Diprivan attenuates the cytotoxicity of nitric oxide in cultured human bronchial epithelial cells.
OBJECTIVE
Excess nitric oxide (NO) and its reactive derivatives cause oxidative reactions that lead to cell death. Propofol, an intravenous anesthetic, exhibits antioxidant properties. Diprivan is a widely used commercial preparation of propofol that is emulsified in 10% intralipids. We sought to test the hypothesis that clinically encountered concentrations of Diprivan attenuate the toxicity of NO in a cell culture model.


METHODS
Prospective, randomized, controlled trial.


METHODS
University research laboratory.


METHODS
Cultured human bronchial epithelial (IB-3) cells.


METHODS
Human bronchial epithelial cell cultures were randomly assigned to one of the following six groups: no additives (negative control), NO alone (positive control), NO with either 1 micro M, 10 micro M or 100 micro M Diprivan, and 100 micro M Diprivan alone (Diprivan control). S-nitroso-N-acetylpenicillamine (SNAP) was used to generate NO.


RESULTS
Hemacytometry with trypan blue staining was used to measure cell survival. To assess direct NO toxicity, immunoblot assays for nitrotyrosine-containing proteins in cell homogenates were performed. Exogenous NO significantly decreased live cell numbers and increased intracellular nitrotyrosine-containing protein concentrations (p<0.001). Diprivan significantly attenuated these changes in a concentration-independent manner (p<0.001). At concentrations as low as 1 micro M, Diprivan exhibited cytoprotective effects.


CONCLUSIONS
Diprivan effectively attenuates the cytotoxicity of excessive NO exposure in IB-3 cells at concentrations that are clinically attainable.
Huang
Chun Jen
CJ
Department of Pediatrics, College of Medicine University of Florida, P.O. Box 100296 JHMHC, 1600 SW Archer Road, Gainesville, FL 32610, USA.
Slovin
Paul N
PN
Nielsen
Richard B
RB
Skimming
Jeffrey W
JW
D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002461:Cell Line, Transformed; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000633:toxicity*; D015742:Propofol / Q000494:pharmacology*; D011446:Prospective Studies
D009569:Nitric Oxide; D015742:Propofol