Uniform TitleAcetaminophen-mediated cardioprotection via inhibition of the mitochondrial permeability transition pore-induced apoptotic pathway
NameHadzimichalis, Norell Melissa (author), Merrill, Gary (chair), Firestein, Bonnie (co-chair), Ma, Jianjie (internal member), Bagnell, Carol (internal member), McHugh, Nansie (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectPhysiology and Integrative Biology,
Heart--Effect of drugs on
DescriptionHistorically, acetaminophen has been employed as a safe and effective analgesic and antipyretic agent. However, our laboratory has recently reported that acetaminophen also confers functional cardioprotection following cardiac insult, including ischemia/reperfusion, hypoxia/reoxygenation, and exogenous peroxynitrite and hydrogen peroxide administration. In the current study, we examined the mechanism of acetaminophen-mediated cardioprotection following ischemia/reperfusion injury. Langendorff-perfused guinea pig hearts were exposed to acute treatment with acetaminophen (0.35 mM) or vehicle (Krebs-Henseleit buffer) beginning at 15 minutes of a 30-minute baseline stabilization period. Low-flow global myocardial ischemia was subsequently induced for 30 minutes followed by 60 minutes of reperfusion. Upon completion of reperfusion, hearts were homogenized and separated into cytosolic and mitochondrial fractions. Mitochondrial swelling and mitochondrial cytochrome c release were assessed and found to be significantly and completely reduced following reperfusion in acetaminophen-treated hearts when compared to vehicle. In a separate group of hearts, ventricular myocytes were isolated and subjected to fluorescence-activated cell sorting. Acetaminophen-treated hearts showed a significant decrease in late stage apoptotic myocytes when compared to vehicle-treated hearts following injury (58 [plus/minus] 1% vs. 81 [plus/minus] 5%, respectively). These data, together with electron micrograph analysis, suggest that acetaminophen mediates cardioprotection, in part, by inhibiting the mitochondrial permeability transition pore and subsequent apoptotic pathway.
NoteIncludes bibliographical references (p. 73-79).
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.