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 lu ng 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 mu M in L2 cells; 0- 200 mu M in lung slices). Treatment with this pneumotoxicant produced a con centration dependent decrease in intracellular ATP levels. Acrolein concent rations higher than 50 mu M induced ATP decrease in slices, while this decr ease occurred from 10 mu M acrolein in L2 cells. Detoxification marker eval uations showed that mostly the glutathione pathway was altered after acrole in treatment in both models. Intracellular glutathione (GSH) levels were dr astically increased with an acrolein concentration of 10 mu M. This increas e was concomitant with glutathione-S-transferase (GST) and glutathione redu ctase (GRED) activities in L2 cells. After this strong increase, these enzy matic activities as well as GSH levels were quickly decreased. In precision -cut rat lung slices, the induction of the glutathione pathway was less cle ar-cut. A bell-shaped dose response curve was observed with a maximum for 5 mu M acrolein for GST and GRED activities. These differences between acrol ein toxic ranges could be explained by the presence of an active detoxifica tion pathway in slices compared to its relative lack in L2 cells. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.