Ambreen Alamdar

Human exposure to toxic metals via contaminated dust: Bio-accumulation trends and their potential risk estimation.

We assessed the levels of potentially toxic trace metals, Zinc (Zn), Lead (Pb), Manganese (Mn), Copper (Cu), Nickel (Ni), Chromium (Cr), Cobalt (Co), and Cadmium (Cd), in dust, hair, nail and serum, sampled in rural, urban and industrial areas of Punjab, Pakistan. Trace metals occurrence in all samples, in descending order, was: Zn, Pb, Mn, Cu, Cr, Ni, Co, Cd. The samples from the urban areas showed significantly higher concentration of toxic trace metals (Zn, Ni, Cr, Co, Mn, and Cd) than those from industrial (which conversely had higher levels of Pb and Cu), and than samples from rural areas. Bioaccumulation patterns showed that dust exposure is one of the major routes into human body for Cd, Pb, Co, Mn and Cr, while the burden of Zn, Cu, and Ni can be more linked to dietary sources. The concentrations of trace metals in the samples from Punjab were comparable and/or higher than those reported worldwide. In many cases, the levels of Zn, Cr, Pb, Ni and Cd in hair and nail were beyond the ATSDR threshold guideline values that may cause some serious health effects. Hazard Index (HI) calculated for trace metal concentrations in the human population of Punjab points particularly to health risks from Cd (for children in urban and industrial areas) and from Pb (for all sub-groups).

Avian feathers as a non-destructive bio-monitoring tool of trace metals signatures: A case study from severely contaminated areas

The concentrations of trace metals were assessed using feathers of cattle egrets (Bubulcus ibis), collected within two industrial areas of Pakistan, Lahore and Sialkot. We found, in order of descending concentration: Zinc (Zn), Iron (Fe), Nickel (Ni), Copper (Cu), Cadmium (Cd), and Manganese (Mn), Chromium (Cr), Arsenic (As), and Lithium (Li), without any significant difference (except Fe, Zn, and Ni) between the two areas. The concentrations of trace metals, we recorded were among the highest ever reported in the feathers of avian species worldwide. The concentrations of Cr, Pb, Cd were above the threshold that affects bird reproductive success. The high contamination by heavy metals in the two areas is due to anthropogenic activities as well to natural ones (for As and Fe). The bioaccumulation ratios in eggs and feathers of the cattle egret, their prey, and the sediments from their foraging habitats, confirmed that avian feathers are a convenient and non-destructive sampling tool for the metal contamination. The results of this study will contribute to the environmental management of the Lahore and Sialkot industrial areas.

Organochlorine pesticides in surface soils from obsolete pesticide dumping ground in Hyderabad City, Pakistan: Contamination levels and their potential for air-soil exchange

This study was conducted to examine organochlorine pesticides (OCPs) contamination levels in the surface soil and air samples together with air-soil exchange fluxes at an obsolete pesticide dumping ground and the associated areas from Hyderabad City, Pakistan. Among all the sampling sites, concentrations of OCPs in the soil and air samples were found highest in obsolete pesticide dumping ground, whereas dominant contaminants were dichlorodiphenyltrichloroethane (DDTs) (soil: 77-212,200 ng g(-1); air: 90,700 pg m(-3)) and hexachlorocyclohexane (HCHs) (soil: 43-4,090 ng g(-1); air: 97,400 pg m(-3)) followed by chlordane, heptachlor and hexachlorobenzene (HCB). OCPs diagnostic indicative ratios reflect historical use as well as fresh input in the study area. Moreover, the air and soil fugacity ratios (0.9-1.0) at the dumping ground reflecting a tendency towards net volatilization of OCPs, while at the other sampling sites, the fugacity ratios indicate in some cases deposition and in other cases volatilization. Elevated concentrations of DDTs and HCHs at pesticide dumping ground and its surroundings pose potential exposure risk to biological organisms, to the safety of agricultural products and to the human health. Our study thus emphasizes the need of spatio-temporal monitoring of OCPs at local and regional scale to assess and remediate the future adverse implications.

