Vitamina E, tocoferolo e derivati Different isoforms of tocopherols enhance nitric oxide synthase phosphorylation and inhibit human platelet

aggregation and lipid peroxidation: implications in therapy with vitamin E. Li D, Saldeen T, omeo !, "ehta #L. # $ardiovasc %harmacol Ther &''()*:(++,(*(. Background: alpha-Tocopherol has received much attention in the primary and secondary prevention of coronary artery disease. Absence of other isoforms, such as gamma- and deltatocopherol, in commercial preparations of vitamin E may account for the inconsistent results of clinical trials. ince platelet aggregation is intimately involved in thrombogenesis, the relative effects of alpha-, gamma-, and delta-tocopherol and their combination !ere e"amined on human platelet aggregation, lipid pero"idation, and constitutive nitric o"ide synthase #c$% & activity. 'ethods and (esults: )uman platelets !ere incubated !ith the three different isoforms of tocopherol and their combination for *+ minutes, and then A,--induced platelet aggregation measured. All three isoforms of tocopherol markedly and similarly decreased platelet aggregation in a concentration #./+-01+ micro'&-dependent manner. All three tocopherols also decreased the level of the lipid pero"idation product, malondialdehyde #',A&, and increased $% release #- 2 +.+3 vs control&. These isoforms of tocopherol did not affect c$% protein e"pression, but enhanced c$% phosphorylation in platelets. The combination of three tocopherols in a concentration found in nature !as more potent than alpha-, gamma-, or delta-tocopherol alone in this regard. 4onclusion: These observations suggest that all three ma5or isoforms of tocopherol have a similar effect on human platelet aggregation. The three isoforms appear to attenuate platelet aggregation at least in part via a decrease in free radical generation and an increase in platelet c$% activity. The combination of tocopherols has a synergistic platelet inhibitory effect. 6uture clinical trials should concentrate on the combination of these three isoforms of tocopherols Synergistic inhibition of cyclooxygenase,& expression by vitamin E and aspirin. -bate -, .ang /, Dennery %-, et al. !ree adic 0iol "ed &''')&1:((2+,((3&. The use of aspirin in rheumatoid arthritis is limited since inhibition of the pro-inflammatory en7yme cycloo"ygenase-/ occurs only at higher aspirin doses that are often associated !ith side effects such as gastric to"icity. 8sing a macrophage cell line #9::0. .A&, the present study e"plores possible synergistic effects of aspirin and vitamin E on the e"pression and activity of cycloo"ygenase-/. ;ipopolysaccharide-induced prostaglandin E#/& formation !as significantly reduced by aspirin #..++ <mgr='& or vitamin E #.++-*++ <mgr='&. >hen combined !ith vitamin E, aspirin-dependent inhibition of prostaglandin E#/& formation !as increased from 3?@ to ?3@ of control. ;ike!ise, lipopolysaccharide-induced cycloo"ygenase-/ protein and m($A e"pression !ere virtually abolished by the combined treatment of aspirin and vitamin E, !hereas the t!o agents alone !ere only modestly effective. Vitamin 4 did not mimic the actions of vitamin E under these conditions, suggesting that redo"-independent mechanisms underlie the action of vitamin E. An agreement !ith this, vitamin E and aspirin !ere !ithout effect on lipopolysaccharide-induced translocation of the redo"-sensitive transcription factor $6-kappa B. %ur results sho! that co-administration of vitamin E renders cycloo"ygenase-/ more sensitive to inhibition by aspirin by as yet unkno!n mechanisms. Thus, anti-inflammatory therapy might be successful !ith lo!er aspirin doses !hen combined !ith vitamin E, thereby possibly avoiding the side effects of the usually reBuired high dose aspirin treatment

Effects of long,term supplementation with moderate pharmacologic doses of vitamin E are saturable and reversible in patients with type ( diabetes. Engelen 4, 5eenoy 0", 6ertommen #, De Leeuw 7. -m # $lin 8utr &''')9&:((3&,((31. BA4CD(%8$,: Vitamin E supplementation has been proposed as ad5unctive therapy to counteract the increased ;,; o"idation in diabetes and thus prevent or delay cardiovascular complications. %B9E4TAVE: The ob5ective of this study !as to investigate the effect of a moderate pharmacologic dose of vitamin E for 2EF. y in patients !ith type . diabetes. ,E AD$: The study !as double blind and the sub5ects !ere randomly assigned to / groups: the supplemented group #group = n F //& received /3+ A8 #.G1 mg& (((-alpha-tocopherol * timesEd for . y and the placebo group #group -= n F //& received a placebo for G mo follo!ed by /3+ A8 #.G1 mg& (((alpha-tocopherol * timesEd for an additional G mo. (E 8;T : erum vitamin E doubled after * mo of supplementation, from a mean #HE- ,& of *G.? HE- .+.? to GG.0 HE- .1.* <mgr=molE; #-: 2 +.+++3&. Although lipid profiles, glycated hemoglobin, and blood biochemistry values did not change significantly, copper-induced in vitro pero"idi7ability of ;,; and V;,; decreased after * mo of supplementation: the production of thiobarbituric acid-reactive substances decreased by *+G+@ #-: 2 +. ++3& and the lag time for the appearance of fluorescent products increased from .+: HE- /3 to ./* HE- *+ min in group #-: F +.++/ compared !ith group -&. Vitamin E supplementation for an additional *-? mo resulted in no further changes in serum vitamin E and lipoprotein pero"idi7ability. Values returned to baseline after supplementation ended. 4%$4;8 A%$ : Because the improvement in lipoprotein pero"idi7ability is saturable and reversible, life-long supplementation !ith vitamin E should be considered in patients !ith type . diabetes. 8europrotective effect of vitamin E on the early model of %ar:inson;s disease in rat: behavioral and histochemical evidence. oghani ", 0eh<adi /. 0rain es &''()=1&:&((,&(9. There is strong evidence that o"idative stress participates in the etiology of -arkinsonIs disease #-,&. >e designed this study to investigate the neuroprotective effect of vitamin E in the early model of -,. 6or this purpose, unilateral intrastriatal G-hydro"ydopamine #./.3 JgE3 Jl& lesioned rats !ere pretreated intramuscularly !ith ,-alpha-tocopheryl acid succinate #/0 A.8.Ekg, i.m.& . h before and three times per !eek for . month post-surgery. Apomorphine- and amphetamineinduced rotational behavior !as measured postlesion fortnightly. A parallel tyrosine hydro"ylase immunoreactivity and !heat germ agglutinin-horse radish pero"idase #>DA-)(-& tract-tracing study !as performed to evaluate the vitamin E pretreatment efficacy. Tyrosine hydro"ylaseimmunohistochemical analyses sho!ed a reduction of .1@ in ipsilateral substantia nigra pars compacta # $4& cell number of the vitamin E-pretreated lesioned #;HE& group comparing !ith contralateral side. The cell number dropped to 3*@ in the lesioned #;HV& group. An addition, retrograde-labeled neurons in ipsilateral $4 !ere reduced by up to *+@ in the ;HE group and G3@ in the ;HV group. Behavioral tests revealed that there are :0@ and G1@ reductions in contraversive and ipsiversive rotations in the ;HE group, respectively, as compared !ith the ;HV group. Therefore repeated intramuscular administration of vitamin E e"erts a rapid protective effect on the nigrostriatal dopaminergic neurons in the early unilateral model of -,.