Increased Endocytosis of Cadmium-Metallothionein through the 24p3 Receptor in an In Vivo Model with Reduced Proximal Tubular Activity.

BACKGROUND: The proximal tubule (PT) is the major target of cadmium (Cd2+) nephrotoxicity. Current dogma postulates that Cd2+ complexed to metallothionein (MT) (CdMT) is taken up through receptor-mediated endocytosis (RME) via the PT receptor megalin:cubilin, which is the predominant pathway for reuptake of filtered proteins in the kidney. Nevertheless, there is evidence that the distal parts of the nephron are also sensitive to damage induced by Cd2+. In rodent kidneys, another receptor for protein endocytosis, the 24p3 receptor (24p3R), is exclusively expressed in the apical membranes of distal tubules (DT) and collecting ducts (CD). Cell culture studies have demonstrated that RME and toxicity of CdMT and other (metal ion)-protein complexes in DT and CD cells is mediated by 24p3R. In this study, we evaluated the uptake of labeled CdMT complex through 24p3R after acute kidney injury (AKI) induced by gentamicin (GM) administration that disrupts PT function. Subcutaneous administration of GM at 10 mg/kg/day for seven days did not alter the structural and functional integrity of the kidney's filtration barrier. However, because of PT injury, the concentration of the renal biomarker Kim-1 increased. When CdMT complex coupled to FITC was administered intravenously, both uptake of the CdMT complex and 24p3R expression in DT increased and also colocalized after PT injury induced by GM. Although megalin decreased in PT after GM administration, urinary protein excretion was not changed, which suggests that the increased levels of 24p3R in the distal nephron could be acting as a compensatory mechanism for protein uptake. Altogether, these results suggest that PT damage increases the uptake of the CdMT complex through 24p3R in DT (and possibly CD) and compensate for protein losses associated with AKI.

Natriuretic peptides and echocardiographic parameters in Mexican children environmentally exposed to arsenic.

BACKGROUND: Arsenic exposure is associated with cardiovascular risk in adults; however, few epidemiologic studies have evaluated biomarkers of cardiovascular risk in children who are environmentally exposed to arsenic. OBJECTIVE: The aim of this study was to assess the associations between urinary arsenic, plasma natriuretic peptides and echocardiographic parameters in Mexican children exposed to arsenic through the drinking water. METHODS: We conducted a cross-sectional study with 192 children (3-8 years old) from Zimapan, Hidalgo, Mexico. B-type natriuretic peptide (BNP), NT-proBNP and atrial natriuretic peptide (ANP) were measured by ELISA, urinary arsenic concentration (UAs) were measured via by hydride generation-cryotrapping-atomic absorption spectrometry, and cardiac parameters were measured by echocardiography. RESULTS: The median plasma concentrations of ANP, BNP and NT-proBNP were 36.9 ng/mL, 49.7 pg/mL, and 226.1 pg/mL, respectively. Using multivariable models, a dose-response relationship was observed between BNP concentrations and UAs tertiles (<47 ng/mL: reference, 47-72 ng/mL: 48.7 pg/mL, >72 ng/mL: 52.2 pg/mL, P-trend = 0.020). BNP concentrations also increased with increasing U-tAs as continuous variables (0.43 pg/mL increase per 1 ng/mL increase of U-tAs; P-Value = 0.008). Additionally, BNP was positively associated with arsenic methylated metabolites (U-MAs and U-DMAs). On the other hand, BNP was inversely related to relative wall thickness (RWT). No associations were found for other cardiac parameters. Finally, neither ANP nor NT-proBNP were significantly related to arsenic exposure or echocardiographic parameters. CONCLUSIONS: In this study, we showed associations between plasma BNP and arsenic exposure. Our results support the importance of reducing childhood arsenic exposure, which may have cardiovascular effects early in life.

Evaluation of vascular and kidney injury biomarkers in Mexican children exposed to inorganic fluoride.

