Comparative efficacy of Nano and Bulk Monoisoamyl DMSA against arsenic-induced neurotoxicity in rats.

Chelation therapy is considered as a safe and effective strategy to combat metal poisoning. Arsenic is known to cause neurological dysfunctions such as impaired memory, encephalopathy, and peripheral neuropathy as it easily crosses the blood-brain barrier. Oxidative stress is one of the mechanisms suggested for arsenic-induced neurotoxicity. We prepared Solid Lipid nanoparticles loaded with Monoisoamyl 2, 3-dimercaptosuccinic acid (Nano-MiADMSA), and compared their efficacy with bulk MiADMSA for treating arsenic-induced neurological and other biochemical effects. Solid lipid nanoparticles entrapping MiADMSA were synthesized and particle characterization was carried out by transmission electron microscopy (TEM) and dynamic light scattering (DLS). An in vivo study was planned to investigate the therapeutic efficacy of MiADMSA-encapsulated solid lipid nanoparticles (Nano-MiADMSA; 50 mg/kg orally for 5 days) and compared it with bulk MiADMSA against sodium meta-arsenite exposed rats (25 ppm in drinking water, for 12 weeks) in male rats. The results suggested the size of Nano-MiADMSA was between 100-120 nm ranges. We noted enhanced chelating properties of Nano-MiADMSA compared with bulk MiADMSA as evident by the reversal of oxidative stress variables like blood δ-aminolevulinic acid dehydratase (δ-ALAD), Reactive Oxygen Species (ROS), Catalase activity, Superoxide Dismutase (SOD), Thiobarbituric Acid Reactive Substances (TBARS), Reduced Glutathione (GSH) and Oxidized Glutathione (GSSG), Glutathione Peroxidase (GPx), Glutathione-S-transferase (GST) and efficient removal of arsenic from the blood and tissues. Recoveries in neurobehavioral parameters further confirmed nano-MiADMSA to be more effective than bulk MiADMSA. We conclude that treatment with Nano-MiADMSA is a better therapeutic strategy than bulk MiADMSA in reducing the effects of arsenic-induced oxidative stress and associated neurobehavioral changes.

Activation of Lrrk2 and α-Synuclein in substantia nigra, striatum, and cerebellum after chronic exposure to arsenite.

Arsenic is a neurotoxin and environmental exposure to it correlates with an incidence of neurodegenerative diseases. Considering that arsenic has the potential to inhibit autophagic flux, it was hypothesized that arsenite (NaAsO2) may interplay with LRRK2 and α-Synuclein, affecting their phosphorylation in brain regions prone to neurodegeneration. After 15 weeks of chronic exposure to arsenite, a reduction in grip strength of C57BL/6 male mice was observed. Thirty minutes exposure to arsenite increased phosphorylation of Lrrk2 and α-Synuclein in organotypic brain slice cultures from the cerebellum and striatum, respectively. Chronic exposure of mice to a wide-range of concentrations of arsenite led to a significant induction of Lrrk2 phosphorylation in substantia nigra and cerebellum and α-Synuclein phosphorylation in substantia nigra and striatum. Strong correlations between phosphorylated forms of Lrrk2 and α-Synuclein in substantia nigra, Lrrk2 levels between substantia nigra and striatum, and between Lrrk2 in striatum and α-Synuclein in substantia nigra observed in control animals were completely disrupted by arsenic exposure at 50, 500, and 5000 ppb. A transcriptome analysis identified specific genes and canonical pathways that distinguish striatum, substantia nigra, and cerebellum from each other in control animals and compare individual brain regions to arsenite exposed animals. Chronic arsenite exposure altered transcripts of glutathione redox reactions and serotonin receptor signaling in striatum, axonal guidance signaling, NF-κB and androgen signaling in substantia nigra and mitochondrial dysfunction, oxidative phosphorylation, apoptosis and sirtuin signaling in the cerebellum. These data suggest that arsenite affects processes associated with neurodegenerative diseases in brain region specific manner.

