Acrolein toxicity: comparative in vitro study with lung slices and pneumocytes type II cell line from rats.
Toxicological effects of acrolein have been studied in precision-cut rat lung slices and in L2 cells, a rat pneumocyte II cell line. These two models were cultured for 24 h with or without acrolein (0-100 microM in L2 cells; 0-200 microM in lung slices). Treatment with this pneumotoxicant produced a concentration dependent decrease in intracellular ATP levels. Acrolein concentrations higher than 50 microM induced ATP decrease in slices, while this decrease occurred from 10 microM acrolein in L2 cells. Detoxification marker evaluations showed that mostly the glutathione pathway was altered after acrolein treatment in both models. Intracellular glutathione (GSH) levels were drastically increased with an acrolein concentration of 10 microM. This increase was concomitant with glutathione-S-transferase (GST) and glutathione reductase (GRED) activities in L2 cells. After this strong increase, these enzymatic activities as well as GSH levels were quickly decreased. In precision-cut rat lung slices, the induction of the glutathione pathway was less clear-cut. A bell-shaped dose response curve was observed with a maximum for 5 microM acrolein for GST and GRED activities. These differences between acrolein toxic ranges could be explained by the presence of an active detoxification pathway in slices compared to its relative lack in L2 cells.
Monteil
C
C
Laboratoire de Toxicologie, U.F.R. Médecine Pharmacie de Rouen, France.
Le Prieur
E
E
Buisson
S
S
Morin
J P
JP
Guerbet
M
M
Jouany
J M
JM
D000171:Acrolein / Q000633:toxicity*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D002460:Cell Line; D002794:Choline / Q000378:metabolism; D046508:Culture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008171:Lung Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D002250:Carbon Radioisotopes; D010713:Phosphatidylcholines; D000171:Acrolein; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005980:Glutathione Reductase; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D002794:Choline