Exposure to inorganic fluoride (F) has been implicated in cardiovascular and kidney dysfunction mainly in adult populations. However, limited epidemiological information from susceptible populations, such as children, is available. In this study we evaluated the relationship of F exposure with some vascular and kidney injury biomarkers in children. A cross-sectional study was conducted in 374 Mexican schoolchildren. Dental fluorosis and F concentrations in the water and urine were evaluated. The glomerular filtration rate (eGFR) and the urinary concentrations of kidney injury molecule 1 (KIM-1) and cystatin-C (uCys-C) were examined to assess kidney injury. The carotid intima media thickness (cIMT) and serum concentrations of vascular adhesion molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), endothelin 1(ET-1) and cystatin-C (sCys-C) were measured to assess vascular alterations. High proportions of children exposed to F were observed (79.7% above 1.2 ppm F in urine) even in the low water F exposure regions, which suggested additional sources of F exposure. In robust multiple linear regression models, urinary F was positively associated with eGFR (ß = 1.3, p = 0.015), uCys-C (ß = -8.5, p = 0.043), VCAM-1 (ß = 111.1, p = 0.019), ICAM-1 (ß = 57, p = 0.032) and cIMT (ß = 0.01, p = 0.032). An inverse association was observed with uCys-C (ß = -8.5, p = 0.043) and sCys-C (ß = -9.6, p = 0.021), and no significant associations with ET-1 (ß = 0.069, p = 0.074) and KIM-1 (ß = 29.1, p = 0.212) were found. Our findings revealed inconclusive results regarding F exposure and kidney injury. However, these results suggest that F exposure is related to early vascular alterations, which may increase the susceptibility of cardiovascular diseases in adult life.

Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the cumulus cell-oocyte complex.

In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC. Cumulus cell-oocyte complexes (COCs) isolated from mouse preovulatory follicles were cultured with 0, 0.22, 2.2, 22, 220, and 2200 nM BPA for 2 h. An additional 16-h incubation with epidermal growth factor (EGF) was performed to promote the occurrence of meiotic resumption and progression to metaphase II. Without EGF stimulus, BPA treatment increased the percentage of oocytes undergoing meiotic resumption, decreased GJIC in the COCs, and did not modify GJIC gene (Cx43 and Cx37) and protein (CX43) expression. Following EGF stimulus, BPA increased the percentage of oocytes that remained at the anaphase and telophase stages, and decreased the percentage of oocytes reaching the metaphase II stage. Concomitantly, BPA reduced the expansion of cumulus cells. Carbenoxolone (a GJIC inhibitor) and 6-diazo-5-oxo-l-norleucine (a cumulus cell-expansion inhibitor) exerted effects on meiotic division similar to those exerted by BPA. These data suggest that BPA accelerates meiotic progression, leading to impaired prophase I-to-metaphase II transition, and that this adverse effect is correlated with reduced bidirectional communication in the COC.

The shift in GH3 cell shape and cell motility is dependent on MLCK and ROCK.

Cytoskeletal organization, actin-myosin contractility and the cell membrane together regulate cell morphology in response to the cell environment, wherein the extracellular matrix (ECM) is an indispensable component. Plasticity in cell shape enables cells to adapt their migration mode to their surroundings. GH3 endocrine cells respond to different ECM proteins, acquiring different morphologies: a rounded on collagen I-III (C I-III) and an elongated on collagen IV (C IV). However, the identities of the molecules that participate in these responses remain unknown. Considering that actin-myosin contractility is crucial to maintaining cell shape, we analyzed the participation of MLCK and ROCK in the acquisition of cell shape, the generation of cellular tension and the cell motility mode. We found that a rounded shape with high cortical tension depends on MLCK and ROCK, whereas in cells with an elongated shape, MLCK is the primary protein responsible for cell spreading. Further, in cells with a slow and directionally persistent motility, MLCK predominates, while rapid and erratic movement is ROCK-dependent. This behavior also correlates with GTPase activation. Cells on C I-III exhibited higher Rho-GTPase activity than cells on C IV and vice versa with Rac-GTPase activity, showing a plastic response of GH3 cells to their environment, leading to the generation of different cytoskeleton and membrane organizations and resulting in two movement strategies, rounded and fibroblastoid-like.

Mercury levels in human population from a mining district in Western Colombia.

A biomonitoring study was carried out to examine the adverse impacts of total mercury in the blood (HgB), urine (HgU) and human scalp hair (HgH) on the residents of a mining district in Colombia. Representative biological samples (scalp hair, urine and blood) were collected from volunteered participants (n=63) to estimate the exposure levels of THg using a Direct mercury analyzer. The geometric mean of THg concentrations in the hair, urine and blood of males were 15.98µg/g, 23.89µg/L and 11.29µg/L respectively, whereas the females presented values of 8.55µg/g, 5.37µg/L and 8.80µg/L. Chronic urinary Hg (HgU) levels observed in male workers (32.53µg/L) are attributed to their long termed exposures to inorganic and metallic mercury from gold panning activities. On an average, the levels of THg are increasing from blood (10.05µg/L) to hair (12.27µg/g) to urine (14.63µg/L). Significant positive correlation was found between hair and blood urinary levels in both male and female individuals. Thus the present biomonitoring investigation to evaluate the Hg levels and associated health issues would positively form a framework for further developmental plans and policies in building an ecofriendly ecosystem.

