The Effect Of Benzo(a) Pyrene On Platelet Function And Thrombosis

Polycyclic aromatic hydrocarbon (PAHs) are a group of chemicals that consist of two or more benzene rings. PAHs are fairly stable and persistent in the environment. Benzo(a)pyrene (BaP) is a representative PAHs which is widely presented in air pollution, coal tar, and can also be found in cigarette smoke and grilled food.BaP has been extensively studied due to its wide distribution and strong carcinogenic. The major metabolic of BaP is anti-7,8-dihydrodiol-9,10-epoxide beno(a)pyrene (BPDE). BaP can form DNA adduct, thus inducing DNA damage and gene mutation. BaP can also affect neural and immune systems. Moreover, BaP has been reported to be associated with cardiovascular disease, for example, certain studies have shown that BaP can enhance atherosclerosis. However, few studies have been conducted to investigate its effect on platelet activation.As one of the active ingredients in blood, platelet plays an important role in thrombosis. Therefore, in the present study, the effects of BaP on platelet aggregation, adhersion, and activation were examined. We also used the FeCl3-induced arterial thrombosis murine model to determine the effect of BaP on thrombosis. 1. The effect of BaP on platelet aggregation. It was found that different concentration of BaP (10μmol/L, 1μmol/L, and 0.1μmol/L) did not induce platelet aggregation. On the other hand, while BaP preincubation failed to enhance platelet aggregation under collagen and thrombin stimulation, BaP preincubation significantly enhanced ADP-induced platelet aggregation.2. The effect of BaP on platelet adhesion. We used flow chamber system to study platelet adhesion. At a shear rate of 1000s-1, BaP preincubation led to significant platelet adhesion.3. The effect of BaP on platelet activation. Using whole blood flow cytometry, the expression of P-selectin, an indicator for platlet activation, was evaluated. The results showed that BaP preincubation also increased ADP-induced P-selectin expression but not thrombin-induced P-selectin expression.4. The effect of BaP on thrombosis. All mice received 10 mg/kg BaP or vehicle only by i.p. injection and anaesthetized to establish thrombus model. We evaluated the effect of BaP on thrombus formation time. Thrombus formation time of BaP-exposed animal is significantly shorter than unexposed controls.In conclusion, these data indicate that BaP can enhance thrombosis. BaP can stimulate ADP-induced platelet aggregation, platelet adhesion and P-selectin expression, probably through the interaction with ADP-mediated signal pathway.