title: Mixed tocopherol preparation is superior to alpha-tocopherol alone against hypoxia-reoxygenation injury.
abstract: Hypoxia-reoxygenation (H-R) is associated with alterations in oxidant-antioxidant balance and L-arginine-nitric oxide system. Tocopherols decrease the activity of reactive oxygen species (ROS) and yet are not beneficial in clinical trials. It has been proposed that mixed tocopherols as found in nature may be more tissue protective than alpha-tocopherol alone found in commercial preparations. We compared the effect of a mixed tocopherol preparation with that of alpha-tocopherol alone on superoxide dismutase (SOD) activity and iNOS expression in cultured myocytes exposed to H-R. Myocytes from Sprague-Dawley rat hearts were subjected to hypoxia for 24 h followed by reoxygenation for 3 h H-R. Parallel groups of myocytes were pretreated with alpha-tocopherol alone or a mixed-tocopherol preparation (containing alpha-, gamma-, and delta-tocopherols) (50 microM) for 30 min. H-R resulted in myocyte injury (determined by LDH release), a decrease in SOD activity and an upregulation of iNOS expression/activity. Both tocopherol preparations attenuated cell injury and markedly decreased the effects of H-R on SOD activity and iNOS expression/activity (all P < 0.05 vs H-R group, n = 5). However, mixed-tocopherol preparation was much superior to alpha-tocopherol in terms of myocyte protection from the adverse effect of H-R (P < 0.05). Lack of efficacy of commercial tocopherol preparations in clinical trials may reflect absence of gamma- and delta-tocopherols.
authors.affiliation: Department of Medicine and Physiology, University of Arkansas for Medical Science and Central Arkansas Veterans Health Care System, Little Rock, Arkansas 72205-7199, USA.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Chen
authors.forename: Dayuan
authors.initials: D
authors.lastname: Li
authors.forename: Tom
authors.initials: T
authors.lastname: Saldeen
authors.forename: Francesco
authors.initials: F
authors.lastname: Romeo
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004338:Drug Combinations; D006321:Heart / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D024505:Tocopherols / Q000378:metabolism / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol; D024505:Tocopherols