ALUMINUM INDUCES LIPID-PEROXIDATION AND AGGREGATION OF HUMAN BLOOD-PLATELETS

Aluminum (Al3+) intoxication is thought to play a major role in the de velopment of Alzheimer's disease and in certain pathologic manifestati ons arising from long-term hemodialysis. Although the metal does not p resent redox capacity, it can stimulate tissue lipid peroxidation in a nimal models. Furthermore, in vitro studies have revealed that the flu oroaluminate complex induces diacylglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postu lated that Al3+-induced blood platelet aggregation was mediated by lip id peroxidation. Using chemiluminescence (CL) of luminol as an index o f total lipid peroxidation capacity, we established a correlation betw een lipid peroxidation capacity and platelet aggregation. Al3+(20-100 mu M) stimulated CL production by human blood platelets as well as the ir aggregation. Incubation of the platelets with the antioxidants nor- dihydroguaiaretic acid (NDGA) (100 mu M) and n-propyl gallate (NPG) (1 00 mu M), inhibitors of the lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl salicylic acid (ASA) (100 mu M), an inhibitor of the cyclooxygenase pathway, was a weaker inhibitor of both events. These findings suggest that Al3+ stimulates lipid peroxid ation and the lipoxygenase pathway in human blood platelets thereby ca using their aggregation.