Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course.
OBJECTIVE
A growing evidence in the scientific literature suggests that oxidative damage plays a pathogenic role in primary open-angle glaucoma. Therefore, it is of interest to test whether drugs effective against glaucoma display antioxidant activity. We test the hypothesis that the classic beta-blocker therapy for glaucoma with timolol involves the activation of antioxidant protective mechanisms towards endothelial cells.


METHODS
Oxidative stress was induced in cultured human endothelial cells by iron/ascorbate with or without timolol pretreatment. Analysed parameters included cell viability (neutral red uptake and tetrazolium salt tests), lipid peroxidation (thiobarbituric reactive substances), and occurrence of molecular oxidative damage to DNA (8-hydroxy-2'-deoxyguanosine).


RESULTS
Oxidative stress decreased 1.8-fold cell viability, increased 3.0-fold lipid peroxidation and 64-fold oxidative damage to DNA. In the presence of timolol, oxidative stress did not modify cell viability, whereas lipid peroxidation was increased 1.3-fold, and DNA oxidative damage 3.6-fold only.


CONCLUSIONS
The obtained results indicate that timolol exerts a direct antioxidant activity protecting human endothelial cells from oxidative stress. These cells employ mechanisms similar to those observed in the vascular endothelium. It is hypothesized that this antioxidant activity is involved in the therapeutic effect of this drug against glaucoma.
Izzotti
A
A
Department of Health Sciences, University of Genoa, Italy.
Saccà
S C
SC
Di Marco
B
B
Penco
S
S
Bassi
A M
AM
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects / Q000378:metabolism; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005902:Glaucoma, Open-Angle / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D013999:Timolol / Q000494:pharmacology*
D000959:Antihypertensive Agents; D013999:Timolol