Abstract:
Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. Therefore, this study was designed to investigate the PUA levels and its relations to the hypertension and circulating biomarkers of CVDs recruiting human subjects from arsenic-endemic and non-endemic rural areas in Bangladesh. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. The male and female study subjects in arsenic-endemic areas were 168 and 154 respectively, whereas these were, 75 and 86 respectively, in non-endemic area. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy (ICP-MS) with appropriate certified reference material (CRM). PUA levels were measured using a colorimetric method. The average PUA levels (Mean ± SE) of male study subjects in arsenic-endemic and non-endemic areas were 4.95 ± 0.96 and 4.11 ± 0.74 mg/dl respectively, whereas these were 4.29 ± 0.86 and 3.55 ± 0.84 mg/dl respectively, of female study subjects in arsenic-endemic and non-endemic areas. The differences of PUA levels in both sexes in arsenic-endemic and non-endemic areas were statistically significant (p < 0.001). Arsenic exposure (water, hair and nail arsenic concentrations) showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen (BUN) and smoking. There were dose-response relationships between arsenic exposure and PUA levels. Furthermore, diastolic blood pressure (DBP) and systolic blood pressure (SBP) showed significant positive correlations with PUA levels. The average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. Finally, it was observed that PUA levels had significant positive associations with C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Taken together, the results of this study suggested that arsenic exposure-related elevation of PUA levels might be implicated in arsenic-induced CVDs.
Description:
This thesis is Submitted to the Institute of Biological Sciences (IBSc), University of Rajshahi, Rajshahi, Bangladesh for The Degree of Doctor of Philosophy (PhD)