Low level and sub-chronic exposure to methylmercury induces hypertension in rats: nitric oxide depletion and oxidative damage as possible mechanisms.
ABSTRACT Increased risk of hypertension after methylmercury (MeHg) exposure has been suggested. However, the underlying mechanisms are not well explored. In this paper, we have analyzed whether sub-chronic exposure to MeHg increases systolic blood pressure even at very low levels. In addition, we analyzed if the methylmercury-induced hypertension is associated with a decreased plasmatic nitric oxide levels and with a dysregulation of the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), as well as the levels of MDA and glutathione. For this study, Wistar rats were treated with methylmercury chloride (100 microg/kg per day) or vehicle. Total treatment time was 100 days. Malondialdehyde (MDA) and circulating NOx levels and superoxide dismutase (SOD) and catalase (CAT) activities were determined in plasma, whereas glutathione levels were determined in erythrocytes. Our results show that long-term treatment at a low level of MeHg affected systolic blood pressure, increasing and reducing the levels of plasmatic MDA and NOx, respectively. However, the activity of SOD did not decrease in the MeHg exposed group when compared to the control. We found a negative correlation between plasmatic nitrite/nitrate (NOx) levels and systolic blood pressure (r = -0.67; P = 0.001), and a positive correlation between MDA and systolic blood pressure (r = 0.61; P = 0.03), thus suggesting increased inhibition of NO formation with the increase of hypertension. In conclusion, long-term exposure to a low dose of MeHg increases the systolic pressure and is associated, at least in part, with increased production of ROS as judged by increased production of malondialdehyde and depressed NO availability.
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ABSTRACT: Cross-sectional studies and animal experiments suggest that methylmercury exposure could increase the risk of hypertension. This relationship has not been evaluated in large prospective studies. Using data from previous nested case-control studies in 2 separate prospective cohorts, we measured toenail mercury, a valid biomarker of long-term methylmercury exposure, among 6045 US men and women free of hypertension at baseline. Geometric mean toenail mercury concentrations were 0.08 μg/g in the lowest quintile and 0.74 μg/g in the highest quintile, the latter corresponding with exposures ≈2.0-fold higher than the US Environmental Protection Agency reference dose. Participants were followed prospectively (mean±SD follow-up, 14.9±7.9 years) for a new self-report of physician-diagnosed hypertension (3540 cases), shown to be >95% sensitive and specific for diagnosing hypertension in these cohorts as compared with review of medical charts and direct blood pressure measurement, respectively. After adjustment for demographic, clinical, and lifestyle risk factors, the hazard ratio (95% CI) for incident hypertension in the highest versus lowest quintile of mercury exposure was 0.96 (0.84-1.09) in women, 0.82 (0.62-1.08) in men, and 0.94 (0.84-1.06) in both cohorts combined. Findings were similar when more extreme categories of mercury were compared (across deciles, with geometric mean levels in highest decile ≈2.9-fold higher than the reference dose) and in analyses stratified by fish or omega-3 consumption, selenium levels, body mass index, and age. These findings from 2 separate large prospective cohort studies do not support any clinically apparent adverse effects of methylmercury exposure on the risk of hypertension in men or women, including at levels ≤2.5-fold higher than the reference dose.Hypertension 08/2012; 60(3):645-52. · 6.87 Impact Factor
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ABSTRACT: Methylmercury-associated effects on the cardiovascular system have been documented though discrepancies exist, and most studied populations experience elevated methylmercury exposures. No paper has investigated the impact of low-level elemental (inorganic) mercury exposure on cardiovascular risk in humans. The purpose of this study was to increase understanding of the association between mercury exposure (methylmercury and elemental mercury) and blood pressure measures in a cohort of dental professionals that experience background exposures to both mercury forms. Dental professionals were recruited during the 2010 Michigan Dental Association Annual Convention. Mercury levels in hair and urine samples were analyzed as biomarkers of methylmercury and elemental mercury exposure, respectively. Blood pressure (systolic, diastolic) was measured using an automated device. Distribution of mercury in hair (mean, range: 0.45, 0.02-5.18μg/g) and urine (0.94, 0.03-5.54μg/L) correspond well with the US National Health and Nutrition Examination Survey. Linear regression models revealed significant associations between diastolic blood pressure (adjusted for blood pressure medication use) and hair mercury (n=262, p=0.02). Urine mercury results opposed hair mercury in many ways. Notably, elemental mercury exposure was associated with a significant systolic blood pressure decrease (n=262, p=0.04) that was driven by the male population. Associations between blood pressure and two forms of mercury were found at exposure levels relevant to the general population, and associations varied according to type of mercury exposure and gender.International journal of hygiene and environmental health 04/2012; · 2.64 Impact Factor
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ABSTRACT: The objective of this study was to quantify the relationship between number of dental amalgam surfaces and urinary mercury levels. This study uses participant data from a large philanthropic chronic disease prevention program in Calgary, Alberta, Canada. Urine samples were analysed for mercury levels (measured in mug/g-creatinine). T-tests were used to determine if differences in urine mercury were statistically significant between persons with no dental amalgam surfaces and one or more dental amalgam surfaces. Linear regression was used to estimate the change in urinary mercury per amalgam surface. Urinary mercury levels were statistically significantly higher in participants with amalgam surfaces, with an average difference of 0.55 mug/g-creatinine. Per amalgam surface, we estimated an expected increase of 0.04 mug/g-creatinine. Measured urinary mercury levels were also statistically significantly higher in participants with dental amalgam surfaces following the oral administration of 2,3-dimercaptopropane-l-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) which are used to mobilize mercury from the blood and tissues. Our estimates indicate that an individual with seven or more dental amalgam surfaces has 30% to 50% higher urinary mercury levels than an individual without amalgams. This is consistent with past literature that has identified seven amalgam surfaces as an unsafe level of exposure to mercury vapor. Our analysis suggests that continued use of silver amalgam dental fillings for restorative dentistry is a non-negligible, unnecessary source of mercury exposure considering the availability of composite resin alternatives.Journal of Occupational Medicine and Toxicology 08/2013; 8(1):22.