Human arsenic exposure and lung function impairment in coal-burning areas in Guizhou, China.

To evaluate the effect of coal-burning arsenic (As) exposure on lung function and the potential underlying mechanisms, a total of 217 As-exposed subjects and 75 reference subjects were recruited into this study. Hair arsenic (H-As), pulmonary function tests, and serum inflammatory markers CC16, SP-A, MMP-9, and TIMP-1 were evaluated. Residents from As-exposed areas showed higher H-As concentrations (median 0.25 µg/g) than subjects from the reference area (median 0.14 µg/g). Large reductions in lung function parameters were noted in the As-exposed group. A significant negative correlation was observed between H-As concentrations and lung function. Specifically, monotonic negative dose-response relationships were observed between H-As and FEV1(%), FEV1/FVC (%) and FEF75 (%) (all P < 0.05), while the associations between H-As and FVC (%), FEF25 (%), and FEF50 (%) were nonlinear (P for nonlinearity = 0.03, 0.001, 0.01, respectively). In addition, there was a direct positive relationship between H-As and the inflammatory response. Alterations in inflammatory biomarkers (CC16, SP-A, MMP-9, and MMP-9/TIMP-1) were significantly associated with As-induced lung function impairment. Thus, this population-based study revealed that As exposure has significant toxic effects on lung function and increased inflammation may occur during this toxic process. We provide scientific evidence for an As-induced alteration in inflammatory biomarkers and pulmonary damage in an As-exposed population. The results of this study can inform risk assessment and risk control processes in relation to human As exposure in coal-burning arsenicosis areas.

Association of Arsenic Exposure With Cardiac Geometry and Left Ventricular Function in Young Adults.

BACKGROUND: Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning. METHODS: A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up. RESULTS: Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8-6.9) µg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05-2.08) in all participants and of 1.58 (1.04-2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure. CONCLUSIONS: Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.

Prepubertal exposure to low doses of sodium arsenite impairs spermatogenesis and epididymal histophysiology in rats.

For the first time, juvenile toxicity of inorganic arsenic (As) was investigated in male rats, focusing on reproductive effects. As is a metalloid naturally occurring in the environment, being the inorganic forms the most toxics. Contaminated drinking water and agricultural products are the main prospectors of intoxication for general population. In the present study, Wistar male rats (21 days old) were distributed into three groups (n = 10/group): control (received vehicle-filtered drinking water), As1 (received AsNaO2 at 0.01 mg L-1 ) and As2 (received AsNaO2 at 10 mg L-1 ). The animals were euthanized on PND 53. Testicular damages increased in As1 and As2 compared to control (ie, presence of vacuolization, acidophilic cells, and epithelium degeneration). Testicular interstitium of As1 and As2 presented fluid's increase and intense inflammatory infiltration. In the epididymis there was reduction of sperm amount in the lumen, besides epithelium areas presenting cribriform aspect in As1 and As2, exfoliation of cells in the light (in As1) and vacuoles (in As2). In epididymis interstitium, inflammatory infiltrates were observed in initial segment of As1 and As2. AsNaO2 changed immunolabeling pattern for androgen receptor in epididymis of As2, although serum testosterone levels was statistically comparable to control. Mass spectrometry revealed higher As concentrations in testis and epididymis of As2 compared to As1 and Control. These results indicate compromise of spermatogenesis and epididymal histophysiology in AsNaO2 -treated animals, possibly impairing sperm quality and fertility in long-term, even at low levels of exposure. Investigations about the reversibility of reproductive damages are necessary to better understand the mechanisms of As reproductive toxicity.

Metabolism and disposition of arsenic species from oral dosing with sodium arsenite in neonatal CD-1 mice. IV. Toxicokinetics following gavage administration and lactational transfer.

