We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Neuroprotective effects of tempol acyl esters against retinal ganglion cell death in a rat partial optic nerve crush model.
- Authors
Thaler, Sebastian; Fiedorowicz, Michal; Grieb, Pawel; Wypych, Zbigniew; Knap, Narcyz; Borowik, Tomasz; Zawada, Katarzyna; Kaminski, Jaroslaw; Wozniak, Michal; Rejdak, Robert; Zrenner, Eberhart; Schuettauf, Frank
- Abstract
. Purpose: The aim of this study is to search for more effective derivatives of the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl). Although tempol is neuroprotective in a rat partial optic nerve crush (PONC) model, relatively high doses are required to exert this effect. Methods: Tempol acyl esters with different-length fatty acids (tempol-C4, tempol-C8, tempol-C12 and tempol-C16) were synthesized and the following properties were evaluated: water-octanol partition coefficient, liposome-liposome energy transfer, and electron paramagnetic resonance (EPR). Brown Norway rats underwent PONC and received tempol or acyl esters intraperitoneally once daily for 7 consecutive days. We then compared the effects of tempol and its four esters on retinal ganglion cell (RGC) damage using a retrograde labelling method. Results: The water-octanol partition coefficient increased with increasing length of attached acyl chain. However, the energy of the liposome-liposome transfer seemed to be optimal for tempol-C8 and tempol-C12. The EPR signal was very similar for all tested compounds, suggesting similar efficiency of superoxide scavenging. Partial optic nerve crush in vehicle-treated animals reduced RGC numbers by approx. 59% when compared with sham-operated eyes. Tempol did not affect RGC loss at a dose of 1 mg/kg. In contrast, at molar doses equivalent to 1 mg/kg of tempol, tempol-C8 showed a significant neuroprotective effect, whereas tempol-C4, tempol-C12 and tempol-C16 did not act neuroprotectively. Conclusion: Manipulating the hydrophobicity of tempol seems to be a promising tool for developing more potent neuroprotectants in the PONC degeneration model. However, the resulting compounds need further pharmacological evaluation.
- Subjects
NEUROPROTECTIVE agents; ESTERS; RETINAL ganglion cells; CELL death; OPTIC nerve
- Publication
Acta Ophthalmologica (1755375X), 2011, Vol 89, Issue 7, pe555
- ISSN
1755-375X
- Publication type
Article
- DOI
10.1111/j.1755-3768.2011.02180.x