Protective effects of kinetin against aluminum chloride and D-galactose induced cognitive impairment and oxidative damage in mouse

Publication date: Available online 1 September 2017
Source:Brain Research Bulletin
Author(s): Yunpeng Wei, Dan Liu, Yin Zheng, Honglian Li, Chaoshuang Hao, Wuqing Ouyang
Increasing evidence indicates that aluminum exposure and oxidative stress play crucial roles in the initiation and development of Alzheimer's disease (AD). Aluminum chloride (AlCl3) and D-galactose (D-gal) combined treatment of mice is considered as an easy and cheap way to obtain an animal model of AD. Kinetin is a plant cytokinin, which is also reported to exert neuro-protective effects in vivo and in vitro. Thus, in this study, neuro-protective effects of kinetin were investigated in an AD model of mice induced by AlCl3 and D-gal. The Morris water maze (MWM) test was performed to directly evaluate neuro-protective effects of kinetin on the memory and spatial learning abilities, while the histopathological changes were examined by hematoxylin and eosin (H & E) staining method. To further investigate mechanisms involved, Al content in cortex and hippocampus was determined. In addition, related detection kits were used to determine acetylcholine (ACh) content and activity of acetylcholinesterase (AChE). Activities of anti-oxidative enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the content of heme oxygenase-1 (HO-1) were also measured. Besides, the content of oxidative damage bio-markers including 8-iso-prostaglandin F (8-iso-PGF), advanced glycation end products (AGEs) and 8-hydroxy-2-deoxyguanosine (8-OHdG) were determined by ELISA kits. Finally, the distribution of beta-amyloid protein 1-42 (Aβ1-42) was detected by immunohistochemistry (IHC), while the expression levels of amyloidogenic proteins including β-amyloid precursor protein (APP), β-secretase, γ-secretase and Aβ1-42 were detected by western blotting (WB) method. Results showed that kinetin improved performance in MWM test, attenuated histopathological changes, reduced Al level in cortex and hippocampus, increased ACh content and decreased AChE activity. In addition, kinetin elevated activities of anti-oxidative enzymes and reduced the levels of oxidative damage biomarkers in AD model of mice. Furthermore, kinetin also increased the content of HO-1, and inhibited the distribution of Aβ1-42 and the expressions of amyloidogenic proteins (APP, β-secretase, γ-secretase and Aβ1-42) in brain tissue of AD mice. Our results indicate that kinetin has neuro-protective effects on the AD model of mice induced by AlCl3 and D-gal, suggesting that kinetin may be a candidate drug for treatment of AD.



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