Abstract:
Arsenic 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.
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)
