Aluminum does not enhance beta-amyloid toxicity in rat hippocampal cultures.
A number of environmental factors have been implicated in neurodegenerative disorders, including metallotoxins such as aluminum (Al). In the present study, the toxicity of Al-quinate (AlQ), a well-characterized Al complex, was investigated in primary rat hippocampal cultures in comparison to inorganic Al (Al-S). AlQ was significantly less toxic than Al-S during both short- (3h) and long-term (24h) incubations. The neuroprotective properties of quinic acid (which constitutes the quinate moiety of AlQ) against short-term incubations with Al-S were subsequently assessed, and the organic compound was found to provide full protection, comparable to synthetic metal chelating agents desferrioxamine and clioquinol. Finally, potential synergistic actions between Al (AlQ and Al-S) and beta-amyloid (Abeta) were investigated. Neither Al form appeared to enhance Abeta toxicity, in fact, AlQ significantly reduced Abeta toxicity. Collectively, this study highlights further the impact of structural features and physiological ligands of metal complexes on toxicity profiles, and reveals promising properties of quinic acid as a metal chelator. Despite previous reports suggesting synergistic toxicity between Al and Abeta, we could not identify such a mechanism in our investigation.
Nday
Christiane M
CM
School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland, UK.
Drever
Benjamin D
BD
Salifoglou
Thanos
T
Platt
Bettina
B
D000535:Aluminum / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D007464:Clioquinol / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011801:Quinic Acid / Q000494:pharmacology; D051381:Rats
D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D011801:Quinic Acid; D007464:Clioquinol; D000535:Aluminum; D003676:Deferoxamine