title: Acetaminophen protects hippocampal neurons and PC12 cultures from amyloid beta-peptides induced oxidative stress and reduces NF-kappaB activation.
abstract: The present findings show that an atypical non-steroidal anti-inflammatory drug, such as acetaminophen, retains the ability to recover amyloid beta-peptides driven neuronal apoptosis through the impairment of oxidative stress. Moreover, this compound reduces the increased NF-kappaB binding activity, which occurs in these degenerative conditions. Therapeutic interventions aimed at reducing the inflammatory response in Alzheimer's disease (AD) recently suggested the application of non-steroidal anti-inflammatory drugs. Although the anti-inflammatory properties of acetaminophen are controversial, it emerged that in an amyloid-driven astrocytoma cell degeneration model acetaminophen proved to be effective. On these bases, we analyzed the role of acetaminophen against the toxicity exerted by different Abeta-peptides on rat primary hippocampal neurons and on a rat pheochromocytoma cell line. We found a consistent protection from amyloid beta-fragments 1-40 and 1-42-induced impairment of mitochondrial redox activity on both cell cultures, associated with a marked reduction of apoptotic nuclear fragmentation. An antioxidant component of the protective activity emerged from the analysis of the reduction of phospholipid peroxidation, and also from a significant reduction of cytoplasmic accumulation of peroxides in the pheochromocytoma cell line. Moreover, activation of NF-kappaB by amyloid-derived peptides was greatly impaired by acetaminophen pre-treatment in hippocampal cells. This evidence points out antioxidant and anti-transcriptional properties of acetaminophen besides the known capability to interfere with inflammation within the central nervous system, and suggests that it can be exploited as a possible therapeutic approach against AD.
authors.affiliation: Pharmacology and Neuroscience, National Cancer Research Institute c/o Advanced Biotechnology Centre, L.go R. Benzi 10, 16132 Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bisaglia
authors.forename: V
authors.initials: V
authors.lastname: Venezia
authors.forename: P
authors.initials: P
authors.lastname: Piccioli
authors.forename: S
authors.initials: S
authors.lastname: Stanzione
authors.forename: C
authors.initials: C
authors.lastname: Porcile
authors.forename: C
authors.initials: C
authors.lastname: Russo
authors.forename: F
authors.initials: F
authors.lastname: Mancini
authors.forename: C
authors.initials: C
authors.lastname: Milanese
authors.forename: G
authors.initials: G
authors.lastname: Schettini
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects; D018384:Oxidative Stress; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D016328:NF-kappa B; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D000082:Acetaminophen