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Effects of hyperlipidemia on adaptive responses to repeated zinc exposure
Citation:
DYE, J. A., R. SLADE, J. K. MCGEE, R. H. JASKOT, A. J. LAGIER, AND J. Richards. Effects of hyperlipidemia on adaptive responses to repeated zinc exposure. Presented at Experimental Biology (EB) International conference, Anaheim, CA, April 24 - 28, 2010.
Impact/Purpose:
This study demonstrates that differential response to air pollutants in healthy vs susceptible individuals (e.g., with hyperlipidemia and atherosclerosis) may relate, in part, to inability to effectively generate or maintain appropriate antioxidant responses to air pollutants.
Description:
In individuals with underlying atherosclerosis and coronary heart disease (CHD), exposure to near-road air pollution correlates epidemiologically with deleterious health outcome. Associated cardiotoxicity purportedly involves generation of reactive oxygen species (ROS) and activation of various local and systemic inflammatory pathways. The present study utilized cholesterol-fed rabbits with varying degrees of hyperlipidemia [none (N), mild (M), or severe (S)] to determine whether the degree of hyperlipidemia correlated with reduced ability to endure repeated exposure to zinc (Zn, 16 ug/kg instilled intratracheally once/wk x 4 wk). Zn is a metallic subcomponent of near-road air pollution. Data revealed that prior to, during, and after Zn exposure, along with higher blood cholesterol and LDL concentrations S-rabbits had higher circulating white cell counts; but no differences in body weight, HDL, or TG levels. Acutely after the 4th Zn instillation, ECG assessment revealed that S-rabbits transiently developed flattened T waves and increased heart rates. At 24 hr, S-rabbits had decreased relative serum nitrite levels. At 48 hr, M-and S-rabbits had minor increases in NAG and heterophils in lung lavage fluid, although lung tissue ratios of reduced (GSH) to disulfide (GSSG) forms of glutathione were unchanged. Still, in M-and S-rabbits, the amount oflung GSH (ug /g tissue) was decreased. No differences were observed in cardiac glutathione levels or ratios. However, S-rabbits had decreased liver GSH levels, and moreover, reductions in liver GSH:GSSG ratios appeared to correlate with the degree of hyperlipidemia. This study suggests that increased health risk related to near-road air pollution exposure in individuals with CHD involves a complex interplay of dyslipidemia, low-grade inflammation, and tissue specific anti-oxidant deficits that impede adaption to additional pollutant-induced oxidative stress. (This abstract does not reflect US EPA policy.) Char 1863