Arsenic is a ubiquitous contaminant, with typical human dietary intake below 1 µg/kg bw/d and extreme drinking water exposures up to ∼50 µg/kg bw/d. The formation and binding of trivalent metabolites are central to arsenic toxicity and strong human evidence suggests special concern for early life exposures in the etiology of adult diseases, especially cancer. This study measured the metabolism and disposition of arsenite in neonatal mice to understand the role of maturation in metabolic activation and detoxification of arsenic. Many age-related differences were observed after gavage administration of arsenite, with consistent evidence in blood and tissues for higher exposures to trivalent arsenic species in neonatal mice related to the immaturity of metabolic and/or excretory functions. The evidence for greater tissue binding of arsenic species in young mice is consistent with enhanced susceptibility to toxicity based on metabolic and toxicokinetic differences alone. Lactational transfer from arsenite-dosed dams to suckling mice was minimal, based on no dosing-related changes in the levels of arsenic species in pup blood or milk collected from the dams. Animal models evaluating whole-life exposure to inorganic arsenic must use direct dosing in early neonatal life to predict accurately potential toxicity from early life exposures in children.

Decreased regional cerebral blood flow in patients with diphenylarsinic acid intoxication.

BACKGROUND AND PURPOSE: Diphenylarsinic acid (DPAA) intoxication caused by drinking contaminated well water was found in Kamisu, Japan. The symptoms indicated cerebellar-brainstem and temporo-occipital involvement. However, it remains unclear how it affects the human brain. To elucidate the effect of DPAA on the human brain, we analyzed cerebral blood flow (CBF) data after the drinking of DPAA-contaminated water was stopped and investigated the correlation between DPAA exposure level and CBF by single-photon emission computed tomography (CBF-SPECT). METHODS: The DPAA-exposed inhabitants (n = 78) were divided into 35 symptomatic and 43 asymptomatic subjects and compared with 38 healthy controls. The DPAA concentration in nails or hair and well water was measured using a high-performance liquid chromatography system and coupled plasma mass spectrometry after adequate extraction treatment. CBF-SPECT data, obtained within 1 year after the drinking of contaminated well water was stopped, were analyzed by statistical parametric mapping. We also examined the relationship between variations in CBF-SPECT signals and variations in DPAA concentrations in the hair or nails of the subjects. RESULTS: Compared with control subjects, CBF in symptomatic DPAA-exposed subjects was significantly lower in the occipital lobe, including the cuneus and inferior occipital gyri. The DPAA concentration in the nails or hair of subjects was inversely and significantly related to their CBF. CONCLUSION: These data suggest that CBF-SPECT may be useful as a clinical marker to infer the effect of accumulated DPAA on the brain.

Influence of age on arsenic-induced behavioral and cholinergic perturbations: Amelioration with zinc and α-tocopherol.

This study was planned to determine arsenic (As) (10 mg/kg body weight given through oral gavage) induced behavioral and cholinergic perturbations in three different age groups of rats; young (postnatal day 21), adult (3 months), and aged (18 months) at 7 days post-acute exposure ( n = 6 for each of the four groups of all three age points). Further, we also evaluated the ameliorative effect of essential metal zinc (Zn; 0.02% through drinking water) and an antioxidant, α-tocopherol (vitamin E; 125 mg/kg body weight through oral gavage) against As-induced neurotoxicity. As exposure showed significant alterations in behavioral functions (open-field behavior, total locomotor activity, grip strength, exploratory behavior, and water maze learning). Cholinergic studies in three brain regions (cerebral cortex, cerebellum, and hippocampus) of different age groups also showed significant increase in acetylcholine levels and a decrease in acetylcholinesterase activity. These effects were more pronounced in hippocampus followed by cerebral cortex and cerebellum. Among the three different age points, aged animals were found to be more vulnerable to the As-induced toxicity as compared to young and adult animals suggesting that As neurotoxicity is age dependent. These As-induced alterations were significantly reversed following supplementation with Zn or vitamin E. However, vitamin E was found to elicit greater protection as compared to Zn in restoring the altered behavioral and cholinergic perturbations, providing evidence for As-induced oxidative damage.

α-Lipoic acid inhibits testicular and epididymal oxidative damage and improves fertility efficacy in arsenic-intoxicated rats.

