Abstract | BACKGROUND: METHODS: We investigated the hypothesis that apoptosis plays a critical role in lung injury and down-regulation of CYP1A1 induction in mixed exposures to CD and PAHs. We exposed rats intratracheally to 0.0, 2.5, 10.0, 20.0, or 40.0 mg/rat CD and, 11 days later, to intraperitoneal beta-naphthoflavone (BNF) , a PAH. In another group of rats exposed to CD and BNF, caspase activity was inhibited by injection of the pan- caspase inhibitor Q-VD-OPH [ quinoline-Val-Asp (OMe) -CH2-OPH]. RESULTS: In rats exposed to BNF, CD exposure increased alveolar expression of the proapoptotic mediator Bax but decreased CYP1A1 induction relative to BNF exposure alone. Pan- caspase inhibition decreased CD-associated Bax expression and apoptosis but did not restore CYP1A1 activity. Further, CD-induced lung inflammation and alveolar epithelial cell hypertrophy and hyperplasia were not suppressed by caspase inhibition. CONCLUSIONS: Combined BNF and CD exposure increased Bax expression and apoptosis in the lung, but Bax and apoptosis were not the major determinants of early lung injury in this model.
|
Authors | Mohamed M Ghanem, Lori A Battelli, Robert R Mercer, James F Scabilloni, Michael L Kashon, Jane Y C Ma, Joginder Nath, Ann F Hubbs |
Journal | Environmental health perspectives
(Environ Health Perspect)
Vol. 114
Issue 9
Pg. 1367-73
(Sep 2006)
ISSN: 0091-6765 [Print] United States |
PMID | 16966090
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Caspase Inhibitors
- Coal
- Dust
- Polycyclic Aromatic Hydrocarbons
- beta-Naphthoflavone
- Aryl Hydrocarbon Hydroxylases
- Cyp1b1 protein, rat
- Cytochrome P-450 CYP1A1
- Cytochrome P-450 CYP1B1
- Caspases
|
Topics |
- Animals
- Apoptosis
(drug effects, physiology)
- Aryl Hydrocarbon Hydroxylases
(metabolism)
- Caspase Inhibitors
- Caspases
(metabolism)
- Coal
(toxicity)
- Cytochrome P-450 CYP1A1
(metabolism)
- Cytochrome P-450 CYP1B1
- Dose-Response Relationship, Drug
- Dust
- Gene Expression Regulation
(drug effects)
- Lung
(drug effects, pathology)
- Male
- Pneumonia
(chemically induced)
- Polycyclic Aromatic Hydrocarbons
(toxicity)
- Pulmonary Alveoli
(cytology, metabolism)
- Rats
- Rats, Sprague-Dawley
- beta-Naphthoflavone
(toxicity)
|