Evaluation of kidney injury biomarkers in rat amniotic fluid after gestational exposure to cadmium.

Cadmium is a well-characterized nephrotoxic agent that is also capable of accumulating and diffusing across the placenta; however, only a few studies have addressed its effects over fetal kidneys and none of them has used a panel of sensitive and specific biomarkers for the detection of kidney injury. The goal of this study was to determine cadmium renal effects in rat fetuses by the quantification of early kidney injury biomarkers. Pregnant Wistar rats were exposed by inhalation to an isotonic saline solution or to CdCl2 solution (DDel =1.48 mg Cd kg(-1) day(-1) ) during gestational days (GD) 8-20. On GD 21, dams were euthanized and samples obtained. Kidney injury biomarkers were quantified in amniotic fluid samples and fetal kidneys were microscopically evaluated to search for histological alterations. Our results showed that cadmium exposure significantly raised albumin, osteopontin, vascular endothelial growth factor and tissue inhibitor of metalloproteinases-1 levels in amniotic fluid, whereas it decreased creatinine. Clusterin, calbindin and IFN-inducible protein 10 did not show any change. Accordingly, histological findings showed tubular damage and precipitations in the renal pelvis. In conclusion, gestational exposure to cadmium induces structural alterations in fetal renal tissue that can be detected by some kidney injury biomarkers in amniotic fluid samples. Copyright © 2016 John Wiley & Sons, Ltd.

Impaired endocytosis in proximal tubule from subchronic exposure to cadmium involves angiotensin II type 1 and cubilin receptors.

BACKGROUND: Chronic exposure to low cadmium (Cd) levels produces urinary excretion of low molecular weight proteins, which is considered the critical effect of Cd exposure. However, the mechanisms involved in Cd-induced proteinuria are not entirely clear. Therefore, the present study was designed to evaluate the possible role of megalin and cubilin (important endocytic receptors in proximal tubule cells) and angiotensin II type 1 (AT1) receptor on Cd-induced microalbuminuria. METHODS: Four groups of female Wistar rats were studied. Control (CT) group, vehicle-treated rats; LOS group, rats treated with losartan (an AT1 antagonist) from weeks 5 to 8 (10 mg/kg/day by gavage); Cd group, rats subchronically exposed to Cd (3 mg/kg/day by gavage) during 8 weeks, and Cd + LOS group, rats treated with Cd for 8 weeks and LOS from weeks 5-8. Kidney Cd content, glomerular function (evaluated by creatinine clearance and plasma creatinine), kidney injury and tubular function (evaluated by Kim-1 expression, urinary excretion of N-acetyl-ß-D-glucosaminidase (NAG) and glucose, and microalbuminuria), oxidative stress (measured by lipid peroxidation and NAD(P)H oxidase activity), mRNA levels of megalin, expressions of megalin and cubilin (by confocal microscopy) and AT1 receptor (by Western blot), were measured in the different experimental groups. Data were analyzed by one-way ANOVA or Kruskal-Wallis test using GraphPad Prism 5 software (Version 5.00). P < 0.05 was considered statistically significant. RESULTS: Administration of Cd (Cd and Cd + LOS groups) increased renal Cd content. LOS-treatment decreased Cd-induced microalbuminuria without changes in: plasma creatinine, creatinine clearance, urinary NAG and glucose, oxidative stress, mRNA levels of megalin and cubilin, neither protein expression of megalin nor AT1 receptor, in the different experimental groups studied. However, Cd exposure did induce the expression of the tubular injury marker Kim-1 and decreased cubilin protein levels in proximal tubule cells whereas LOS-treatment restored cubilin levels and suppressed Kim-1 expression. CONCLUSION: LOS treatment decreased microalbuminuria induced by Cd apparently through a cubilin receptor-dependent mechanism but independent of megalin.

How to stay together? Habitat use by three sympatric sharks in the western coast of Baja California Sur, Mexico.

