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Methylmercury-induced inhibition of paraoxonase-1 (PON1)-implications for cardiovascular risk

Ginsberg, G., Sonawane, B., Nath, R. and Lewandowski, P. 2014, Methylmercury-induced inhibition of paraoxonase-1 (PON1)-implications for cardiovascular risk, Journal of toxicology and environmental health, Part A: current issues, vol. 77, no. 17, pp. 1004-1023, doi: 10.1080/15287394.2014.919837.

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Title Methylmercury-induced inhibition of paraoxonase-1 (PON1)-implications for cardiovascular risk
Author(s) Ginsberg, G.
Sonawane, B.
Nath, R.
Lewandowski, P.
Journal name Journal of toxicology and environmental health, Part A: current issues
Volume number 77
Issue number 17
Start page 1004
End page 1023
Total pages 20
Publisher Taylor & Francis
Place of publication Abingdon, Eng.
Publication date 2014
ISSN 1528-7394
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Environmental Sciences
Public, Environmental & Occupational Health
Toxicology
Environmental Sciences & Ecology
PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH, SCI
CORONARY-ARTERY-DISEASE
HUMAN SERUM PARAOXONASE
HOMOCYSTEINE-THIOLACTONASE ACTIVITY
LOW-DENSITY-LIPOPROTEIN
INTIMA-MEDIA THICKNESS
LEAD-EXPOSED WORKERS
LONG-TERM EXPOSURE
OXIDATIVE STRESS
PON1 ACTIVITY
FISH CONSUMPTION
Summary Methylmercury (MeHg) has been associated with increased risk for cardiovascular disease in some but not all epidemiology studies. These inconsistent results may stem from the fact that exposure typically occurs in the context of fish consumption, which is also associated with cardioprotective factors such as omega-3 fatty acids. Mechanistic information may help to understand whether MeHg represents a risk to cardiovascular health. MeHg is a pro-oxidant that inactivates protein sulfhydryls. These biochemical effects may diminish critical antioxidant defense mechanism(s) involved in protecting against atherosclerosis. One such defense mechanism is paraoxonase-1 (PON1), an enzyme present on high-density lipoproteins and that prevents the oxidation of blood lipids and their deposition in vascular endothelium. PON1 is potentially useful as a clinical biomarker of cardiovascular risk, as well as a critical enzyme in the detoxification of certain organophosphate oxons. MeHg and other metals are known to inhibit PON1 activity in vitro. MeHg is associated with lowered serum PON1 activity in a fish-eating population. The implications of lowering PON1 are evaluated by predicting the shift in PON1 population distribution induced by various doses of MeHg. An MeHg dose of 0.3 μg/kg/d is estimated to decrease the population average PON1 level by 6.1% and to increase population risk of acute cardiovascular events by 9.7%. This evaluation provides a plausible mechanism for MeHg-induced cardiovascular risk and suggests means to quantify the risk. This case study exemplifies the use of upstream disease biomarkers to evaluate the additive effect of chemical toxicity with background disease processes in assessing human risk.
Language eng
DOI 10.1080/15287394.2014.919837
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2014, Taylor & Francis
Persistent URL http://hdl.handle.net/10536/DRO/DU:30070178

Document type: Journal Article
Collection: School of Medicine
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