Toxic metals are extensively found in the environment, households, and workplaces and contaminate food and drinking water. The crosstalk between environmental exposure to toxic metals and human ...diseases has been frequently described. The toxic mechanism of action was classically viewed as the ability to dysregulate the redox status, production of inflammatory mediators and alteration of mitochondrial function. Recently, growing evidence showed that heavy metals might exert their toxicity through microRNAs (miRNA)-short, single-stranded, noncoding molecules that function as positive/negative regulators of gene expression. Aberrant alteration of the endogenous miRNA has been directly implicated in various pathophysiological conditions and signaling pathways, consequently leading to different types of cancer and human diseases. Additionally, the gene-regulatory capacity of miRNAs is particularly valuable in the brain-a complex organ with neurons demonstrating a significant ability to adapt following environmental stimuli. Accordingly, dysregulated miRNAs identified in patients suffering from neurological diseases might serve as biomarkers for the earlier diagnosis and monitoring of disease progression. This review will greatly emphasize the effect of the toxic metals on human miRNA activities and how this contributes to progression of diseases such as cancer and neurodegenerative disorders (NDDs).
An integrated study on the levels of 7 polybrominated diphenyl ethers (PBDEs) in house dust and breast milk samples from women (N = 30) living in these households was conducted.
∑PBDEs ranged from ...<LOD to 523ngg-1 dust (median 4.9ngg-1 dust), and from 0.16 to 6.3ngg-1 lipid weight (lw) (median 0.49ngg-1 lw), in house dust and breast milk samples, respectively. Statistically significant correlations were observed between the mass fractions of BDE-153 from breast milk, and BDE-47, BDE-99 and BDE-100 from house dust, congeners that all originate from the “penta” formulation, indicating its dominance as PBDE exposure source in the examined household dusts. The number of electronic and electrical devices, and age of the building were positive, and the number of upholstered furniture and household area were negative predictors of PBDE dust levels. Mothers age was negative predictor of the PBDE levels in breast milk, possibly due to dilution of PBDEs in total body fat accumulated over the years. The results of health risk assessment suggest that detected PBDE levels don’t pose non-cancer risk to the study population.
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•Seven PBDEs were determined in matched (N=30) household dust and breast milk samples•Statistical analysis revealed household parameters that correlate with PBDE levels•Mothers age is negative predictor of PBDE levels in breast milk•Mothers were most exposed to the “penta” formulation in their households
The decline of male fertility has become a serious public health concern over the last decades, coinciding with an increase in environmental exposure to toxic pollutants. Toxic elements cadmium (Cd), ...arsenic (As), and lead (Pb) seem to contribute to declining fertility in men through progressive impairment of semen quality. Reproductive toxicity of these elements is mediated by multiple mechanisms. Although experimental animal studies generally support an adverse role of Cd, As, and Pb in human reproduction issues, data on the effects induced by the levels of toxic elements that represent environmental exposure are inconsistent. This review summarizes reports from experimental studies in animals and epidemiological observational findings from environmental exposure to Cd, As, and Pb, with special focus on semen quality parameters as the indicator of male fertility.
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•Cd, As, and Pb are important reproductive toxicants.•Toxicity mechanisms include oxidative stress, apoptosis, inflammation, and endocrine disruption.•Low-level exposure to Cd, As, and/or Pb may impair semen quality parameters in men.•Additional epidemiological studies including general population are recommended.
The present study reports for the first time the levels of 7 polybrominated diphenyl ether (PBDE) congeners and 11 polycyclic aromatic hydrocarbons (PAH) measured in dust samples collected in 10 ...kindergartens, 11 workplaces, and 25 cars from Zagreb, Croatia. ΣPBDEs mass fractions were 3.11–14.42, <LOD‐313.75, and 0.6–5666.98 ng g−1 dust, while ΣPAHs were 244.9–833.0, 230.5–5632.7, and 395.6–12114.8 ng g−1 dust in kindergartens, workplaces, and cars, respectively. In the central case scenario, dust from homes contributed to the intake of PBDEs and PAHs the most, while for PBDEs in the worst‐case scenario, the intake through car dust prevailed. Carcinogenic and non‐carcinogenic risks were assessed for PAHs and PBDEs, respectively, for two age groups (adults and toddlers) and for professional drivers as a specific group. The hazard index for adults, toddlers, and professional drivers for PBDEs was less than 1 indicating that there is no significant risk of non‐carcinogenic effects due to exposure to these chemicals. Total carcinogenic risk for PAHs was negligible for all groups in the central case scenario, but the Incremental Lifetime Cancer Risk values >10−6 in the worst‐case scenario indicated a potential risk, especially for professional drivers. Also, in the cases of elevated contaminant levels, toddlers are susceptible to a higher risk, despite the short time they spend in cars.
