Propylene glycol-mediated cell injury in a primary culture of human proximal tubule cells

Propylene glycol (propane-1,2-diol; PD) is a widely used solvent for intrav enous drugs. Clinical studies have reported serious side effects, including the development of renal insufficiency in patients receiving PD as drug ve hicle. Despite such clinical reports, the data on the toxicity of PD in iso lated renal cells are limited. Using primary cultured human proximal tubule (HPT) cells as an in vitro model, we have previously shown the acute toxic effects of PD in HPT cells (Morshed et at, Fundam. Appl. Toxicol. 23, 38-4 3, 1994). Since most cases of clinical toxicity are noted after prolonged a dministration of PD, the current studies were designed to investigate the t oxicity of repeated exposure of PD in HPT cells. The onset of toxicity was determined using 10-50 mM racemic, sinister, and rectus PD (rac-, S-, and R -PD, respectively) for periods up to 6 days. Cytotoxicity was noted by decr eases in thymidine incorporation, in mitochondrial metabolic activity, and in lysosomal accumulation of neutral red. Exposure of HPT cells to 50 mM PD produced toxic responses, while at 10 mM, responses were not significantly greater than those of osmotic controls. The toxicity was caused by a PD-sp ecific mechanism and by a secondary mechanism without any enantiomeric spec ificity. The HPT cell toxicity was associated with a 35% increase in cellul ar thiobarbituric acid-reactive substances and a 20% decrease in glutathion e. These findings suggest the development of a mild, subacute toxicity in n ormally proliferating HPT cells at concentrations that could be achieved in human plasma when PD is used as a drug vehicle. (C) 1998 Society of Toxico logy.