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Dependence of cytotoxicity of menadione and cytoprotection by antioxidants in human endothelial cells on oxygen levels: Atmospheric oxygen versus physiological levels
Author(s) -
Rastogi Ashish,
Stavchansky Salomon,
Bowman Phillip
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1143.11
Subject(s) - cytoprotection , menadione , in vivo , glutathione , chemistry , cytotoxicity , oxidative stress , pharmacology , umbilical vein , antioxidant , reactive oxygen species , in vitro , oxygen , biochemistry , thioredoxin , biology , microbiology and biotechnology , organic chemistry , enzyme
The goal of in vitro screens of potential cytoprotective agents is to identify drugs that will be beneficial in vivo. However, in vitro screens are usually performed on cells cultured in atmospheric oxygen (AtmO2; 20.9%), which is much higher than the levels found in tissues in vivo (3–5%). The aim of this study was to evaluate the cytotoxicity and cytoprotective effects of an oxidant generating injurant (50, 60, and 70μM menadione; MD) and several antioxidants on human umbilical vein endothelial cells (HUVEC). Dose response studies demonstrated that 50μM MD reduced viability by 85% at AtmO2, but only by 20% at 3%O2. Antioxidants (N‐acetyl cysteine, gamma‐glutamyl cysteine, and glutathione) were more effective cytoprotectants at 3%O2 than AtmO2, and lower doses (5 and 50μM) were more effective at 3% O2 than AtmO2. However, all three compounds proved to be cytoprotective to HUVEC against MD‐induced oxidant stress at their highest dose of 500μM. These preliminary results indicate that the relatively high amount of oxygen in room air is a substrate for generating oxidants, and screens for cytoprotective antioxidants might be more predictive of in vivo performance if done at more physiologic levels.