Indoor dust presents an important source of daily exposure to toxic elements. The present study reports for the first time the levels of Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, Sn, Se, Sr, ...Tl, V, and Zn measured in dust samples collected from 10 kindergartens and 21 cars from Zagreb, Croatia. Based on the obtained data, we assessed the health risks from overall daily exposure to trace elements for children aged 2–6 years taking into account three pathways of dust intake—ingestion, dermal absorption, and inhalation. The median concentration of most elements was significantly higher in dust obtained from cars compared to kindergartens, especially in the cases of Co (11.62 vs. 3.60 mg kg−1), Cr (73.55 vs. 39.89 mg kg−1), Cu (186.33 vs. 26.01 mg kg−1), Mo (8.599 vs. 0.559 mg kg−1), Ni (37.05 vs. 17.38 mg kg−1), and Sn (9.238 vs. 1.159 mg kg−1). Oral intake was identified as the most important exposure pathway, except for Cr, Ni, and Sb where dermal contact was the main route of exposure. Health risk assessment indicated that no adverse effects are expected from overall exposure to trace elements. Although the cases of high exposure to toxic elements are not common in areas with no significant environmental pollutants, due to the health threat they may present even at low levels, their status should be carefully monitored.
Given the large amount of time people spend indoors today, human exposure to indoor contaminants causes increasing public health concerns. The present study reports for the first time the levels of 7 ...polybrominated diphenyl ether (PBDE) congeners, and 18 trace elements measured in dust samples collected in 68 households from Zagreb, Croatia. Based on the obtained data from dust analysis and the questionnaire on the house characteristics and habits of the residents, we aimed to assess the possible indoor sources of PBDEs/elements, and the associated health risks.
Mass concentrations of ΣPBDE ranged from 0.16 and 200.09 ng g−1 dust (median 4.19 ng g−1 dust). The most frequently detected congeners were BDE-99 and BDE-183 found in >88% of samples, while for trace elements, Al, Fe, Zn, Mn and Cu were found at the highest concentrations (enumerated in the descending order). The regression analysis indicated that renovation, number of residents and hours spent using electronic devices are significant predictors for determining PBDE dust concentrations, while the house age, and the house area were identified as the most important contributors for most trace elements. Our health risk assessment considering dust ingestion and dermal absorption of analyzed dust indicated that no adverse health effects are expected in toddlers and adults from exposure to PBDEs or trace elements in house dust. However, calculating the worst case exposure scenario based on the maximum measured concentrations and high dust intake rates, it was estimated that there is a risk of potential adverse health effects for Co (HI > 1). Even though the cases of high exposure to toxic elements from dust are sporadic, and not common among the general population, this exposure scenario should be included whenever assessing the background exposure of children.
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•Levels of 7 PBDEs and 18 trace elements were measured in indoor dust from 68 households.•Linear regression defined the household factors that correlate with PBDE/element levels.•Exposure to PBDEs from house dust does not present health risk to residents.•In cases of high exposure, Co from dust may pose non-carcinogenic risk to toddlers.
Nanotechnology has the potential to provide formulations of antitumor agents with increased selectivity towards cancer tissue thereby decreasing systemic toxicity. This
study evaluated the potential ...of novel nanoformulation based on poly(lactic-
-glycolic acid) (PLGA) to reduce the cardiotoxic potential of doxorubicin (DOX).
toxicity of PLGADOX was compared with clinically approved non-PEGylated, liposomal nanoformulation of DOX (LipoDOX) and conventional DOX form (ConvDOX). The study was performed using Wistar Han rats of both sexes that were treated intravenously for 28 days with 5 doses of tested substances at intervals of 5 days. Histopathological analyses of heart tissues showed the presence of myofiber necrosis, degeneration processes, myocytolysis, and hemorrhage after treatment with ConvDOX, whereas only myofiber degeneration and hemorrhage were present after the treatment with nanoformulations. All DOX formulations caused an increase in the troponin T with the greatest increase caused by convDOX. qPCR analyses revealed an increase in the expression of inflammatory markers IL-6 and IL-8 after ConvDOX and an increase in IL-8 expression after lipoDOX treatments. The mass spectra imaging (MSI) of heart tissue indicates numerous metabolic and lipidomic changes caused by ConvDOX, while less severe cardiac damages were found after treatment with nanoformulations. In the case of LipoDOX, autophagy and apoptosis were still detectable, whereas PLGADOX induced only detectable mitochondrial toxicity. Cardiotoxic effects were frequently sex-related with the greater risk of cardiotoxicity observed mostly in male rats.
