title: Antioxidant therapy attenuates JNK activation and apoptosis in the remote noninfarcted myocardium after large myocardial infarction.
abstract: We hypothesized that the concomitant occurrence of increased oxidative stress, JNK activation, and myocyte apoptosis in the remote myocardium (RM) following a large myocardial infarction (MI) are causally related. Three days following coronary ligation, rats were randomized to treatment with probucol and PDTC (MI-T) or vehicle (MI). Control rats (C) underwent sham operation. At 7 weeks, TBARS assay showed increased level of lipid-peroxidation within the RM in the MI group vs C, which was completely inhibited in the MI-T group. Similarly, Western blot analysis showed a twofold increase in p-JNK in the MI group, vs C, which was attenuated in MI-T, a result confirmed by a JNK-kinase activity. Furthermore, apoptosis was increased within the RM in MI vs C, while this was inhibited in MI-T. We conclude that long-term antioxidant therapy with probucol and PDTC attenuates oxidative stress, JNK activation, and myocyte apoptosis within the RM after large MI.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Coppey
authors.forename: R M
authors.initials: RM
authors.lastname: Weiss
authors.forename: H J
authors.initials: HJ
authors.lastname: Oskarsson
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011341:Probucol / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D000975:Antioxidants; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D011392:Proline; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D011341:Probucol