Paraoxonase-1 Deficiency does not Influence Clopidogrel Antiplatelet Function in Mice
نویسندگان
چکیده
Background: Clopidogrel is an antiplatelet agent used in the treatment of vascular diseases. It requires in vivo bio activation linked to the cytochrome P450. Several studies reported that paraoxonase-1 (PON1) was a crucial enzyme in clopidogrel activation, and that patients carrying a variant of the PON1192 gene polymorphism have a high risk of thrombosis. However, these reports were not confirmed by subsequent results. The present study was aimed at investigating whether PON1 deficiency affects the biological action of clopidogrel in mice. Methods: PON1-deficient mice (n = 50) and wild type animals (n = 50) received different treatments for 3 days: a) clopidogrel, b) aspirin, c) cilostazol, d) clopidogrel + aspirin, and e) clopidogrel + aspirin + cilostazol. Blood was collected for the Platelet Function Analysis (PFA-100). Results: The different anticoagulant treatments resulted in higher aggregation times in all the mice, compared to the internal PFA control; demonstrating the anti-platelet effect of these compounds. We did not observe any significant alterations on the PFA assay in PON1-deficient mice, relative to wild type animals. Conclusion: PON1 deficiency does not influence the antiplatelet action of clopidogrel in mice, and supports the proposition that this enzyme is not involved in clopidogrel bio activation.
منابع مشابه
Clarifying the importance of CYP2C19 and PON1 in the mechanism of clopidogrel bioactivation and in vivo antiplatelet response.
AIMS It is thought that clopidogrel bioactivation and antiplatelet response are related to cytochrome P450 2C19 (CYP2C19). However, a recent study challenged this notion by proposing CYP2C19 as wholly irrelevant, while identifying paraoxonase-1 (PON1) and its Q192R polymorphism as the major driver of clopidogrel bioactivation and efficacy. The aim of this study was to systematically elucidate t...
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متن کاملParaoxonase-1 Q192R polymorphism and antiplatelet effects of clopidogrel in patients undergoing elective coronary stent placement.
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متن کامل
No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting.
AIMS In clopidogrel-treated patients undergoing coronary stenting, high on-treatment platelet reactivity was linked to a higher risk of stent thrombosis (ST). Platelet response to clopidogrel is significantly influenced by genetic factors. Recently published findings showed a highly significant impact of a common polymorphism (Q192R) within the paraoxonase-1 (PON1) gene on clopidogrel treatment...
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تاریخ انتشار 2015