Funkcije bubrega u rudara intermitentno izloženih parama elementarne žive

The authors investigated renal damage in 45 mercury miners under conditions of relatively short and low-level exposure to elemental (metallic) mercury vapour (Hg0). The analysis included urinary mercury, immunoelectrophoresis of urinary proteins, immunofixation and high-resolution electrophoresis, quantitative analysis of urinary albumin, and urinary a1-microglobulin before and after exposure. The activity of urinary N-acetyl-b- D-glucosaminidase (NAG) enzyme was determined after exposure. The average duration of exposure of miners was 37 (6–82) days. Urinary mercury significantly increased during exposure. Immunoelectrophoretic changes in the composition of urinary proteins occurred after exposure in 22 of 45 miners, of whom 15 showed high molecular weight (HMW) pattern of urinary proteins and seven showed low molecular weight (LMW) pattern. Only a slight increase in the urinary a1-microglobulin concentration and NAG activity was found in miners with the LMW pattern of urinary proteins. The results point to a slight glomerular and tubular damage in a significant proportion of exposed miners with increased absorption of mercury vapour.Pri profesionalnoj izloženosti parama elementarne žive (Hg0) mogu se pojaviti oštećenja bubrega. U ovom radu procjenjivana je mogućnost učinaka relativno kraće izloženosti nižim koncentracijama živinih para na glomerularnu i tubularnu funkciju bubrega. U 45 rudara su prije i nakon izloženosti određena živa i proteini u urinu. Nakon izloženosti određena je i aktivnost N-acetil-beta-D glukozaminidaze (NAG) u urinu. Proteini u urinu određeni su primjenom imunoelektroforeze, imunofiksacije i elektroforeze visoke rezolucije (velike sposobnosti razdvajanja), kao i pomoću kvantitativne analize albumina i alfa1-mikroglobulina. Rudari, inače, već duže intermitentno izloženi živinim parama, bili su u vrijeme istraživanja izloženi u prosjeku 37 (6–82) dana pri prosječnim koncentracijama 0,37 (0,05–0,73) mg/m3 zraka. Nakon izloženosti kod svih je rudara ustanovljena pojačana apsorpcija elementarne žive prosječnim koncentracijama žive u urinu 67,8±40,8 µg/g kreatinina. Imunoelektroforezom ustanovljene promjene u sastavu proteina u urinu nakon izloženosti su češće nego prije izloženosti (P<0,01). Kod tih rudara (u 22 od 45) s promjenama u sastavu proteina u urinu prevalencija uzoraka urina s proteinima velike molekularne mase veća je (15 od 45) nego prevalencija uzoraka urina s proteinima male molekularne mase (7 od 45). Nakon izloženosti koncentracije albumina u urinu nisu bile značajno povišene u odnosu na vrijednosti prije izloženosti. U podskupini rudara u čijim su urinima nađeni proteini male molekularne mase ustanovljen je blag porast alfa1- mikroglobulina (P=0,05). Živa u urinu nakon izloženosti u bila je u blagoj pozitivnoj korelaciji sa NAG u urinu (r=0,43; P<0,01). Prema ovim rezultatima moglo bi se zaključiti da je kod dijela promatranih osoba pojačana apsorpcija popraćena blagim – klinički neznačajnim – učincima na glomerularnu ili tubularnu funkciju bubrega. Promjene u sastavu proteina u urinu ustanovljene imunoelektroforetsim analizama, kvantitativne analize alfa1-mikroglobulina i NAG u urinu mogu se upotrijebiti kao biološki pokazatelj u zdravstvenom nadzoru radnika koji su intermitentno izloženi parama elementarne žive u niskim koncentracijama

Arsenic metabolites ; selenium ; and AS3MT, MTHFR, AQP4, AQP9, SELENOP, INMT and MT2A polymorphisms in Croatian-Slovenian population from PHIME-CROME study

