Attenuation of Aβ-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress

Fakhrul Islam, Andleeb Khan, Kumar Vaibhav, Hayate Javed, Mohd Moshahid Khan, Rizwana Tabassum, Md Ejaz Ahmed, Pallavi Srivastava, Gulrana Khuwaja, Farah Islam, Mohd Saeed Siddiqui, Mohammed M. Shafi

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Abstract

Beta-amyloid (Aβ) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and compounds that can prevent pathways of Aβ-induced neurotoxicity may be potential therapeutic agents for treatment of AD. This study examined the hypothesis that thymoquinone (TQ) would reduce oxidative stress and mitochondrial dysfunction in differentiated pheochromocytoma (PC 12) cells exposed to Aβ fragment 25-35 (Aβ25-35). To test this hypothesis, Aβ was used to induce an in vitro model of AD in differentiated PC 12 cell line of rat. After 24 h of exposure with Aβ25-35, a significant reduction in cell viability and mitochondrial membrane potential (MMP) was observed. In addition, a significant elevation in the TBARS content and nitric oxide (NO) and activity of acetylcholine esterase (AChE) was observed which was restored significantly by TQ pretreatment. Furthermore, TQ also ameliorated glutathione and its dependent enzymes (glutathione peroxidase, glutathione reductase) which were depleted by Aβ25-35 in PC 12 cells. These results were supported by the immunocytochemical finding that has shown protection of cells by TQ from noxious effects of Aβ25-35. These results indicate that TQ holds potential for neuroprotection and may be a promising approach for the treatment of neurodegenerative disorders including AD.

Original languageEnglish (US)
Pages (from-to)55-65
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume369
Issue number1-2
DOIs
Publication statusPublished - Oct 1 2012

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Keywords

  • Alzheimer's disease
  • Oxidative stress
  • PC 12 cells
  • Thymoquinone

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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