Metabolism of benzo(a)pyrene by aortic subcellular fractions in the setting of abdominal aortic aneurysms
As exposure to polycyclic aromatic hydrocarbons (PAHs; a family of environmental toxicants) have been implicated in cardiovascular diseases, the ability of the aortic tissue to process these toxicants is important from the standpoint of abdominal aortic aneurysms and atherosclerosis. Benzo(a)pyrene (B(a)P), a representative PAH compound is released into the environment from automobile exhausts, industrial emissions, and considerable intake of B(a)P is also expected in people who are smokers and barbecued red meat eaters. Therefore, knowledge of B(a)P metabolism in the cardiovascular system will be of importance in the management of vascular disorders. Toward this end, subcellular fractions (nuclear, cytosolic, mitochondrial, and microsomal) were isolated from the aortic tissues of Apo E mice that received a 5 mg/kg/week of B(a)P for 42 days and 0.71 mg/kg/day for 60 days. The fractions were incubated with 1 and 3 μM B(a)P. Post incubation, samples were extracted with ethyl acetate and analyzed by reverse-phase HPLC. Microsomal B(a)P metabolism was greater than the rest of the fractions. The B(a)P metabolite levels generated by all the subcellular fractions showed a B(a)P exposure concentration-dependent increase for both the weekly and daily B(a)P treatment categories. The preponderance of B(a)P metabolites such as 7,8-dihydrodiol, 3,6-, and 6,12-dione metabolites are interesting due to their reported involvement in B(a)P-induced toxicity through oxidative stress.
KeywordsBenzo(a)pyrene Aortic aneurysms Atherosclerosis ApoE mouse Subcellular fractions
The research embodied in this manuscript was facilitated by The Harold Amos Faculty Development Award of the Robert Wood Johnson Foundation (Princeton, NJ), and the Vanderbilt Clinical and Translational Scholars Award to UKS. Also, funding support through the National Institutes of Health (NIH) Grants 5S11ES01415602 from the National Institute of Environmental Health Sciences (NIEHS) to UKS and AR, 5RO1CA142845-04 from the National Cancer Institute (NCI) to AR is acknowledged. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of NIH or Vanderbilt University or Meharry Medical College.
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Conflict of interest
The authors declare that they do not have any conflicts of interest.
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