The potential role of tocopherol in asthma and allergies: modification of the leukotriene pathway.
Metabolism of arachidonic acid via the 5-lipoxygenase (5-LO) pathway leads to the formation of hydroperoxyeicosatetraenoic acids (HPETEs) and leukotriene (LT) A4. This unstable allylic epoxide can be further converted by secondary enzymes into LTB(4) and cysteinyl LTs. LTs represent a family of potent biologically active compounds synthesised by specific cell types and by transcellular biosynthetic mechanisms. Cysteinyl LTs are involved in the pathogenesis of asthma, and recent data indicate that individuals with asthma may have enhanced basal excretion of urinary LTE4 compared with normal individuals. Tocopherol (vitamin E) and tocopherol acetate strongly inhibit potato 5-LO in an irreversible and noncompetitive way, and, by affecting the redox state of cells possessing 5-LO, they may influence the production of biologically active LTs. It has been reported that normal plasma levels of tocopherol may enhance the lipoxygenation of arachidonic acid, whereas higher tocopherol levels exert a suppressive effect that is consistent with its role as a hydroperoxide scavenger. Receptor-mediated activation of neutrophils in individuals with asthma results in the synthesis of LTs. This activation is inhibited by tocopherol in a concentration-dependent manner. Additional controlled studies are needed to assess the effect of tocopherol on leukotriene production in asthmatic individuals. The results of these studies may be useful in developing new therapeutic approaches in asthmatic/allergic patients.
Centanni
S
S
Respiratory Unit, San Paolo Hospital, University of Milan, Milan, Italy. stefano.centanni@unimi.it
Santus
P
P
Di Marco
F
F
Fumagalli
F
F
Zarini
S
S
Sala
A
A
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000503:physiopathology*; D015289:Leukotrienes / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014810:Vitamin E / Q000627:therapeutic use*
D015289:Leukotrienes; D014810:Vitamin E