Acrolein consumption induces systemic dyslipidemia and lipoprotein modification

Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202, USA.
Toxicology and Applied Pharmacology (Impact Factor: 3.71). 02/2010; 243(1):1-12. DOI: 10.1016/j.taap.2009.12.010
Source: PubMed


Aldehydes such as acrolein are ubiquitous pollutants present in automobile exhaust, cigarette, wood, and coal smoke. Such aldehydes are also constituents of several food substances and are present in drinking water, irrigation canals, and effluents from manufacturing plants. Oral intake represents the most significant source of exposure to acrolein and related aldehydes. To study the effects of short-term oral exposure to acrolein on lipoprotein levels and metabolism, adult mice were gavage-fed 0.1 to 5 mg acrolein/kg bwt and changes in plasma lipoproteins were assessed. Changes in hepatic gene expression related to lipid metabolism and cytokines were examined by qRT-PCR analysis. Acrolein feeding did not affect body weight, blood urea nitrogen, plasma creatinine, electrolytes, cytokines or liver enzymes, but increased plasma cholesterol and triglycerides. Similar results were obtained with apoE-null mice. Plasma lipoproteins from acrolein-fed mice showed altered electrophoretic mobility on agarose gels. Chromatographic analysis revealed elevated VLDL cholesterol, phospholipids, and triglycerides levels with little change in LDL or HDL. NMR analysis indicated shifts from small to large VLDL and from large to medium-small LDL with no change in the size of HDL particles. Increased plasma VLDL was associated with a significant decrease in post-heparin plasma hepatic lipase activity and a decrease in hepatic expression of hepatic lipase. These observations suggest that oral exposure to acrolein could induce or exacerbate systemic dyslipidemia and thereby contribute to cardiovascular disease risk.

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    • "That this idea has toxico logical plausibility is suggested by epidemio logical and experimental research indicating an association between environmental toxicant exposure (e.g., pesti cides, heavy metals, industrial chemicals) and an increase in the incidence and severity of many human diseases (Brown et al. 2005, 2006; Grandjean and Landrigan 2006; Kamel and Hoppin 2004; Landrigan et al. 2005; O'Toole et al. 2008). With specific reference to environmental type-2 alkene exposure, research has shown that dietary consumption of acrolein exacerbates myocardial ischemic injury and atherosclerosis in mice by interacting with endogenous unsaturated aldehydes generated during ongoing oxidative stress (Conklin et al. 2010; Ismahil et al. 2011; Luo et al. 2007; Srivastava et al. 2011; Wang et al. 2008). On the basis of these studies it has been proposed that chronic environmental exposure to unsaturated aldehydes is a significant risk factor for cardio vascular diseases (Luo et al. 2007; O'Toole et al. 2008; Wang et al. 2008). "
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    • "The daily human consumption of unsaturated aldehydes is estimated to be Ϸ5 mg/kg b.wt. No hepatocellular damage was observed in mice exposed to this dose of acrolein (Conklin et al., 2010), indicating that 5 mg/kg b.wt. is a sublethal concentration of acrolein. Significant damage to the liver was observed when mice were administered an acrolein dose of 10 mg/kg. "
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