The present study evaluates the protective effect of α-lipoic acid (LA) against arsenic-induced testicular and epididymal oxidative damage in rats. Arsenic caused significant reduction in the reproductive organ weights, serum testosterone levels, testicular daily sperm count, epididymal sperm count, sperm motility, sperm viability, and sperm membrane integrity. Significant reduction in the activity levels of superoxide dismutase, catalase, and glutathione levels with a concomitant increase in the lipid peroxidation and protein carbonyl content in the testis and the cauda epididymis of arsenic-exposed rats. Arsenic intoxication also enhanced the testicular caspase-3 mRNA levels, disorganization of testicular and cauda epididymal architecture as well as increased arsenic content in the testis and the cauda epididymis of rats. Arsenic exposure also deteriorated fertility ability in male rats over controls. Conversely, α-LA negated the testicular and cauda epididymal oxidative stress and restored the male reproductive health in arsenic-exposed rats.

Neurotoxicity of Metal Mixtures.

Metals are the oldest toxins known to humans. Metals differ from other toxic substances in that they are neither created nor destroyed by humans (Casarett and Doull's, Toxicology: the basic science of poisons, 8th edn. McGraw-Hill, London, 2013). Metals are of great importance in our daily life and their frequent use makes their omnipresence and a constant source of human exposure. Metals such as arsenic [As], lead [Pb], mercury [Hg], aluminum [Al] and cadmium [Cd] do not have any specific role in an organism and can be toxic even at low levels. The Substance Priority List of Agency for Toxic Substances and Disease Registry (ATSDR) ranked substances based on a combination of their frequency, toxicity, and potential for human exposure. In this list, As, Pb, Hg, and Cd occupy the first, second, third, and seventh positions, respectively (ATSDR, Priority list of hazardous substances. U.S. Department of Health and Human Services, Public Health Service, Atlanta, 2016). Besides existing individually, these metals are also (or mainly) found as mixtures in various parts of the ecosystem (Cobbina SJ, Chen Y, Zhou Z, Wub X, Feng W, Wang W, Mao G, Xu H, Zhang Z, Wua X, Yang L, Chemosphere 132:79-86, 2015). Interactions among components of a mixture may change toxicokinetics and toxicodynamics (Spurgeon DJ, Jones OAH, Dorne J-L, Svendsen C, Swain S, Stürzenbaum SR, Sci Total Environ 408:3725-3734, 2010) and may result in greater (synergistic) toxicity (Lister LJ, Svendsen C, Wright J, Hooper HL, Spurgeon DJ, Environ Int 37:663-670, 2011). This is particularly worrisome when the components of the mixture individually attack the same organs. On the other hand, metals such as manganese [Mn], iron [Fe], copper [Cu], and zinc [Zn] are essential metals, and their presence in the body below or above homeostatic levels can also lead to disease states (Annangi B, Bonassi S, Marcos R, Hernández A, Mutat Res 770(Pt A):140-161, 2016). Pb, As, Cd, and Hg can induce Fe, Cu, and Zn dyshomeostasis, potentially triggering neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Additionally, changes in heme synthesis have been associated with neurodegeneration, supported by evidence that a decline in heme levels might explain the age-associated loss of Fe homeostasis (Atamna H, Killile DK, Killile NB, Ames BN, Proc Natl Acad Sci U S A 99(23):14807-14812, 2002).The sources, disposition, transport to the brain, mechanisms of toxicity, and effects in the central nervous system (CNS) and in the hematopoietic system of each one of these metals will be described. More detailed information on Pb, Mn, Al, Hg, Cu, and Zn is available in other chapters. A major focus of the chapter will be on Pb toxicity and its interaction with other metals.

Assessment of heart rate response to exercise and recovery during treadmill testing in arsenic-exposed workers.

