Toxicity of ferric oxide and benzo[a]pyrene alone or in combination in respiratory tract of Sprague Dawley rats.
The association of small quantities of ferric oxide with Benzo[a]Pyrene (BaP) appears to increase in vivo the toxic effect of BaP. The effect of Fe2O3 may be mediated by the recruitment of alveolar macrophages. These cells would contribute to the production of toxic and carcinogenic BaP metabolites and would stimulate development of tumors by producing cellular mediators of inflammation. In order to understand the mechanism of the synergic effect, we have instillated male Sprague Dawley rats 3 weeks of age with a single dose: Fe2O3 (3 mg) or BaP (3 mg)/combination Fe2O3-BaP (3 mg-3 mg) in 200 microliters of physiological saline solution. Control group of identical size (treated with physiological saline solutions and untreated) were used for this study. Animals were sacrificed 48 hours after instillation and a bronchoalveolar lavage (BAL) was performed. With each BAL we have obtained protein measurement, cells were stained with May-Grünwald-Giemsa method and slides were studied with polarised light. The malonaldehyde (MDA) was measured by High Performance Liquid Chromatography. The PMN elastase determination was performed by IMAC (immuno-activation) technology. An automated kinetic method for measuring cathepsins B and L was carried out using a fluorogenic substrate: Z-Phe-Arg-AMC, a specific inhibitor E64 and AMC as an internal standard. After a quantitative Dot-Blot of the samples of BAL, an immunodetection of alpha(1)-antitrypsin (alpha(1)AT) was performed. The inhibitory capacity of alpha(1)AT was determined by an enzymatic reaction with porcine pancreatic elastase. We have observed an increased MDA level for rats intoxicated with Fe2O3 (123%), BaP (31%) and Fe2O3 + BaP (56%). The levels of PMN elastase and cathepsin B and L were increased: Fe2O3 (51-58%), BaP (52-27%). This effect was not seen for rats intoxicated by Fe2O3 + BaP. The free alpha(1)AT was decreased with the three toxics (Fe2O3: 44%--BaP: 42%--Fe2O3: 41%). The inhibitory capacity of alpha(1)AT was lower in groups of rats instilled with toxics.
Gosset
P
P
GIP-CERESTE Institute of Occupational Medicine, Lille, France.
Shirali
P
P
Marez
T
T
Boutin
A C
AC
Balduyck
M
M
Huet
G
G
Venembre
P
P
Haguenoer
J M
JM
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid; D004347:Drug Interactions; D005290:Ferric Compounds / Q000633:toxicity*; D019272:Leukocyte Elastase / Q000032:analysis; D015227:Lipid Peroxidation; D008297:Male; D011650:Pulmonary Alveoli / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000187:drug effects*
D005290:Ferric Compounds; C000499:ferric oxide; D016718:Arachidonic Acid; D001564:Benzo(a)pyrene; D019272:Leukocyte Elastase