title: Acetaminophen reduces mitochondrial dysfunction during early cerebral postischemic reperfusion in rats.
abstract: Acetaminophen, a popular analgesic and antipyretic, has been found to be effective against neuronal cell death in in vivo and in vitro models of neurological disorders. Acute neuronal death has been attributed to loss of mitochondrial permeability transition coupled with mitochondrial dysfunction. The potential impact of acetaminophen on acute injury from cerebral ischemia-reperfusion has not been studied. We investigated the effects of acetaminophen on cerebral ischemia-reperfusion-induced injury using a transient global forebrain ischemia model. Male Sprague-Dawley rats received 15mg/kg of acetaminophen intravenously during ischemia induced by hypovolemic hypotension and bilateral common carotid arterial occlusion, which was followed by reperfusion. Acetaminophen reduced tissue damage, degree of mitochondrial swelling, and loss of mitochondrial membrane potential. Acetaminophen maintained mitochondrial cytochrome c content and reduced activation of caspase-9 and incidence of apoptosis. Our data show that acetaminophen reduces apoptosis via a mitochondrial-mediated mechanism in an in vivo model of cerebral ischemia-reperfusion. These findings suggest a novel role for acetaminophen as a potential stroke therapeutic.
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, New Jersey 08854, USA.
authors.forename: Sunanda S
authors.initials: SS
authors.lastname: Baliga
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Jaques-Robinson
authors.forename: Norell M
authors.initials: NM
authors.lastname: Hadzimichalis
authors.forename: Roseli
authors.initials: R
authors.lastname: Golfetti
authors.forename: Gary F
authors.initials: GF
authors.lastname: Merrill
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D007022:Hypotension / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D000082:Acetaminophen; D045304:Cytochromes c; C506435:Casp9 protein, rat; D053453:Caspase 9