Mapping human health risks from exposure to trace metal contamination of drinking water sources in Pakistan

The consumption of contaminated drinking water is one of the major causes of mortality and many severe diseases in developing countries. The principal drinking water sources in Pakistan, i.e. ground and surface water, are subject to geogenic and anthropogenic trace metal contamination. However, water quality monitoring activities have been limited to a few administrative areas and a nationwide human health risk assessment from trace metal exposure is lacking. Using geographically weighted regression (GWR) and eight relevant spatial predictors, we calculated nationwide human health risk maps by predicting the concentration of 10 trace metals in the drinking water sources of Pakistan and comparing them to guideline values. GWR incorporated local variations of trace metal concentrations into prediction models and hence mitigated effects of large distances between sampled districts due to data scarcity. Predicted concentrations mostly exhibited high accuracy and low uncertainty, and were in good agreement with observed concentrations. Concentrations for Central Pakistan were predicted with higher accuracy than for the North and South. A maximum 150-200 fold exceedance of guideline values was observed for predicted cadmium concentrations in ground water and arsenic concentrations in surface water. In more than 53% (4 and 100% for the lower and upper boundaries of 95% confidence interval (CI)) of the total area of Pakistan, the drinking water was predicted to be at risk of contamination from arsenic, chromium, iron, nickel and lead. The area with elevated risks is inhabited by more than 74 million (8 and 172 million for the lower and upper boundaries of 95% CI) people. Although these predictions require further validation by field monitoring, the results can inform disease mitigation and water resources management regarding potential hot spots.

Human Arsenic exposure via dust across the different ecological zones of Pakistan.

The present study aims to assess the arsenic (As) levels into dust samples and its implications for human health, of four ecological zones of Pakistan, which included northern frozen mountains (FMZ), lower Himalyian wet mountains (WMZ), alluvial riverine plains (ARZ), and low lying agricultural areas (LLZ). Human nail samples (N=180) of general population were also collected from the similar areas and all the samples were analysed by using ICP-MS. In general the higher levels (p<0.05) in paired dust and human nail samples were observed from ARZ and LLZ than those of other mountainous areas (i.e., WMZ and FMZ), respectively. Current results suggested that elevated As concentrations were associated to both natural, (e.g. geogenic influences) and anthropogenic sources. Linear regression model values indicated that As levels into dust samples were associated with altitude (r(2)=0.23), soil carbonate carbon density (SCC; r(2)=0.33), and population density (PD; r(2)=0.25). The relationship of paired dust and nail samples was also investigated and associations were found for As-nail and soil organic carbon density (SOC; r(2)=0.49) and SCC (r(2)=0.19) in each studied zone, evidencing the dust exposure as an important source of arsenic contamination in Pakistan. Risk estimation reflected higher hazard index (HI) values of non-carcinogenic risk (HI>1) for children populations in all areas (except FMZ), and for adults in LLZ (0.74) and ARZ (0.55), suggesting that caution should be paid about the dust exposure. Similarly, carcinogenic risk assessment also highlighted potential threats to the residents of LLZ and ARZ, as in few cases (5-10%) the values exceeded the range of US-EPA threshold limits (10(-6)-10(-4)).

Metabolomics reveals disturbed metabolic pathways in human lung epithelial cells exposed to airborne fine particulate matter

Exposure to airborne fine particulate matter (PM2.5) has been associated with a variety of adverse health effects; however, the molecular mechanisms involved in PM2.5-elicited pulmonary toxicity are still not well elucidated. By conducting an ultra-high performance liquid chromatography/mass spectrometry-based metabolomics analysis, the present study investigated alterations of metabolome in human lung epithelial cells (A549) exposed to PM2.5 extracts. Distinct metabolomic profiles were found to be associated with PM2.5 treatment. PM2.5 significantly changed the abundance of 16 intracellular metabolites in a dose-dependent manner, of which 13 were decreased and three were increased. By pathway analysis, it was shown that the citrate cycle, amino acid biosynthesis and metabolism, and glutathione metabolism were the major metabolic pathways disturbed by PM2.5 in A549 cells. In addition, changes in expression of several key genes involved in these pathways further validated the metabolic alterations observed by metabolomics herein. It is suggested that PM2.5-induced oxidative stress may contribute to perturbation of metabolic processes occurring in cell mitochondria. Overall, these results aid in improving understanding of the toxicological mechanisms related to PM2.5, and identifying potential biomarkers indicative of inhalable PM2.5 exposure.

