulin-related gene mutations. The elevated selenium species levels in the TUBA4A patient may have a genetic etiology and/or represent a pathogenic pathway through which this mutation favors disease onset, though unmeasured confounding cannot be excluded. The elevated selenomethionine levels in the other patients are also of interest due to the toxicity of this nonphysiological selenium species. Our study is the first to assess selenium exposure in genetic ALS, suggesting an interaction between this environmental factor and genetics in triggering disease onset.

Redox speciation of iron, manganese, and copper in cerebrospinal fluid by strong cation exchange chromatography - sector field inductively coupled plasma mass spectrometry

Details

Published on Monday, 17 April 2017 12:00

Solovyev N, Vinceti M, Grill P, Mandrioli J, Michalke B

Anal Chim Acta. 2017 Jun 22;973:25-33

Abstract

A new method of simultaneous redox speciation of iron (II/III), manganese (II/III), and copper (I/II) in cerebrospinal fluid (CSF) has been designed. For the separation of redox species strong cation exchange chromatography (SCX) with isocratic elution was employed. Species were detected using inductively coupled plasma sector field mass spectrometry (ICP-sf-MS), operating at medium resolution. The following parameters were optimized: analytical column, eluent composition and pH, CSF injection volume and dilution factor. Analytical column Dionex IonPac CS5A RFIC 4*250 mm was found to retain and separate species of interest the most effectively under the isocratic elution with a buffer, containing 50 mM ammonium citrate, 7.0 mM pyridine-2,6-dicarboxylic acid at pH = 4.2 and flow rate of 0.8 L min-1. Injection volume of 50 μL with CSF sample dilution of 1/3 (v/v) with the eluent was shown to result in minimal matrix suppression. For species identification, retention time matching with standards was used. The stability of metalloproteins (ferritin, transferrin, and ceruloplasmin) under elution conditions was evaluated. For the quantification of redox species, external calibration was employed. To avoid column contamination, a blank was run after measurement and all quantification values were blank subtracted. For recovery checks, species quantification data was verified against total content of an element, measured by dynamic reaction cell ICP-MS. Recoveries (sum of quantified species vs. total element determinations) were 82.5 ± 22% (Mn), 92 ± 11% (Fe), and 88.7 ± 12% (Cu). The method was tested using 38 real CSF samples. Limits of detection (3σ) for the CSF samples were 0.5 μg L-1, 0.6 μg L-1, and 0.8 μg L-1 for Fe, Mn, and Cu species, respectively. Retention time precision was 1-7.5% (as RSD), whereas peak area RSDs were in the range 5-11%, both depending on the species.

Toenail selenium as an indicator of environmental exposure: A cross-sectional study

Details

Published on Friday, 24 March 2017 12:00

Filippini T, Ferrari A, Michalke B, Grill P, Vescovi L, Salvia C, Malagoli C, Malavolti M, Sieri S, Krogh V, Bargellini A, Martino A, Ferrante M, Vinceti M.

Mol Med Rep. 2017 Mar 24;15(5):3405-3412

Abstract

The relation between toxicity and essentiality of selenium (Se) is of growing interest in human health, as the effects may widely differ depending of its different chemical species and the exposure levels. Toenail Se has been proposed as a reliable biomarker of long-term Se exposure, but few studies investigated the correlation between its toenail content and environmental determinants (i.e., dietary food intake). We aimed to determine the relation of toenail Se levels with serum Se species as well as food items. We recruited a random sample of Modena (Northern Italy) municipal residents, from whom we collected detailed personal information, dietary habits, toenail specimen for Se determination and a blood sample for serum Se speciation analysis. Toenail Se mean value was 0.96 µg/g (range, 0.47‑1.60), with slightly higher levels in females, in non-obese subjects and in Se supplements users, while it was lower in current smokers. Toenail Se positively correlated with organic Se forms, mainly selenoprotein P and selenocysteine, and inversely with the inorganic forms (selenite and selenate). Toenail Se was not associated with meat, cereals and dairy products consumption, positively correlated with fruit and slightly with vegetable intake, and negatively with fish and seafood consumption. Finally, no clear association emerged with estimated air Se exposure.

Determinants of serum manganese levels in an Italian population.

Details

Published on Friday, 24 March 2017 12:00

Filippini T, Michalke B, Grill P, Malagoli C, Malavolti M, Vescovi L, Sieri S, Krogh V, Cherubini A, Maffeis G, Lucchini R, Ferrante M, Vinceti M.

Mol Med Rep. 2017 Mar 24;15(5):3340-3349

Abstract

Manganese (Mn) is both essential and toxic for humans, mainly depending on the total levels and its species. Main sources of exposure include food and air pollution, particularly motorized traffic. We sought to determine the potential influence of these sources on serum total levels of Mn and Mn species. We selected a random sample of municipality residents from an Italian urban municipality, from whom we collected detailed personal information, dietary habits and a blood sample for serum Mn determination. We also assessed outdoor air Mn exposure, by modeling levels of particulate matter ≤10 µm (PM10) from motorized traffic at the residence of geocoded subjects. Serum Mn species generally showed higher levels in males and positive correlation with age, while no such differences were found according to smoking habits or use of dietary supplements. Among nutrients, only iron intake showed a relation with Mn [an inverse correlation with Mn‑ferritin (Mn‑Fer) and a direct one with inorganic‑Mn (Inorg‑Mn)]. Meat consumption directly correlated and fish and seafood inversely correlated with total Mn, Mn‑transferrin (Mn‑Tf) and Mn-citrate (Mn-Cit). Fruits and vegetables, including legumes and nuts, generally showed a positive correlation with all Mn species, especially Mn‑Cit, and an inverse one with Inorg‑Mn. Odds ratios (ORs) of having serum Mn levels above median value increased with increasing PM10 tertiles, with an OR for highest‑to‑lowest tertile of 7.40 (1.36‑40.25) in multivariate analysis. Analyses for Mn species did not highlight a clear comparable pattern. In conclusion, our results seem to demonstrate that PM10 exposure positively influences total Mn serum levels, while single Mn species show conflicting results.