An experimental model to study the cytotoxic effects induced by beta-amyloid, histamine, LPS and serum from Alzheimer patients on cultured rat endothelial cells.
Lactate dehydrogenase (LDH) enzyme activity was measured in the supernatant of rat aortic endothelial cell cultures to evaluate the cytotoxic effects of two proinflammatory mediators such as LPS and histamine, as well as beta-amyloid protein (fragment 1-28) on endothelial cells. In the same culture we also studied the influence of different sera from patients with Alzheimer's disease (AD) or healthy elderly subjects. The results indicate that very low concentrations (1 microgram/ml) of beta-amyloid or histamine (1 microM) were able to produce cell damage after an incubation time of 4 h. Treatment with LPS induced cell damage at the highest concentration (2.5 micrograms/ml) after 24 h of incubation. When endothelial cells were treated with serum from AD and non-AD individuals, an inhibition of endothelial cell proliferation was observed only with activated AD serum. These results indicate that rat endothelial cell cultures represent an important model to study inflammatory mediators and to evaluate the therapeutic effect of antiinflammatory molecules in AD and other neurodegenerative disorders.
Maneiro
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Institute for CNS Disorders, Department of Biotechnology, EuroEspes, Bergondo, La Coruña, Spain.
Lombardi
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Lagares
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Cacabelos
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D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001798:Blood Proteins / Q000633:toxicity*; D002478:Cells, Cultured / Q000187:drug effects; D004727:Endothelium / Q000187:drug effects; D006632:Histamine / Q000633:toxicity*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D001798:Blood Proteins; D008070:Lipopolysaccharides; D006632:Histamine