Bis(7)-tacrine, a promising anti-Alzheimer's agent, reduces hydrogen peroxide-induced injury in rat pheochromocytoma cells: comparison with tacrine.
The present study investigates the effects of bis(7)-tacrine, a novel dimeric acetylcholinesterase inhibitor, on hydrogen peroxide(H(2)O(2))-induced cell injury with comparison to the corresponding monomer, tacrine. Exposure of rat pheochromocytoma line PC12 cells to H(2)O(2) 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 H(2)O(2)-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 H(2)O(2) insult, which might be beneficial for their potential usage in the prevention and treatment of Alzheimer's disease.
Xiao
X Q
XQ
Department of Biochemistry and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, Kowloon, China.
Lee
N T
NT
Carlier
P R
PR
Pang
Y
Y
Han
Y F
YF
D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013619:Tacrine / Q000031:analogs & derivatives* / Q000494:pharmacology*
C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D013619:Tacrine; D006861:Hydrogen Peroxide; D000109:Acetylcholine