Document Detail

Inhibition of apoptosis in human retinal pigment epithelial cells treated with benzo(e)pyrene, a toxic component of cigarette smoke.
MedLine Citation:
PMID:  19959636     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To study the inhibitory effects of some agents or drugs (inhibitors) on benzo(e)pyrene (B(e)P)-induced cell death and apoptosis on human retinal pigment epithelial (ARPE-19) cells in vitro.
METHODS: ARPE-19 cells were pretreated with varying concentrations of different classes of inhibitors (calpain, benzyl isothiocyanate [BITC], simvastatin, epicatechin, genistein, resveratrol, and memantine) before B(e)P exposure. Cell viability (CV) was determined by a trypan blue dye-exclusion assay. Caspase-3/7 and caspase-9 activities were measured by fluorochrome assays. The production of reactive oxygen/nitrogen species (ROS/RNS) was measured with 2',7'-dicholorodihydrofluorescein diacetate dye assay.
RESULTS: At 30-microM concentrations, the genistein, resveratrol, and memantine inhibitors were able to reverse significantly the loss of cell viability, the activation of caspase-3/7 and caspase-9, and the production of ROS/RNS in ARPE-19 cell cultures. Memantine was the most potent and genistein was the least effective inhibitor in blocking the B(e)P-induced effects. Calpain, BITC, simvastatin, and epicatechin did not reverse the loss of cell viability in B(e)P-treated ARPE-19 cells. As a matter of fact, at the concentrations studied (15, 30, 45 microM), the BITC plus B(e)P-treated cultures showed significantly lower cell viability than the B(e)P-treated culture alone, suggesting BITC-related toxicity.
CONCLUSIONS: Genistein, resveratrol, and memantine can reverse the apoptosis and oxidant production generated by B(e)P, a toxic element of smoking. These inhibitors may be beneficial against retinal diseases associated with the loss of RPE cells.
Saffar Mansoor; Navin Gupta; A Jayaprakash Patil; Maria Fernanda Estrago-Franco; Claudio Ramirez; Rafael Migon; Ashish Sapkal; Baruch D Kuppermann; M Cristina Kenney
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-03
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  51     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-03     Completed Date:  2010-05-19     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2601-7     Citation Subset:  IM    
Department of Ophthalmology, School of Medicine, University of California, Irvine, CA 92868, USA.
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MeSH Terms
Apoptosis / drug effects*
Benzopyrenes / toxicity*
Caspase 3 / metabolism
Caspase 7 / metabolism
Caspase 9 / metabolism
Cell Line
Cell Survival / drug effects
Genistein / pharmacology*
Memantine / pharmacology*
Reactive Nitrogen Species / metabolism
Reactive Oxygen Species / metabolism
Retinal Pigment Epithelium / drug effects*,  metabolism,  pathology
Stilbenes / pharmacology*
Reg. No./Substance:
0/Benzopyrenes; 0/Reactive Nitrogen Species; 0/Reactive Oxygen Species; 0/Stilbenes; 19982-08-2/Memantine; 446-72-0/Genistein; 63APT6398R/benzo(e)pyrene; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7; EC 3.4.22.-/Caspase 9; Q369O8926L/resveratrol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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