BACKGROUND: Arsenic exposure is associated with various cardiovascular diseases. The aim of the present study was to assess cardiac autonomic function via heart rate response to exercise and recovery period of treadmill testing in arsenic-exposed workers. METHODS: Sixty-five (65) occupationally arsenic-exposed workers and 35 healthy controls were enrolled. Blood and urinary arsenic levels were analyzed and symptom limited maximal treadmill exercise test were performed. Chronotropic response to exercise including age-predicted maximal heart rate (APMHR), heart rate reserve (HRreserve ), age-predicted HRreserve (APHRreserve ) and adjusted HRreserve and 1st-, 2nd-and 3rd-min heart rate recovery (HRR) indices were calculated. RESULTS: Baseline clinical and echocardiographic parameters, exercise test duration, resting and maximal heart rate, peak exercise capacity, HRreserve , APMHR, APHRreserve , and adjusted HRreserve were found to be similar between groups. HRR1 (22.0 ± 4.3 vs. 24.3 ± 3.1 bpm, p = .003) and HRR2 (43.2 ± 6.2 vs. 46.7 ± 6.4 bpm, p = .012) were significantly lower in arsenic-exposed workers compared to controls. Blood and urinary arsenic levels negatively correlated with HRR1 (r = -.477, p < .001 and r = -.438, p < .001, respectively) and HRR2 (r = -.507, p < .001 and r = -.412, p < .001 respectively). CONCLUSIONS: Arsenic-exposed workers had lower HRR indices than normal subjects but chronotropic response were similar. Cardiac autonomic dysregulation may be one of the cardiovascular consequences of arsenic exposure.

Inhibition of Oxidative Stress and Enhancement of Cellular Activity by Mushroom Lectins in Arsenic Induced Carcinogenesis.

Chronic arsenicosis is a major environmental health hazard throughout the world, including India. Animals and human beings are affected due to drinking of arsenic contaminated ground water, due to natural mineral deposits, arsenical pesticides or improperly disposed arsenical chemicals. Arsenic causes cancer with production of free radicals and reactive oxygen species (ROS) that are neutralized by an elaborate antioxidant defense system consisting of enzymes and numerous non-enzymatic antioxidants. Dietary antioxidant supplements are useful to counteract the carcinogenesis effects of arsenic. Oyster mushroom lectins can be regarded as ingredients of popular foods with biopharmaceutical properties. A variety of compounds have been isolated from mushrooms, which include polysaccharides and polysaccharopeptides with immune-enhancing effects. Lectins are beneficial in reducing arsenic toxicity due to anticarcinogenetic roles and may have therapeutic application in people suffering from chronic exposure to arsenic from natural sources, a global problem that is especially relevant to millions of people on the Indian subcontinent.

Knockout of arsenic (+3 oxidation state) methyltransferase results in sex-dependent changes in phosphatidylcholine metabolism in mice.

Arsenic (+3 oxidation state) methyltransferase is the key enzyme in the methylation pathway for inorganic arsenic. We have recently shown that As3mt knockout (KO) has a profound effect on metabolomic profiles in mice. Phosphatidylcholine species (PCs) were the largest group of metabolites altered in both plasma and urine. The present study used targeted analysis to investigate the KO-associated changes in PC profiles in the liver, the site of PC synthesis. Results show that As3mt KO has a systemic effect on PC metabolism and that this effect is sex dependent.

Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (p< 0.000001) following arsenic exposure: inorganic arsenic (iAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; p< 0.00001) and MMA (SMD: 0.49; 95% CI: 0.21-0.77; p = 0.0006) also increase, while the percentage of DMA (SMD: -0.57; 95% CI: -0.80--0.31; p< 0.0001), primary methylation index (SMD: -0.57; 95% CI: -0.94--0.20; p = 0.002), and secondary methylation index (SMD: -0.27; 95% CI: -0.46--0.90; p = 0.004) decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review.

