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Doxorubicin, an RNA synthesis inhibitor, prevents vasoconstriction and inhibits aberrant expression of endothelin-1 in the cerebral vasospasm model of the rat |
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| Authors: | Mostafa M G Mima T Taniguchi T Mori K |
| Affiliation: | a Department of Biochemistry and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China b Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China c Mayo Clinic Cancer Center, Department of Pharmacology, Mayo Clinic, Rochester, MN 55905, USA |
| 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. |
| Keywords: | Bis(7)-tacrine Tacrine Acetylcholinesterase inhibitor Oxidative stress PC12 cells |
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