Arsenic levels from different land-use settings in Pakistan: Bio-accumulation and estimation of potential human health risk via dust exposure

The present study aims at assessing arsenic (As) levels in outdoor dust and human exposure risks at different land use setting (i.e., rural, industrial, urban) from Punjab, Pakistan. The results showed higher As concentrations (mg/kg) in all the sample types ( i.e., dust, hair and nail) collected from industrial sites (9.78, 2.36, 2.5) followed by urban (7.59, 0.38, 0.88) and rural sites (6.95, 0.52, 1.12), respectively. In the current study, we also carried out human risk assessment via contaminated dust exposure, which suggested that dust ingestion is the major route of As contamination for the associated population, followed by the inhalation and dermal contact, at all studied land use settings. Hazard Index (HI) calculated for non-carcinogenic health risks for adults showed higher values at industrial (0.65) and urban (0.53) sites, which reflected that dust exposure is the major contributing source of human arsenic burden and may pose several adverse health effects. Carcinogenic risk values showed that at industrial areas the risk of carcinogenesis to the associated population is mainly due to As contaminated dust exposure. Hair (60%) and nail samples (70%) collected from industrial land use were found above the WHO threshold limit of 1mg/kg, suggested high risks for human health in the studied area. The results of the present study would be useful for assessing the human health risks due to arsenic contamination via dust exposure in different parts of country.

Exposure to arsenic via drinking water induces 5-hydroxymethylcytosine alteration in rat

Arsenic exposure has been implicated to alter DNA methylation process in vitro and in vivo, but it remains obscure whether it disrupts DNA demethylation process, which is pivotal for epigenetic regulation. The objective of this descriptive study was to investigate the relationship between arsenic exposure and 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) alterations in various organs. In this study, we exposed male Sprague-Dawley rats to sodium arsenite (0.5, 2 or 10 ppm) via drinking water for 8 weeks. Spleen accumulated 2- to 3-fold higher arsenic levels than liver and heart. Lower arsenic levels were observed in the kidney, pancreas and lung. No significant arsenic-induced global 5mC alterations were observed in the majority of investigated organs. However, arsenic induced organ-specific alterations of 5hmC and/or 5hmC/5mC in some investigated organs, i.e. lung, heart, kidney, pancreas and spleen. Our observations suggest that 5hmC is a more sensitive biomarker of arsenic-induced impacts on epigenetic processes than 5mC. Moreover, demethylation via hydroxylation of 5mC appears to play a central role in the toxic mechanism of arsenic.

Arsenic activates the expression of 3β-HSD in mouse Leydig cells through repression of histone H3K9 methylation

ABSTRACT Arsenic exposure has been associated with male reproductive dysfunction by disrupting steroidogenesis; however, the roles of epigenetic drivers, especially histone methylation in arsenic‐induced steroidogenic toxicity remain not well documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9) methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC‐1) due to arsenic exposure. Our results indicated that mRNA and protein expression levels of 3&bgr;‐hydroxysteroid dehydrogenase (3&bgr;‐HSD) were both significantly up‐regulated while the rest of key genes involved in steroidogenesis were down‐regulated. Moreover, arsenic exposure significantly decreased the histone H3K9 di‐ and tri‐methylation (H3K9me2/3) levels in MLTC‐1 cells. Since H3K9 demethylation leads to gene activation, we further investigated whether the induction of 3&bgr;‐HSD expression was ascribed to reduced H3K9 methylation. The results showed that H3K9me2/3 demethylase (JMJD2A) inhibitor, quercetin (Que) significantly attenuated the decrease of H3K9me2/3 and increase of 3&bgr;‐HSD expression induced by arsenic. To further elucidate the mechanism for the activation of 3&bgr;‐HSD, we determined the histone H3K9 methylation levels in Hsd3b gene promoter, which also showed significant decrease of H3K9me2/3 in the investigated region after arsenic exposure. Considering these results, we conclude that arsenic exposure induced 3&bgr;‐HSD up‐regulation by suppressing H3K9me2/3 status, which is suggested as a compensatory mechanism for steroidogenic disturbance in MLTC‐1 cells. HIGHLIGHTSEpigenetic mechanisms of arsenic‐induced male reproductive toxicity remain unclear.Arsenic disturbs the expression of key steroidogenic genes in MLTC‐1 cells.Histone H3K9 di‐ and tri‐methylation was suppressed in arsenic‐exposed cells.Arsenic activates 3&bgr;‐HSD expression through repression of histone H3K9 methylation.

Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.