Elsevier

Neuroscience Letters

Volume 290, Issue 3, 1 September 2000, Pages 197-200
Neuroscience Letters

Bis(7)-tacrine, a promising anti-Alzheimer's agent, reduces hydrogen peroxide-induced injury in rat pheochromocytoma cells: comparison with tacrine

https://doi.org/10.1016/S0304-3940(00)01357-4Get rights and content

Abstract

The present study investigates the effects of bis(7)-tacrine, a novel dimeric acetylcholinesterase inhibitor, on hydrogen peroxide(H2O2)-induced cell injury with comparison to the corresponding monomer, tacrine. Exposure of rat pheochromocytoma line PC12 cells to H2O2 induced significant cell damage. This reagent also caused redox desequilibrium as indicated by a decrease in activities of intracellular antioxidant enzymes such as glutathione peroxidase as well as catalase and an accumulation of malondialdehyde, a product of lipid peroxidation. Pretreatment of cells with bis(7)-tacrine or tacrine attenuated H2O2-induced cell toxicity, and bis(7)-tacrine demonstrated higher potency than tacrine in improving redox desequilibrium. These results suggest that bis(7)-tacrine and tacrine significantly protect against H2O2 insult, which might be beneficial for their potential usage in the prevention and treatment of Alzheimer's disease.

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Acknowledgements

This research is supported by grants from the Research Grant Council (HKUST 6156/97M and 6236 199M), Hong Kong, and the Biotechnology Research Institute, The Hong Kong University of Science & Technology, China. The authors are most grateful to Professor Xi Can Tang for valuable comments on the manuscript and Dr Rui Wang for technical aid.

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