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 μM in L2 cells; 0–200 μM in lung slices). Treatment with this pneumotoxicant produced a concent...
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Published in | Toxicology (Amsterdam) Vol. 133; no. 2; pp. 129 - 138 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Ireland Ltd
15.04.1999
Amsterdam Elsevier Science |
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Abstract | 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 μM in L2 cells; 0–200 μM in lung slices). Treatment with this pneumotoxicant produced a concentration dependent decrease in intracellular ATP levels. Acrolein concentrations higher than 50 μM induced ATP decrease in slices, while this decrease occurred from 10 μM 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 μM. 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 μM 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. |
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AbstractList | 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 mu M in L2 cells; 0-200 mu M in lung slices). Treatment with this pneumotoxicant produced a concentration dependent decrease in intracellular ATP levels. Acrolein concentrations higher than 50 mu M induced ATP decrease in slices, while this decrease occurred from 10 mu M 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 mu M. 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 mu M 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. 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 μM in L2 cells; 0–200 μM in lung slices). Treatment with this pneumotoxicant produced a concentration dependent decrease in intracellular ATP levels. Acrolein concentrations higher than 50 μM induced ATP decrease in slices, while this decrease occurred from 10 μM 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 μM. 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 μM 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. 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. Acrolein toxicity was compared using precision-cut rat lung slices and L2 cells, which is a rat lung epithelial cell line that has preserved an inducible phase II metabolism. The role of glutathione and associated enzymes was examined in terms of cytotoxicity induced by acrolein in vitro. Results showed that exposure to 10 mu M acrolein for 24 h caused a marked decrease in adenosine triphosphate content in the L2 cells, which was less marked in the lung slices. Lactate dehydrogenase release was not detected in the lung slices. Initially, the total glutathione content was increased markedly in both models by exposure to acrolein, with a concomitant increase in glutathione-S-transferase and glutathione reductase activities in the L2 cells. The differences between the models were attributed to the presence of an active detoxification pathway in the lung slices that was not as effective in the L2 cells. |
Author | Buisson, S Guerbet, M Morin, J.P Le Prieur, E Monteil, C Jouany, J.M |
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Keywords | GGT, gamma glutamyl transpeptidase Pneumocytes II Toxicity in vitro LDH, lactate dehydrogenase GSH, total glutathione Acrolein GRED, glutathione reductase GPX, glutathione peroxidase GST, glutathione- S-transferase Phase II metabolism Rat lung slices ATP, adenosine triphosphate Glutathione Alveolar type II cell Rat Respiratory disease Toxicity Lung Rodentia Detoxication In vitro Histological section Vertebrata Mammalia Investigation method Animal Established cell line |
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Snippet | 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... Acrolein toxicity was compared using precision-cut rat lung slices and L2 cells, which is a rat lung epithelial cell line that has preserved an inducible phase... |
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SubjectTerms | Acrolein Acrolein - toxicity Adenosine Triphosphate - metabolism Animals Biological and medical sciences Carbon Radioisotopes Cell Line Chemical and industrial products toxicology. Toxic occupational diseases Choline - metabolism Culture Techniques Epithelial Cells - drug effects Epithelial Cells - enzymology Female gamma-Glutamyltransferase - metabolism Glutathione Glutathione - metabolism Glutathione Reductase - metabolism L-Lactate Dehydrogenase - metabolism Lung - cytology Lung - drug effects Lung - enzymology Lung Diseases - chemically induced Lung Diseases - enzymology Lung Diseases - metabolism Medical sciences Phase II metabolism Phosphatidylcholines - biosynthesis Pneumocytes II Rat lung slices Rats Rats, Wistar Toxicity in vitro Toxicology Various organic compounds |
Title | Acrolein toxicity: comparative in vitro study with lung slices and pneumocytes type II cell line from rats |
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