Arsenic is a toxic metalloid present ubiquitously on earth. Since the last decade, it has gained considerable attention due to its severe neurotoxic effects. Arsenic can cross the blood-brain barrier and accumulate in different regions of the brain suggesting its role in neurological diseases. Arsenic exposure has been associated with reactive oxygen species generation, which is supposed to be one of the mechanisms of arsenic-induced oxidative stress. Mitochondria, being the major source of reactive oxygen species generation may present an important target of arsenic toxicity. It is speculated that the proper functioning of the brain depends largely on efficient mitochondrial functions. Multiple studies have reported evidence of brain mitochondrial impairment after arsenic exposure. In this review, we have evaluated the proposed mechanisms of arsenic-induced mitochondrial oxidative stress and dysfunction. The understanding of molecular mechanism of mitochondrial dysfunction may be helpful to develop therapeutic strategies against arsenic-induced neurotoxicity. The ameliorative measures undertaken in arsenic-induced mitochondrial dysfunction have also been highlighted.

Arsenic, reactive oxygen, and endothelial dysfunction.

Human exposure to drinking water contaminated with arsenic is a serious global health concern and predisposes to cardiovascular disease states, such as hypertension, atherosclerosis, and microvascular disease. The most sensitive target of arsenic toxicity in the vasculature is the endothelium, and incubation of these cells with low concentrations of arsenite, a naturally occurring and highly toxic inorganic form of arsenic, rapidly induces reactive oxygen species (ROS) formation via activation of a specific NADPH oxidase (Nox2). Arsenite also induces ROS accumulation in vascular smooth muscle cells, but this is relatively delayed because, depending on the vessel from which they originate, these cells often lack Nox2 and/or its essential regulatory cytosolic subunits. The net effect of such activity is attenuation of endothelium-dependent conduit artery dilation via superoxide anion-mediated scavenging of nitric oxide (NO) and inhibition and downregulation of endothelial NO synthase, events that are temporally matched to the accumulation of oxidants across the vessel wall. By contrast, ROS induced by the more toxic organic trivalent arsenic metabolites (monomethylarsonous and dimethylarsinous acids) may originate from sources other than Nox2. As such, the mechanisms through which vascular oxidative stress develops in vivo under continuous exposure to all three of these potent arsenicals are unknown. This review is a comprehensive analysis of the mechanisms that mediate arsenic effects associated with Nox2 activation, ROS activity, and endothelial dysfunction, and also considers future avenues of research into what is a relatively poorly understood topic with major implications for human health.

Chronic lung disease and detection of pulmonary artery dilatation in high resolution computerized tomography of chest in chronic arsenic exposure.

Lung affection in chronic arsenicosis developing from chronic ingestion of arsenic contaminated groundwater has been known but little is known on its effect on pulmonary arterial system. A cross sectional study was carried out at two geographically similar areas and demographically similar populations with or without evidence of chronic arsenic exposure in West Bengal, India. The willing participants in both the groups with chronic respiratory symptoms were evaluated with High Resolution Computerized Tomography (HRCT) of Chest. Evaluation of High Resolution Computerized Tomography of chest followed clinical assessment of lung disease in194 and 196 subjects from the arsenic exposed and unexposed people; the former had a higher prevalence of cough OR(Odds Ratio) 3.23 (95% CI(Confidence Interval): 1.72-6.07) and shortness of breath OR1.76 (95% CI: 0.84-3.71), respectively. The arsenic exposed individuals showed higher score for bronchiectasis [mean ± SD(Standard Deviation)] as 2.41 ± 2.32 vs. 1.22 ± 1.48 (P <0.001), pulmonary artery branch dilatation (PAD) as 2.48 ± 2.33 vs. 0.78 ± 1.56, (P <0.001) and pulmonary trunk dilatation as 0.26 ± 0.45 vs. nil. Age-adjusted prevalence odds ratio (POR) for Pulmonary Artery Dilatation Found in HRCT comparing those exposed to arsenic (Group 1) to unexposed participants (Group 2) was found to be 6.98 (CI: 2.26-16.48). There was a strong dose-response relationship between the PAD (Pulmonary Artery Dilatation) and cumulative arsenic exposure. Pulmonary trunk and branch dilatation in chronic arsenicosis is a frequent abnormality seen in HRCT Chest of arsenicosis patients. The significance of such finding needs further investigation.