Abstract:
Chronic 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.
Description:
This thesis is Submitted to the Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh for The Degree of Doctor of Philosophy (PhD)