Metabolism of benzo(a)pyrene by aortic subcellular fractions in the setting of abdominal aortic aneurysms

Abstract

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.

Challenges in Predicting the Change in the Cumulative Exposure of New Tobacco and Related Products Based on Emissions and Toxicity Dose–Response Data

“…Because of profound differences in lipid homeostasis between humans and mice, genetically engineered mouse models have been developed (e.g., ApoE -/- knockout model) to alter the disease development to resemble human lesions [ 27 ]. Unfortunately, to date, only acrolein [ 28 ], arsenic [ 29 , 30 , 31 , 32 , 33 , 34 ], benzo[a]pyrene [ 35 , 36 , 37 , 38 , 39 ], and nicotine [ 40 ] have been tested in this transgenic mouse model. We considered this dataset too limited to be sufficient for the derivation of RPFs to estimate the CCE, as it should be representative of the mixture of compounds.…”

Benzo(a)pyrene and cardiovascular diseases: An overview of pre-clinical studies focused on the underlying molecular mechanism

“…However, it is only in recent years, the cardiovascular toxicity of BaP attracted considerable attention. Currently, as an independent risk factor for CVDs, BaP has been found to be closely related to CVDs, including AS, HTN and AAA, and shows multiple kinds of vascular toxicity ( 10 , 11 , 13 , 42 ). Preclinical studies have found that BaP exposure is correlated with oxidative stress and vascular toxicity.…”

“…They usually cause no symptoms, except during rupture. Smoking and advanced age are the primary risk factors for AAA; if ruptured, the mortality is 85−90% ( 42 , 92 ).…”

“…BaP increases macrophage infiltration, activates NF-κB, upregulates MMP2, MMP9, and MMP12 expression, elastic lamina disorder, and VSMCs loss ( 79 ), which increased AAA formation and rupture in C57/B6J mice ( 80 ). Furthermore, the metabolites of BaP such as 7,8-dihydrodiol, 3,6-, and 6,12-dione metabolites are reported involvement in BaP induced abdominal aortic toxicity via elevating plasma ROS levels and increased protein expression of TNFα, CYP1A1, and MMP9 ( 42 ).…”

Aortic Injury Induced by Benzo(a)pyrene and Atherogenic Diet Increased Hepatic FGF21 Expression in C57BL/6J Mice

“…Cigarette smoking is a major source of PAH for the general population (2). Benzo(a)pyrene (BaP), a PAH present in tobacco smoke, has been suggested as the cause of human diseases, including cancers and cardiovascular diseases (3)(4)(5).…”