Sharks are top predators and play an important role in the regulation of marine ecosystems at lower trophic position. Mustelus californicus, Sphyrna zygaena, and Isurus oxyrinchus prove to be important fishery resources along the western coast of Baja California Sur and cohabit the same coastal areas, probably sharing resources. However, our knowledge about ecological dynamics of multiple species coexisting and sharing similar habitat resources is still limited, particularly for predators such as sharks. Therefore, this study focuses on the analysis of trophic ecology of the sharks species, using carbon (13C) and nitrogen (15N) stable isotope values in muscle tissues coupled with trace element concentration (Hg, Se, and Cd) in muscle and hepatic tissues of sharks. The values of δ13C (M. californicus -17.3 ± 1.1‰, S. zygaena -17.9 ± 0.5‰, and I. oxyrinchus -18.3 ± 0.3‰) and δ15N (M. californicus 18.2 ± 1.1‰, S. zygaena 18.4 ± 0.9‰, and I. oxyrinchus 17.8 ± 1.1‰) indicated that these species feed in the Gulf of Ulloa all throughout the year, and for extended periods with similar habitat use and trophic niche. The above-mentioned statement is also a conclusion supported by the significant correlation between isotopic and trace element concentrations in the muscular tissues in all studied species. Thus, the results of the present study emphasize the habitat and niche characteristics of three sympatric sharks off the coast of Baja California Sur, Mexico.

Mercury, selenium and cadmium in juvenile blue (Prionace glauca) and smooth hammerhead (Sphyrna zygaena) sharks from the Northwest Mexican Pacific coast.

Cadmium, selenium, and mercury concentrations were measured in muscle and liver of juvenile blue (Prionace glauca) and smooth hammerhead (Sphyrna zygaena) sharks caught on the west coast of Baja California Sur, Mexico, to evaluate the human health risk associated with its consumption. Cd and Hg were lower than the maximum allowable limit for human consumption established by the Mexican government (Hg = 1.0 µg g-1 and Cd = 0.50 µg g-1). Interspecific differences in trace elements accumulation denoted diet variations and physiological requirements of each shark species. Calculated biomagnification factor (BMF) values confirmed a prey-predator trophic transfer of elements. Not significant results of Selenium health benefit Index value (P. glauca = -0.46; S. zygaena = -0.02) signify no potential risks for human health. However, calculated Hazard Index values displayed possible health hazards to the children who consume blue shark meat regularly. The local population is advised regarding the ingestion rates of shark.

Mercury and selenium concentrations in different tissues of brown smooth-hound shark (Mustelus henlei) from the western coast of Baja California Sur, Mexico.

A study on mercury (Hg) and selenium (Se) concentrations in the liver and muscle of brown smooth-hound shark Mustelus henlei and its principal prey items, was conducted in the western coast of Baja California Sur, Mexico. Average Hg concentrations were found to be high in the muscle than in the liver; however, Hg concentrations were below the maximum permissible limits, and hence, the consumption of this species does not constitute a risk to human health. The mean Se concentrations were higher in the liver than in the muscle. The results of Hg: Se molar ratio revealed that Se counteracts the toxicity of Hg in hepatic tissues, whereas the contrary occurs in the muscle. Significant differences in Hg and Se accumulation were observed between females and males. Biomagnification factor values >1 demonstrate a biomagnification process from its principal prey species (i.e., red crab, Pleuroncodes planipes and Pacific mackerel, Scomber japonicus).

Mercury-selenium concentrations in silky sharks (Carcharhinus falciformis) and their toxicological concerns in the southern Mexican Pacific.

Mercury- Selenium concentrations were determined in 136 samples of Carcharhinus falciformis (Silky shark) sampled from the Chiapas coast, Gulf of Tehuantepec, Mexico during August 2014 - January 2015. Average Hg concentrations in neonates and juveniles (all values in µg g-1 w.w.) were found to be 0.115 and 0.129 respectively, below the maximum permissible limit of 1 µg g-1 set by the Mexican government. However, excess Se values (all values in µg g-1 d.w.) observed in neonates (5.366) and juveniles (2.815) prove to maintain antioxidant ability by inducing Hg excretion and reducing its toxicity. Calculated Biomagnification Factor (BMFTL) denoted high values for the prey C.hippurus, signifying absolute magnification of Hg and Se along the food chain. This study provides key toxicological evidences of Hg- Se interaction and their effects in marine systems and human health.

Bioaccumulation and trophic transfer of potentially toxic elements in the pelagic thresher shark Alopias pelagicus in Baja California Sur, Mexico.

