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 dimer ic acetylcholinesterase inhibitor, on hydrogen peroxide(H2O2)-induced cell injury with comparison to the corresponding monomer, tacrine. Exposure of r at 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 pero xidase as well as catalase and an accumulation of malondialdehyde, a produc t of lipid peroxidation. Pretreatment of cells with bis(7)tacrine or tacrin e attenuated H2O2-induced cell toxicity, and bis(7)-tacrine demonstrated hi gher 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 preventi on and treatment of Alzheimer's disease. (C) 2000 Elsevier Science Ireland Ltd. Ail rights reserved.