Neuroactive steroids protect retinal pigment epithelium against oxidative stress.
This study was undertaken to assess whether neuroactive steroids, 17beta-estradiol and dehydroepiandrosterone-sulfate, enhance survival and protect DNA of human retinal pigment epithelial cells challenged by oxidative stress, and to investigate the role of sigma1 receptors in the effects of neuroactive steroids. Retinal pigment epithelial cells were treated with various concentrations of neuroactive steroids and then exposed to hydrogen peroxide. Pretreatment with steroids resulted in significant increased viability in a dose-related manner. DNA damage induced by oxidative insult was significantly lower with steroid pretreatment. The effects of 17beta-estradiol and dehydroepiandrosterone-sulfate were antagonized by pretreatment with a sigma1 receptor antagonist. The results suggest that neuroactive steroids protect retinal cells from oxidative stress, and that this effect is mediated by sigma1 receptors.
Bucolo
Claudio
C
Department of Experimental and Clinical Pharmacology, School of Medicine, University of Catania, Catania, Italy. bucocla@unict.it
Drago
Filippo
F
Lin
Li-Ren
LR
Reddy
Venkat N
VN
D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D005029:Ethylenediamines; D013778:Tetrazolium Salts; D013844:Thiazoles; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D006861:Hydrogen Peroxide; C022616:thiazolyl blue