PhD Thesis
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Item Investigation of Association of the Arsenic Exposure with Inflammatory, Adhesion and Angiogenic Molecules: A Cross-Sectional Study in Bangladesh(University of Rajshahi, 2014) Rahman, Md. Mashiur; Hossain, Md. KhaledArsenic is an environmental pollutant and a well established human carcinogen that causes a variety of health hazards affecting millions of people in the world. Cardiovascular diseases (CVDs) and cancer are the leading causes of arsenic-related morbidity and mortality worldwide. Atherosclerosis is the main event of CVDs, and angiogenesis is involved in the pathological development of cancer and CVDs. There are several circulating inflammatory, adhesion and angiogenic molecules that are involved in atherosclerosis and angiogenesis. Among them, C-reactive protein (CRP) as an inflammatory molecule, intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) are implicated in the development of atherosclerotic plaque, and vascular endothelial growth factor (VEGF) is involved in angiogenesis. Although arsenic exposure is associated with CVDs and cancer, the biochemical events underlying the arsenic-induced CVDs and cancer have not yet been fully documented. Therefore, this study has been designed to investigate the relationships of arsenic exposure with the circulating inflammatory, adhesion and angiogenic molecules related to CVDs and cancer. Non-endemic human subjects were selected from a village in the northern area of Bangladesh with no history of arsenic exposure, and arsenic-endemic subjects were selected from several villages in the north-west region of Bangladesh. Arsenic concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) and circulating levels of CRP, ICAM-1, VCAM-1 and VEGF were quantified using respective enzyme-linked immunosorbent assay kits through micro plate reader. Significant positive correlations were found between arsenic exposure metrics (water, hair and nails) and circulating levels of CRP, ICAM-1, VCAM-1 and VEGF. All these molecules showed dose-response relationship with arsenic exposure metrics. Further, the associations of CRP, ICAM-1, VCAM-1 and VEGF with arsenic exposure metrics were significant even adjusting for relevant covariates. Therefore, the significant positive correlations and dose-response relationships of circulating inflammatory, adhesion and angiogenic molecules with arsenic exposure metrics suggest the possible biochemical events of arsenic-induced CVDs and cancer.Item Investigation of Association of the Arsenic Exposure with Circulating Molecules Related to Bronchial Asthma(University of Rajshahi, 2015) Hossain, Md. Imam; Hossain, Md. Khaled; Nikkon, FarjanaChronic exposure to arsenic is a major threat to the public health worldwide, affecting hundreds of millions of people. Bangladesh has been grappling with the largest mass poisoning of a population in history because of the contamination of drinking water by inorganic arsenic greater than the permissive limit set by World Health Organization (WHO). Arsenic exposure has been reported to be associated with several chronic diseases including asthma. Asthma is a substantial public health problem among children and adults worldwide. There has been a sharp increase in the global prevalence, morbidity, mortality, and economic burden associated with asthma. Asthma is largely mediated by allergic reactions involving immunoglobulin E (IgE) and Interleukin 4 (IL-4). Although arsenic exposure has been reported to be associated with asthma, however, underlying mechanism linking arsenic exposure and molecules related to asthma has not yet been documented clearly. Therefore, this study was designed to explore the associations of arsenic exposure with serum IgE and IL-4 levels recruiting human populations from arsenic-endemic and non-endemic areas in Bangladesh. Non-endemic subjects were selected from a village in the northern area of Bangladesh with no history of arsenic exposure, and arsenic-endemic subjects were selected from the arsenic-contaminated north-west region of Bangladesh. Drinking water, hair, nail and blood specimens of the study populations were collected for the subsequent laboratory analysis. Arsenic levels in the drinking water, hair and nails of the study subjects were determined by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). Serum IgE and IL-4 levels were measured by commercially available ELISA kits. In this study, we found that the levels (Mean ± SE) of serum IgE and IL-4 in arsenic-endemic population were 1372.55 ± 96.74 IU/ml and 39.45 ± 1.30 pg/ml, respectively whereas these were 723.08 ± 73.57 IU/ml and 33.63 ± 1.81 pg/ml, respectively in non-endemic population. The differences of serum IgE and IL-4 levels between arsenic-endemic and non-endemic populations were statistically significant (p < 0.001 for IgE and p < 0.05 for IL4). Further serum IgE and IL-4 levels were found to be significantly (p < 0.001, p < 0.001 and p < 0.01, respectively for IgE with drinking water, hair and nail arsenic, and p < 0.01, p < 0.01 and p < 0.01, respectively for IL-4 with drinking water, hair and nail arsenic) associated with arsenic exposure metrics. Multiple regression analyses showed that only arsenic concentrations in drinking water, hair and nails but not other variables (age, sex, BMI, smoking and socioeconomic conditions) were significantly associated with serum IgE and IL-4 levels. Further, drinking water, hair and nail arsenic showed dose-response relationships with serum IgE and IL-4 levels. Intriguingly, serum IL-4 levels showed a significant (p < 0.01) positive association with circulating IgE and vascular cell adhesion molecule-1 (VCAM-1). Taken together, the results indicate that arsenic exposure-related asthma may be mediated through IgE-IL-4 sensitive pathways.