title: In vitro neurotoxic Fe(III) and Fe(III)-chelator activities in rat hippocampal cultures. From neurotoxicity to neuroprotection prospects.
abstract: It is well known that iron dysregulation is involved in a number of processes involving genetic and non-genetic factors leading to neurodegeneration. Molecules bearing iron or influencing iron metabolism reflect directly into the levels of that redox active metal, present as Fe(II)/Fe(III), in the brain. In turn, iron level variations are associated with chemical reactivity disrupting iron homeostasis, generating variable neurotoxic iron forms and contributing to the vulnerability of cells toward oxidative stress and neuronal death in Alzheimer's disease (AD). Efforts to delineate the interactions of neurotoxic Fe(III) with low molecular mass substrates, relevant to cellular processes, led to the discovery of specific well-defined binary iron-quinate (FeQ) species. Poised to investigate the specific effects of a) well-defined forms of labile soluble Fe(III), b) the nature and chemistry of the ligand bound to Fe(III), and c) a natural metal ion binder - quinic acid - acting as a potential neuroprotectant toward iron toxicity, FeCl(3), FeQ, and free quinate were employed in in vitro studies involving primary rat hippocampal cultures. Three hour and 24-hour exposures of such cultures to Fe(III) reveal significant differential effects on both glial and neuronal cell survival linked to neurotoxicity of the specific yet variably composed complex forms of iron. The use of quinic acid both in the free and bound form to Fe(III) a) exemplifies essential structural and chemical attributes of naturally encountered metal ion binders promoting well-defined interactions with neurotoxic Fe(III), and b) signifies the potential linkage of labile Fe(III) chemical reactivity in neurodegeneration with natural substrate neuroprotection.
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Christiane M
authors.initials: CM
authors.lastname: Nday
authors.forename: Gensila
authors.initials: G
authors.lastname: Malollari
authors.forename: Savvas
authors.initials: S
authors.lastname: Petanidis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Salifoglou
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology*; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress; D011801:Quinic Acid / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002614:Chelating Agents; D056831:Coordination Complexes; D005290:Ferric Compounds; D018696:Neuroprotective Agents; D011801:Quinic Acid