Chronic exposure to high inorganic As levels in drinking water has been related to many diseases, including type 2 diabetes mellitus (T2D). The association with low and moderate As levels, however, ...remains controversial and has yet not been studied in European populations.
This study aimed to investigate possible association between As exposure and biomarkers of T2D in Croatian population. Observation recruited 86 adults from Eastern Croatia, where groundwater is contaminated with inorganic As, and 116 adults from Western Croatia, where As levels in drinking water are low. Both populations were divided in patient groups (T2D or prediabetes) and healthy controls. Exposure was assessed by determining total As in blood and urine and As metabolites in urine.
Eastern Croatian population had a significantly higher content of As in urine than Western, whereas the opposite was true for arsenobetain. Total As and As metabolites in urine positively correlated with hemoglobin A1c (HbA1c) and negatively with albuminuria.
This study provides important preliminary data on the levels of As in urine and blood and their association with biomarkers of T2D in Croatian population exposed to low or moderate levels of As through drinking water as a solid basis for further research of the pathophysiological effects of such As exposure on the status and complications of diabetes.
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•This is first study providing data on urinary levels of As species in Croatian population.•Correlation between As in urine and blood with biomarkers of diabetes were investigated.•Higher concentrations of As species in urine were associated with geographical origin.•As levels in urine positively correlated with HbA1c and negatively with albuminuria
Although considered a good alternative to organophosphate pesticides, there are reports indicating adverse effects of neonicotinoid insecticides on reproduction. Our aim was to assess the effects of ...exposure to low doses of imidacloprid on antioxidant state, DNA damage, and concentration of essential elements in the testes and epididymis using a rat model. Adult male Wistar rats were orally treated with doses comparable to currently proposed health-based reference values: 0.06 (ADI), 0.80 (10× AOEL), or 2.25 (1/200 LD
) mg/kg b.w./day for 28 consecutive days. Exposure to 2.25 mg/kg b.w./day of imidacloprid resulted in a significantly lower testis weight (1.30 ± 0.17 g compared to 1.63 ± 0.15 g in controls). Treatment with 0.06 mg/kg b.w./day increased the level of reduced glutathione in the epididymis (73%), while the activities of epididymal glutathione peroxidase and superoxide dismutase significantly increased in all treated rats (74-92% and 26-39%, respectively). Exposure to imidacloprid resulted in a low, but significant, level of DNA damage in testicular sperm cells regardless of the concentration applied (<28% compared to the negative control). Higher concentrations of Mo were measured in the testes of rats treated with 0.80 and 2.25 mg/kg b.w./day (72.9 ± 7.9 and 73.9 ± 9.1 mg/g, respectively) compared to the control animals (60.5 ± 7.8 mg/g). Higher concentrations of Na were measured in the testes of rats treated with 2.25 mg/kg b.w./day (1679 ± 82 mg/g compared to 1562 ± 56 mg/g in controls). The fact that such low doses of imidacloprid were able to produce measurable biological effects calls for the further evaluation of this widely used insecticide.
To contribute new information to the pyrethroid pesticide α-cypermethrin toxicity profile, we evaluated its effects after oral administration to Wistar rats at daily doses of 2.186, 0.015, 0.157, and ...0.786 mg/kg bw for 28 days. Evaluations were performed using markers of oxidative stress, cholinesterase (ChE) activities, and levels of primary DNA damage in plasma/whole blood and liver, kidney, and brain tissue. Consecutive exposure to α-cypermethrin affected the kidney, liver, and brain weight of rats. A significant increase in concentration of the thiobarbituric acid reactive species was observed in the brain, accompanied by a significant increase in glutathione peroxidase (GPx) activity. An increase in GPx activity was also observed in the liver of all α-cypermethrin-treated groups, while GPx activity in the blood was significantly lower than in controls. A decrease in ChE activities was observed in the kidney and liver. Treatment with α-cypermethrin induced DNA damage in the studied cell types at almost all of the applied doses, indicating the highest susceptibility in the brain. The present study showed that, even at very low doses, exposure to α-cypermethrin exerts genotoxic effects and sets in motion the antioxidative mechanisms of cell defense, indicating the potential hazards posed by this insecticide.
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