Pelagic thresher shark (Alopias pelagicus) is a circumglobal species with high ecological and economic importance. Concentrations of mercury, selenium and cadmium in the muscle and liver tissues of A. pelagicus captured from Baja California Sur, Mexico were determined for assessing the potential human hazard. Results revealed that the average concentrations of Hg (0.76 mg kg-1) and Cd (0.18 mg kg-1) in muscle tissues were below the maximum permissible limits for human consumption. Se in the muscles were relatively low (mean: 0.30 mg kg-1 -1) resulting in a molar excess of Hg over Se. Average levels of hepatic Cd were extremely higher than the maximum limit for consumption. Organotropism of Hg was muscle > liver, whereas Se and Cd presented an order of liver > muscle. Biomagnification Factor (BMF) emphasized the trophic transfer of elements. Selenium Health Benefit value was negative (-3.76) posing potential health risks demanding regular monitoring for health risks.

Bioaccumulation and trophic transfer of Cd in commercially sought brown smoothhound Mustelus henlei in the western coast of Baja California Sur, Mexico.

A study on cadmium concentration in Mustelus henlei (liver and muscle) was carried out in an area influenced by natural phosphorite deposits and coastal upwelling. Our results indicate that liver (0.96 µg/g) concentrations were higher compared to the muscle (0.040 µg/g) suggesting it is on the safer level for human consumption. The male/female ratio indicates higher values (based on liver & muscle) in males (0.899 µg/g), which contributes to these differences in concentration. Higher values in the liver (0.96 µg/g) is due to the influence of phosphorite deposits in the region as well as the high metabolic activity. The other important factor responsible for these high Cd values are the prey, which also poses high values and is well supported by the biomagnification (1.08 & 4.57) of this element. The study also benefited in evaluating the environmental conditions for this particular species and elemental concentration in relation to human health.

Alpha-tocopherol protects against the renal damage caused by potassium dichromate.

Exposure to hexavalent chromium (Cr(6+)) causes mutagenic, carcinogenic, and toxic effects, some of which have been associated with its oxidative capacity. In the kidney, Cr(6+) has been claimed to provoke necrosis of the proximal tubular cells. Our aim was to assess the functional involvement of the different segments that form the nephron in a model of acute renal failure caused by potassium dichromate and the participation of oxidative damage in this process. We also studied the possible protective effect of alpha-tocopherol (alpha-TOC) against renal damage. Wistar female rats 200g body weight (bw) received potassium dichromate (15mg/kg, sc, single dose). Lipid peroxidation and renal function were evaluated on days 0, 1, 2, 3, 7, 10, and 14. A second group received alpha-TOC (125mg/kg, by gavage) 5 days before and during dichromate exposure (same dose as for the first group), and was monitored at 0, 2, and 7 days of exposure. Creatinine clearance, glucose and sodium fractional excretions, p-aminohippurate uptake, free-water and osmolal clearances were also measured. Thiobarbituric acid-reactive substances were quantified in renal cortex. The results revealed altered proximal tubule function, decreased glomerular filtration, and distal segment dysfunction, accompanied by oxidative damage 48h after exposure to dichromate. In the alpha-TOC-treated group proximal reabsorptive and secretory functions were preserved, suggesting that oxidative damage is a participating mechanism in dichromate toxicity on these functions. In contrast alpha-TOC did not prevent glomerular or distal dysfunction, indicating selectivity of the protection afforded by this compound on the toxicity of dichromate, at the several components of the nephron.

Cadmium concentration in liver and muscle of silky shark (Carcharhinus falciformis) in the tip of Baja California south, México.

Cadmium concentrations were determined in the tissues of muscle and liver of Carcharhinus falciformis (silky shark) sampled in Todos Santos, Baja California South, Mexico. This is one of the main shark species for human consumption in Mexico. Results indicate that accumulation of Cd varied in both sexes, based on its metabolism, sex, maturity and other biological characteristics. High Cd values were observed in the liver of adults of male (529.61µgg(-1)) and female (457.43µgg(-1)), whereas, in muscular tissues it was low (0.37µgg(-1)) than the prescribed permissible limits for seafood (0.5µgg(-1)). Substantial correlations were observed between body length and Cd values in adults except young male due to faster growth rate and its metabolism. The study indicated the impact of environmental conditions in the accumulation of Cd and its risk to the food web structure in the marine environment and health hazard for humans.

The nephroprotection exerted by curcumin in maleate-induced renal damage is associated with decreased mitochondrial fission and autophagy.

