Potential Protective Role of Thymoquinone on Experimentally-induced Alzheimer Rats

Abstract

Aim: To evaluate the neuroprotective potential of thymoquinine (TQ) on the oxidative stress status of the brain in aluminum chloride (AlCl3)-induced AD in rats.
 Study Design: Animal research study.
 Place and Duration of Study: King Fahd Medical Research Center (KFMRC), King Abdulaziz University, Saudi Arabia, April 2018-June 2019.
 Methodology: Thirty adult male Sprague Dawley albino rats were randomly divided into 3 groups. Group 1 (Control). Group 2 (AD): supplemented orally with AlCl3 (17 mg/kg/day) for 4 weeks. Group 3 (TQ/AD): supplemented concomitantly with oral TQ (10 mg/kg/day) and AlCl3 (17 mg/kg/day) for 4 weeks. At the end of the experiment, spatial working memory was assessed using the Y-maze spontaneous alternation test. Then, serum levels of malondialdehyde (MDA) and glutathione peroxidase enzyme (GPX) were assessed. Then, the rats were sacrificed, and the brain was isolated, and a light microscopic examination of the hippocampus was performed. Finally, the brain homogenate content of Aβ, tau protein and acetylcholine were biochemically determined.
 Results: The AD group showed a significant decreased in the spontaneous alteration performance (SAP %) in Y-maze. Also, in the AD group, serum MDA, Aβ and tau protein were significantly increased with a significant decrease of serum GPX and acetylcholine. Examination of H&E-stained sections of the hippocampus of the AD group revealed decreased thickness and disorganization of the pyramidal cell layer of CA1 and CA3 where many pyramidal cells lost their triangular shape and appeared shrunken. The molecular and polymorphic layers showed increased glial cells and congested blood capillaries. The dentate gyrus showed marked disorganization with some cell loss. Co-administration of TQ with AlCl3 in TQ/AD group, improved SAP % and significantly decreased serum MDA, Aβ, tau protein. It also increased serum GPX and acetylcholine levels. Also, TQ partially attenuated the histopathological changes in the hippocampus.
 Conclusion: TQ could mitigate the oxidative stress markers, neurodegenerative indices and histopathological alteration encountered in AD that all reflected on improving the cognitive behavior. This may implement TQ as an adjuvant medical strategy in ameliorating AD.