Aluminum induces lipid peroxidation and aggregation of human blood platelets.
Aluminum (Al3+) intoxication is thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations arising from long-term hemodialysis. Although the metal does not present redox capacity, it can stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro studies have revealed that the fluoroaluminate complex induces diacylglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postulated that Al(3+) -induced blood platelet aggregation was mediated by lipid peroxidation. Using chemiluminescence (CL) of luminol as an index of total lipid peroxidation capacity, we established a correlation between lipid peroxidation capacity and platelet aggregation. Al3+ (20-100 microM) stimulated CL production by human blood platelets as well as their aggregation. Incubation of the platelets with the antioxidants nor-dihydroguaiaretic acid (NDGA) (100 microM) and n-propyl gallate (NPG) (100 microM), inhibitors of the lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl salicylic acid (ASA) (100 microM), an inhibitor of the cyclooxygenase pathway, was a weaker inhibitor of both events. These findings suggest that Al3+ stimulates lipid peroxidation and the lipoxygenase pathway in human blood platelets thereby causing their aggregation.
Neiva
T J
TJ
Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Florianópolis, Brasil.
Fries
D M
DM
Monteiro
H P
HP
D'Amico
E A
EA
Chamone
D A
DA
D000328:Adult; D000535:Aluminum / Q000032:analysis / Q000494:pharmacology*; D006139:Guaiacol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D017705:Lignans / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008163:Luminescent Measurements; D010974:Platelet Aggregation / Q000187:drug effects*; D011435:Propyl Gallate / Q000494:pharmacology; D012310:Ristocetin / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology
D017705:Lignans; D012459:Salicylates; D012310:Ristocetin; C015816:dihydroguaiaretic acid; D006139:Guaiacol; D011435:Propyl Gallate; D000535:Aluminum; D007770:L-Lactate Dehydrogenase