International Journal of Hygiene and Environmental Health
Chronic low level arsenic exposure evokes inflammatory responses and DNA damage
Introduction
The environmental hazard of groundwater arsenic (As) contamination has engulfed nine out of nineteen districts (Dey et al., 2014) of West Bengal, India since the first report of this problem in the lower Ganga basin of the state (Garai et al., 1984). Long term exposure to inorganic As has been associated with several types of skin lesions such as rain drop pigmentation, hypopigmentation, hyperpigmentation, keratosis and hyperkeratosis (Guha Mazumder, 2003) and other clinical complications like cardiovascular diseases (States et al., 2009) diabetes mellitus (Tseng, 2004), neuropathies (Ghosh et al., 2007) and liver diseases (Das et al., 2012). Skin and several types of internal cancers including bladder, kidney, liver, prostate, and lung have been reported with chronic exposure to As (Martinez et al., 2011). Considering this, the World Health Organization (WHO) and the U.S. Environmental Protection Agency (USEPA) has set the maximum contaminant level of inorganic As in drinking water as 10 μg/L (WHO, 2012; USEPA website). In India, Bureau of Indian Standards (BIS) has set the desirable drinking water standards for As at 10 μg/L but the legally enforceable standard is 50 μg/L if alternative sources are unavailable (BIS, 2009).
Inflammation is a protective response for cellular or tissue damage against various pathogens, damaged cells, or toxic insults (Ferrero-Miliani et al., 2007). Long persistence of inflammation or chronic inflammation may lead to the occurrence of different types of diseases including malignancies (Coussens and Werb, 2002). Toll like receptors (TLRs) activate inflammatory responses, innate immune responses, and adaptive immune responses to combat the effect of pathogens and irritants. CD14 serves as a receptor involved in the activation of the proinflammatory signal transduction pathway which occurs through the activation of TLR (reviewed by Kallapura et al., 2014). CD14, a glycophosphotidylinositol (GPI)-anchored protein is present predominantly on the surface of monocytes, macrophages and neutrophils, at lower levels on epithelial cells, endothelial cells and fibroblasts and also in soluble form without GPI in serum (Anas et al., 2010). CD14 is known to play a pivotal role in varied inflammatory disorders linked with metal toxicity (Mokgobu et al., 2015), pathogens (Beutler and Rietschel, 2003, Parajuli et al., 2012), sepsis (Huber-Lang et al., 2014), stress (Miller et al., 2014) and cancer (Khaled et al., 2014, Sellami et al., 2014).
CD14/TLR4 mediated signaling cascade for activation of transcription factor nuclear factor-κB (NF-κB) and subsequent release of cytokines and other proinflammatory mediators, by immune cells like monocytes and macrophages have been reported during gram negative bacterial infection (Jabaut and Ckless, 2012, Li and Verma, 2002). Activated NF-κB triggers the expression of mRNA of various pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukins (ILs), adhesion molecules and enzymes, such as cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), which are implicated in disease process (Adams and Hamilton, 1984, Zhao et al., 2013, Lee et al., 2012). TNF-α stimulates leukocytes and vascular endothelial cells to release other cytokines (as well as additional TNF-α), to express cell-surface adhesion molecules and to increase arachidonic acid turnover. However, the unregulated release of TNF-α into the circulation results in circulatory dysfunction, increased endothelial permeability and inflammation of different organs (Hensley et al., 2000).
Respiratory tract or lung diseases are characterized by chronic inflammation which is usually accompanied with increased expression of cytokines, chemokines, and other inflammatory target molecules like matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A2 (cPLA2) (Lee and Yang, 2013). It is suggested that oxidative stress play a crucial role in the pathophysiology of inflammation (Sies, 1986, Liaudet et al., 2009, Nathan and Cunningham-Bussel, 2013). Neutrophils and macrophages intercept and kill pathogens containing variety of pathogen-associated molecular patterns (PAMPs), primarily by production of reactive redox species, via induction of the NADPH oxidase system (Robinson, 2008, Slauch, 2011). Alveolar epithelial type II cells of lungs release inflammatory mediators and cytokines/chemokines, like IL-1β, IL-6, IL-8, and TNF-α in response to oxidative stress (Lee and Yang, 2012).
Arsenicals were reported with induction of pro inflammatory cytokines (TNF-α, IL6, IL8, IL1β) in intestinal cells, Caco-2 and human bronchial epithelial cells, HBE (Calatayud et al., 2014, Xu et al., 2013). Arsenic exposure increased susceptibility of C57BL/6 mice to respiratory infections and inflammation (Ramsey et al., 2013). Arsenic was also found to be associated with inflammation induced alteration of metabolic pathway in fatty livers of C57BL/6J mice (Shi et al., 2014). Evidence suggests that As has inductive effect on CD14 expression of human macrophages (Lemarie et al., 2006). Arsenic promulgates oxidative stress, immune dysfunction and tissue inflammatory responses, which may lead to dysregulation of NFκB signaling pathway (Hunt et al., 2014). However epidemiological studies regarding the impact of low level chronic As exposure with respect to Indian scenario are scarce. Our present work is the continuation of our previous study where we have reported induction of various pro inflammatory and inflammatory markers in chronic low level As exposed population (Sinha et al., 2014). In this study we tried to investigate whether chronic low level As exposure (11–50 μg/L) has any effect on the expression of CD14 and related inflammatory responses in the rural women of West Bengal.
Section snippets
Materials
All the reagents were of analytical grade. Milli Q (Millipore Elix 5, BM9JN2559) water was used throughout the study. Arsenic standard for AAS and 2′,7′-dichlorofluorescein diacetate (DCFH-DA) was obtained from Sigma–Aldrich Chemicals Pvt. Ltd, USA. Gelatin sepharose 4B beads were purchased from GE Healthcare Bio-Sciences AB (Uppsala, Sweden). The anti CD14 antibody and inflammatory enzyme-linked immunosorbent assay (ELISA) kits were obtained from BD Biosciences (San Jose, CA). All other
Demographic characteristics of the study population
The socioeconomic and demographic parameters of the control and exposed group of women have been depicted in Table 1. There was no significant difference between As exposed and control population with respect to age, body mass index (BMI), years of schooling, occupation, household work, household and agricultural work together, cooking fuels used at home, LPG, biomass and members in family. However family income per month had a significant difference between exposed and control women.
Arsenic level in water
We had
Discussion
Arsenic in groundwater is a worldwide public health concern. Despite of the numerous efforts for reducing the levels of As exposure it is still a dreadful threat for many countries including Bangladesh, China, Chile, Argentina, Australia, Mexico, Taiwan, Vietnam, south west United States of America and India. In all the 19 districts of West Bengal, India, analyses of 140,150 hand tube-well water samples revealed that 48.1% tube-wells had As concentrations above 10 μg/L (the WHO guideline value)
Conflict of interest
The authors declare no conflict of interest.
Acknowledgements
The authors are thankful to Indian Council of Medical Research for providing the fellowship grant of PP (3/1/3/JRF-2012/HRD-21). The authors are indebted to Prof. (Dr.) Jaydip Biswas, Director, Chittaranjan National Cancer Institute, Kolkata for providing the infrastructural facilities. The authors would like to thank Dr. Dipankar Chakraborti, Research Director, School of Environmental Studies, Jadavpur University, Kolkata for his guidance during the arsenic analyses.
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