title: Ex vivo protective effects of nicotinamide and 3-aminobenzamide on rat synaptosomes treated with Aβ(1-42).
abstract: Alzheimer's disease (AD) is the most common form of dementia and is characterized by the presence of senile plaques and neurofibrillary tangles, along with synaptic loss. The underlying mechanisms of AD are not clarified yet, but oxidative stress and mitochondrial dysfunction are important factors. Overactivation of poly(adenosine diphosphate ribose) polymerase-1 (PARP-1) enzyme has been known to cause neuroinflammation and cell death in neurodegenerative processes. The aim of the present study was to investigate the protective effects of the PARP-1 inhibitors, 3-aminobenzamide (3-AB) and nicotinamide (NA), against amyloid β peptide (1-42) (Aβ(1-42))-induced oxidative damage and mitochondrial reduction capacity on isolated synaptosomes. Rats were injected intraperitoneally with 3-AB (30-100 mg kg(-1)), NA (100-500 mg kg(-1)) or with saline for 7 days. Synaptosomes were incubated with 10-30 μM Aβ(1-42) or saline for 6 h at 37 °C. Ex vivo Aβ(1-42) treatment significantly induced oxidative stress and mitochondrial dysfunction in synaptosomes of the saline group, while synaptosomes of 3-AB and NA groups showed significant decreases in lipid peroxidation, reactive oxygen species production and protein oxidation. Moreover, both NA and 3-AB were able to improve the mitochondrial reduction capacity against Aβ(1-42). These data suggest that NA and 3-AB may have protective effects in neurodegenerative processes because of the reduced levels of oxidative stress and the improvement of mitochondrial function.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey.
authors.forename: Ezgi Turunc
authors.initials: ET
authors.lastname: Bayrakdar
authors.forename: Guliz
authors.initials: G
authors.lastname: Armagan
authors.forename: Yigit
authors.initials: Y
authors.lastname: Uyanikgil
authors.forename: Lutfiye
authors.initials: L
authors.lastname: Kanit
authors.forename: Ersin
authors.initials: E
authors.lastname: Koylu
authors.forename: Ayfer
authors.initials: A
authors.lastname: Yalcin
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009536:Niacinamide / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects* / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D001549:Benzamides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C075222:amyloid beta-protein (1-42); D009536:Niacinamide; C025160:3-aminobenzamide; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: 3-aminobenzamide; Alzheimer's disease; PARP-1 inhibition; amyloid β peptide (1-42); nicotinamide; oxidative stress; synaptosome