The neuroprotective effect of ladostigil against hydrogen peroxide-mediated cytotoxicity
Weinreb, O; Bar-Am, O; Amit, T; Drigues, N; Sagi, Y; Youdim, MBH
| HERO ID | 622631 |
|---|---|
| In Press | No |
| Year | 2008 |
| Title | The neuroprotective effect of ladostigil against hydrogen peroxide-mediated cytotoxicity |
| Authors | Weinreb, O; Bar-Am, O; Amit, T; Drigues, N; Sagi, Y; Youdim, MBH |
| Journal | Chemico-Biological Interactions |
| Volume | 175 |
| Issue | 1-3 |
| Page Numbers | 318-326 |
| Abstract | Abstract: The multifunctional, anti-Alzheimer drug, ladostigil (TV3326) [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate] combines the neuroprotective effects of the anti-Parkinson drug, rasagiline, a selective monoamine oxidase (MAO)-B inhibitor, with the cholinesterase (ChE) inhibitory activity of rivastigmine in a single molecule. Ladostigil has been shown to possess potent antiapoptotic and neuroprotective activities in various oxidative insults in vitro and in vivo, such as prevention of the fall in mitochondrial membrane potential and regulation of Bcl-2 family proteins. In the present study, we demonstrate that ladostigil (1μM) increased cell viability, associated with the increase of catalase activity and decrease of intracellular reactive oxygen species (ROS) production in human SH-SY5Y neuroblastoma cells exposed to (hydrogen peroxide) H2O2. Furthermore, ladostigil significantly elevated mRNA levels of the antioxidants enzymes, catalase, NAD(P)H quinone oxidoreductase 1 (NQO1) and peroxiredoxin 1 (Prx 1) in H2O2-treated SH-SY5Y cells. Chronic treatment with ladostigil (1mg/kg gavage per day for 30 days) markedly up-regulated mRNA expression levels of various antioxidant enzymes in aged rat hippocampus (e.g. glutathione peroxidase precursor (GSHPX-P), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD)). These findings indicate that in addition to its multiple neuroprotective characteristics, ladostigil also possesses antioxidant properties, which might be beneficial for the treatment of oxidative stress (OS) in aging and age-associated neurodegenerative diseases. [Copyright 2008 Elsevier] Copyright of Chemico-Biological Interactions is the property of Elsevier Science Publishers B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts) |
| Doi | 10.1016/j.cbi.2008.05.038 |
| Pmid | 18598687 |
| Wosid | WOS:000260110500060 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-50649083041&doi=10.1016%2fj.cbi.2008.05.038&partnerID=40&md5=e6cb98c578118d2e9158b652c13e4bb9 |
| Is Public | Yes |
| Language Text | English |
| Keyword | NEUROPROTECTIVE agents; CELL-mediated cytotoxicity; MITOCHONDRIAL membranes; OXIDATIVE stress; CATALASE; HYDROGEN peroxide; PHYSIOLOGICAL aspects |
| Is Qa | No |