Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid.
Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the mechanisms of acrolein-induced cytotoxicity in human bronchial epithelial cells (HBE1) and the modulating effects of antioxidants were examined. Our results show that acrolein induces a cell death pathway in human bronchial epithelial cells, which retain key features of apoptosis, as indicated by phosphatidylserine (PS) externalization and DNA fragmentation. Acrolein-induced apoptosis was associated with depletion of cellular GSH and intracellular generation of oxidants. Supplementation of cells with either alpha-tocopherol or ascorbic acid was found to strongly inhibit acrolein-induced apoptosis and to prevent the increase in the generation of intracellular oxidants, although GSH depletion was unaffected. Moreover, recovery of cellular GSH levels after acrolein exposure was enhanced following either alpha-tocopherol or ascorbic acid supplementation. The intracellular generation of oxidants following acrolein exposure seems to be an important event triggering the apoptotic response in this model system.
Nardini
Mirella
M
Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione, Via Ardeatina 546, 00178, Rome, Italy. nardini@inran.it
Finkelstein
E I
EI
Reddy
S
S
Valacchi
G
G
Traber
M
M
Cross
C E
CE
van der Vliet
A
A
D000171:Acrolein / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017304:Annexin A5 / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D016877:Oxidants / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D017304:Annexin A5; D000975:Antioxidants; D005456:Fluorescent Dyes; D016877:Oxidants; D014810:Vitamin E; D000171:Acrolein; D005978:Glutathione; D016650:Fluorescein-5-isothiocyanate; D001205:Ascorbic Acid