We have previously reported that the antioxidant curcumin exerts nephroprotection in maleate-induced renal damage, a model associated with oxidative stress. However, the mechanisms involved in curcumin protective effect were not explored, to assess this issue, curcumin was administered daily by gavage (150 mg/kg) five days before a single maleate (400 mg/kg)-injection. Curcumin prevented maleate-induced proteinuria, increased heat shock protein of 72 KDa (Hsp72) expression, and decreased plasma glutathione peroxidase activity. Maleate-induced oxidative stress by increasing the nicotinamide-adenine dinucleotide phosphate oxidase 4 (NOX4) and mitochondrial complex I-dependent superoxide anion (O2 •- ) production, formation of malondialdehyde (MDA)- and 3-nitrotyrosine (3-NT)-protein adducts and protein carbonylation and decreased GSH/GSSG ratio. Curcumin treatment ameliorated all the above-described changes. The maleate-induced epithelial damage, evaluated by claudin-2 and occludin expressions, was ameliorated by curcumin. It was found that maleate-induced oxidative stress promoted mitochondrial fission, evaluated by dynamin-related protein (Drp) 1 and fission (Fis) 1 expressions and by electron-microscopy, and autophagy, evaluated by phospho-threonine 389 from p70 ribosomal protein S6 kinase (p-Thr 389 p70S6K), beclin 1, microtubule-associated protein 1A/1B-light chain 3 phosphatidylethanolamine conjugate (LC3-II), autophagy-related gene 5 and 12 (Atg5-Atg12) complex, p62, and lysosomal-associated membrane protein (LAMP)-2 expressions in isolated proximal tubules and by electron-microscopy and LC-3 immunolabelling. Curcumin treatment ameliorated these changes. Moreover, curcumin alone induced autophagy in proximal tubules. These data suggest that the nephroprotective effect exerted by curcumin in maleate-induced renal damage is associated with decreased mitochondrial fission and autophagy. © 2016 BioFactors, 42(6):686-702, 2016.

Blood pressure, left ventricular geometry, and systolic function in children exposed to inorganic arsenic.

BACKGROUND: Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few epidemiological studies have been focused on iAs exposure-related cardiovascular disease in children. OBJECTIVE: In this study we investigated the association between iAs exposure, blood pressure (BP), and functional and anatomical echocardiographic parameters in children. METHODS: A cross-sectional study of 161 children between 3 and 8 years was conducted in Central Mexico. The total concentration of arsenic (As) species in urine (U-tAs) was determined by hydride generation-cryotrapping-atomic absorption spectrometry and lifetime iAs exposure was estimated by multiplying As concentrations measured in drinking water by the duration of water consumption in years (LAsE). BP was measured by standard protocols, and M-mode echocardiographic parameters were determined by ultrasonography. RESULTS: U-tAs concentration and LAsE were significantly associated with diastolic (DBP) and systolic blood pressure (SBP) in multivariable linear regression models: DBP and SBP were 0.013 (95% CI: 0.002, 0.024) and 0.021 (95% CI: 0.004, 0.037) mmHg higher in association with each 1-ng/mL increase in U-tAs (p < 0.025), respectively. Left ventricular mass (LVM) was significantly associated with LAsE [5.5 g higher (95% CI: 0.65, 10.26) in children with LAsE > 620 compared with < 382 µg/L-year; p = 0.03] in an adjusted multivariable model. The systolic function parameters left ventricular ejection fraction (EF) and shortening fraction were 3.67% (95% CI: -7.14, -0.20) and 3.41% (95% CI: -6.44, -0.37) lower, respectively, in children with U-tAs > 70 ng/mL compared with < 35 ng/mL. CONCLUSION: Early-life exposure to iAs was significantly associated with higher BP and LVM and with lower EF in our study population of Mexican children.

Effects of acute sodium fluoride exposure on kidney function, water homeostasis, and renal handling of calcium and inorganic phosphate.

Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver and kidney. In this study, we performed an early analysis of renal function using a clearance technique in Wistar rats acutely exposed to fluoride at a plasma concentration of 0.625 µg/ml. Our results revealed that fluoride, at a concentration close to the concentration present in the serum after environmental exposure, induced a significant tubular dysfunction, resulting in diluted urine, impaired protein reabsorption, and increased calcium and phosphate urinary excretion. Our work demonstrates that even acute exposures to low concentrations of NaF may induce renal damage and confirms that, after exposure, the kidney participates directly in the calcium and phosphate deficiencies observed in fluoride-exposed populations.