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Protective Effects of Perindopril on D-Galactose and Aluminum Trichloride Induced Neurotoxicity via the Apoptosis of Mitochondria-Mediated Intrinsic Pathway in the Hippocampus of Mice

Protective Effects of Perindopril on D-Galactose and Aluminum Trichloride Induced Neurotoxicity via the Apoptosis of Mitochondria-Mediated Intrinsic Pathway in the Hippocampus of Mice

Weina Yang, Lili Shi, Lianji Chen, Bingyi Zhang, Kaige Ma, Yong Liu, Yihua Qian

Brain Res Bull. 2014 Oct;109:46-53.

PMID: 25290208

Abstract:

Perindopril, an angiotensin converting enzyme inhibitor, has been reported to improve learning and memory in a mouse or rat model of Alzheimer's disease (AD) induced by injection of beta-amyloid protein. However, the exact mechanism of perindopril on the cognitive deficits is not fully understood. Our previous data have indicated that perindopril improves learning and memory in a mouse model of AD induced by D-galactose (D-gal) and aluminum trichloride (AlCl₃) via inhibition of acetylcholinesterase activity and oxidative stress. Whether perindopril also inhibit apoptosis to prevent cognitive decline remains unknown in mice. Therefore, the present study explored the protective effects of perindopril in the hippocampus of mice further. Perindopril (0.5 mg/kg/day) was administered intragastrically for 60 days after the mice were given a D-gal (150 mg/kg/day) and AlCl₃ (10 mg/kg/day) intraperitoneally for 90 days. Then the expression of Bcl-2, Bax, Fas, FasL, caspase-3, caspase-8 and caspase-9 were analyzed by RT-PCR and western blotting in the hippocampus. Perindopril significantly decreased caspase-3 and caspase-9 activities, and elevated Bcl-2/Bax ratio in the hippocampus. However, the expression of Fas, FasL and caspase-8 did not change in the hippocampus whether treatment with d-gal and AlCl₃ or perindopril. Taken together, the above findings indicated that perindopril inhibited apoptosis in the hippocampus may be another mechanism by which perindopril improves learning and memory functions in d-gal and AlCl₃ treated mice.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP130061288	Perindopril Related Compound D		130061-28-8	Price

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