Acute toxicity of propylene glycol: an assessment using cultured proximal tubule cells of human origin.
The present study assess the acute toxicity of propylene glycol (propane-1,2-diol, PD) using cultured human proximal tubule (HPT) cells as the model. Confluent monolayers of HPT cells were treated with 0-263 mM (0-2%) isotonic solutions of racemic, sinister, and rectus PD (rac-, S-, and R-PD, synonym: DL-, L-, and D-PD, respectively). Release of lactate dehydrogenase (LDH) and of preloaded 51Cr as markers of in vitro toxicity, were increased by PD in a time- and concentration-related manner, suggesting significant PD-induced damage of the HPT cell membrane. These toxic effects reached an apparent maximum within 2 hr. Further studies were performed to determine whether adverse effects of PD may occur prior to development of membrane damage. Because significant membrane damage was not apparent during the first 15 min of PD exposure, cellular release of lactate and accumulation of glucose were studied after preincubating cells in PD (treated) or pH 7.4 buffer (control) for 10 min. PD significantly increased the subsequent release of lactate by concentration- and enantiomer-dependent mechanisms with R-PD being the most potent agent. PD also inhibited the Na(+)-independent, carrier-mediated glucose accumulation without significant effects on the Na(+)-dependent pathway. These data suggest a rapid onset of cellular toxicity even when the plasma membrane integrity and viability remained apparently normal. The present studies show significant toxic effects of PD and suggest that a primary culture of HPT cells may be useful in evaluating the toxicity of xenobiotics.
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130.
K M
KM
Morshed
S K
SK
Jain
K E
KE
McMartin
D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000633:toxicity*; D013237:Stereoisomerism; D018675:Toxicity Tests / Q000379:methods
D007773:Lactates; D011409:Propylene Glycols; D002857:Chromium; D019344:Lactic Acid; D019946:Propylene Glycol; D007770:L-Lactate Dehydrogenase; D005947:Glucose