Ex vivo protective effects of nicotinamide and 3-aminobenzamide on rat synaptosomes treated with A beta(1-42)


BAYRAKDAR E. T. , ARMAGAN G. , UYANIKGİL Y. , KANIT L., Koylu E. , YALÇIN A.

CELL BIOCHEMISTRY AND FUNCTION, vol.32, no.7, pp.557-564, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 32 Issue: 7
  • Publication Date: 2014
  • Doi Number: 10.1002/cbf.3049
  • Title of Journal : CELL BIOCHEMISTRY AND FUNCTION
  • Page Numbers: pp.557-564
  • Keywords: nicotinamide, 3-aminobenzamide, Alzheimer's disease, amyloid peptide (1-42), synaptosome, oxidative stress, PARP-1 inhibition, BETA-AMYLOID NEUROTOXICITY, OXIDATIVE STRESS, ALZHEIMERS-DISEASE, IN-VIVO, LIPID-PEROXIDATION, MITOCHONDRIAL DYSFUNCTION, ETHYL-ESTER, BRAIN, IMPAIRMENT, ACID

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 peptide (1-42) (A(1-42))-induced oxidative damage and mitochondrial reduction capacity on isolated synaptosomes. Rats were injected intraperitoneally with 3-AB (30-100mgkg(-1)), NA (100-500mgkg(-1)) or with saline for 7days. Synaptosomes were incubated with 10-30M A(1-42) or saline for 6h at 37 degrees C. Ex vivo A(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 A(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. Copyright (c) 2014 John Wiley & Sons, Ltd.