The relationships between inorganic arsenic (iAs) metabolism, selenium (Se) status, and genetic polymorphisms of various genes, commonly studied in populations exposed to high levels of iAs from drinking water, were studied in a Croatian- Slovenian population from the wider PHIME-CROME project. Population consisted of 136 pregnant women in the 3rd trimester and 176 non-pregnant women with their children (n = 176, 8–9 years old). Their exposure to iAs, defined by As (speciation) analyses of biological samples, was low. The sums of biologically active metabolites (arsenite + arsenate + methylated As forms) for pregnant women, non-pregnant women, and children, respectively were: 3.23 (2.84–3.68), 1.83 (1.54– 2.16) and 2.18 (1.86–2.54) ng/mLSG ; GM (95 CI). Corresponding plasma Se levels were: 54.8 (52.8– 56.9), 82.3 (80.4–84.0) and 65.8 (64.3–67.3) ng/mL ; GM (95 CI). As methylation efficiency indexes confirmed the relationship between pregnancy/childhood and better methylation efficiency. Archived blood and/or saliva samples were used for single nucleotide polymorphism (SNP) genotyping of arsenic(3+) methyltransferase - AS3MT (rs7085104, rs3740400, rs3740393, rs3740390, rs11191439, rs10748835, rs1046778 and the corresponding AS3MT haplotype) ; methylene tetrahydrofolate reductase - MTHFR (rs1801131, rs1801133) ; aquaporin - AQP 4 and 9 (rs9951307 and rs2414539) ; selenoprotein P1 - SELENOP (rs7579, rs3877899) ; indolethylamine N- methyltransferase - INMT (rs6970396) ; and metallothionein 2A - MT2A (rs28366003). Associations of SNPs with As parameters and urine Se were determined through multiple regression analyses adjusted using appropriate confounders (blood As, plasma Se, ever smoking, etc.). SNPs’ influence on As methylation, defined particularly by the secondary methylation index (SMI), confirmed the ‘protective’ role of minor alleles of six AS3MT SNPs and their haplotype only among non-pregnant women. Among the other investigated genes, the carriers of AQP9 (rs2414539) were associated with more efficient As methylation and higher urine concentration of As and Se among non-pregnant women ; poorer methylation was observed for carriers of AQP4 (rs9951307) among pregnant women and SELENOP (rs7579) among non- pregnant women ; MT2A (rs28366003) was associated with higher urine concentration of AsIII regardless of the pregnancy status ; and INMT (rs6970396) was associated with higher As and Se concentration in non-pregnant women. Among confounders, the strongest influence was observed for plasma Se ; it reduced urine AsIII concentration during pregnancy and increased secondary methylation index among non-pregnant women. In the present study of populations with low As exposure, we observed a few new As–gene associations (particularly with AQPs). More reliable interpretations will be possible after their confirmation in larger populations with higher As exposure levels

Trace elements and APOE polymorphisms in pregnant women and their new-borns

We investigated the relationship between lipid binding glycoprotein apolipoprotein E (apoE; gene APOE) polymorphisms (ε4 allele carriers versus no carriers = ε4+/ε4-) and trace elements (TEs) (e.g., (methyl)mercury, arsenic, lead, cadmium, selenium, manganese, copper, and zinc) in mothers (N = 223) and their new-borns (N = 213) exposed to potentially toxic metal(loid)s from seafood consumption. The apoE isoform encoded by the ε4 allele is believed to have beneficial effects in early life but represents a risk factor for age-associated diseases. Under certain conditions ε4 carriers are more susceptible to oxidative stress and metal(loid) toxicity. DNA from Croatian pregnant women (N = 223, third trimester) and their new-borns (N = 176), was genotyped for APOE by TaqMan® SNP assay - rs429358 and rs7412. Seafood intake data and TE levels in maternal urine, milk, hair, peripheral venous blood, mixed cord blood, and new-borns' urine were available from previous studies. We compared TEs between ε4+ and ε4- carriers using Mann-Whitney U tests and applied multiple linear regression models to analyse the TE's dependence on the presence of allele ε4 (genotypes ε3/ε4, ε4/ε4) in combination with other explanatory variables. We identified 17% (n = 37) and 20% (n = 35) ε4 allele carriers in mothers and new-borns, respectively. The Mann-Whitney U test showed that mothers with the ε4 allele had significantly higher mean levels of (methyl)mercury in peripheral venous blood, cord blood, and hair; arsenic in urine and cord blood; and selenium in peripheral venous blood and plasma. However, taking confounders into account, only the maternal plasma selenium remained statistically significant in the linear regression models (ε4 carriers vs non-carriers: 62.6 vs 54.9 ng/mL, p < 0.001). Literature suggestions of possible ε4 allele impact on Hg levels were not observed, while superior selenium status observed in healthy pregnant women carrying allele ε4 could be linked to the proposed APOE ε4 beneficial effects early in life

Prenatal mercury exposure, neurodevelopment and apolipoprotein E genetic polymorphism

The aim of the present study was to evaluate the association between prenatal exposure to mercury (Hg) and neurodevelopment of the child, taking into account genetic polymorphism of apolipoprotein E (Apoe) and other relevant confounders. Six hundred and one mother-child pairs were recruited from the central Slovenia region and 243 from Rijeka, on the Croatian coast of the northern Adriatic. The total Hg in cord blood, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessment at 18 months of age and Apoe genotyping was performed on 361 children ; 237 of them were from Slovenia and 124 from Croatia. The results showed negative association between low- to-moderate Hg exposure in children with normal neurodevelopmental outcome and cognitive and fine motor scores at 18 months of age as assessed by BayleyIII. The Hg-related decrease in cognitive score was observed only in children carrying atleastone Apoe ε4 allele, while the decrease in fine motor scores was independent of the Apoe genotype. Adjusting for selenium (Se) and lead (Pb) levels, a positive association between Se and the language score and a negative association between Pb and the motor score was observed, but not in the subgroup of children carrying the ε4 allele