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 inToxicology (Amsterdam) Vol. 133; no. 2; pp. 129 - 138
Main Authors Monteil, C, Le Prieur, E, Buisson, S, Morin, J.P, Guerbet, M, Jouany, J.M
Format Journal Article
LanguageEnglish
Published Shannon 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.
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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Issue 2
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
Language English
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Elsevier Science
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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
URI https://dx.doi.org/10.1016/S0300-483X(99)00015-3
https://www.ncbi.nlm.nih.gov/pubmed/10378479
https://search.proquest.com/docview/14517855
https://search.proquest.com/docview/17265345
Volume 133
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