Potential protective effects of NSAIDs/ASA in oxidatively stressed human lens epithelial cells and intact mouse lenses in culture.
OBJECTIVE
To study possible toxic effects of indomethacin, diclofenac, and celecoxib (NSAIDs) and acetylsalicylic acid (ASA) as well as potentially protective effects of these substances in oxidatively stressed human lens epithelial cells (HLEC) and in intact mouse lenses in culture.


METHODS
HLEC and mouse lenses were incubated with NSAIDs or ASA alone or in the presence of H2O2. To study apoptosis the cells were then either stained with Hoechst 33342 or assayed for caspase-3 activity. Mouse lenses were studied with respect to lens transparency.


RESULTS
Low concentrations of NSAIDs/ASA caused a significant protection against H2O2-induced apoptosis in HLEC whereas higher concentrations were toxic.


CONCLUSIONS
The protective effects of NSAIDs/ASA against oxidative damage are confined to a relatively small therapeutic window.
Petersen
A
A
Institute of Anatomy and Cell Biology, Section of Ophthalmology, Göteborg, Sweden. Anne.Petersen@anatcell.gu.se
Zetterberg
M
M
Sjöstrand
J
J
Pålsson
A Z
AZ
Karlsson
J-O
JO
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D001562:Benzimidazoles / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002386:Cataract / Q000139:chemically induced / Q000517:prevention & control*; D000068579:Celecoxib; D018929:Cell Culture Techniques; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007213:Indomethacin / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D005456:Fluorescent Dyes; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D000068579:Celecoxib; C017807:bisbenzimide ethoxide trihydrochloride; D001241:Aspirin; D007213:Indomethacin