title: Modification of the proteinase/anti-proteinase balance in the respiratory tract of Sprague-Dawley rats after single intratracheal instillation of benzo[A]pyrene-coated onto Fe(2)O(3) particles.
abstract: Available data suggest that repeated concurrent exposure to haematite (Fe(2)O(3)) and benzo[A]pyrene (B[A]P) results in a decreased latency and an increased incidence of lung tumours in rodents compared to exposure to B[A]P alone. Moreover, the reactive oxygen species (ROS) formed by the lung cells themselves and/or by activated inflammatory cells may possibly contribute to the development of pulmonary disorders such as cancer formation. In order to investigate the precise role of iron in the injury induced by B[A]P-coated onto Fe(2)O(3) particles, we tend to address the hypothesis that Fe(2)O(3) and B[A]P, alone or in association, can induce oxidative stress conditions (malondialdehyde) and/or inflammatory reactions (interleukin-6) and thereby disrupt the proteinase/anti-proteinase balance (cathepsins B and L, polynuclear neutrophil (PNN) elastase, alpha-1 proteinase inhibitor (alpha(1)PI) and its inhibitory capacity) in the rat respiratory tract. Thus, Fe(2)O(3) or B[A]P-coated onto Fe(2)O(3) particles produce oxidative stress conditions through not only iron-catalysed oxidative reactions but also inflammatory processes. However, B[A]P initiates only inflammatory responses. These pollutants generate increased levels of proteases and decrease the concentrations of free alpha(1)PI. There is also a clear relationship between the partial inactivation of alpha(1)PI and the occurrence of ROS after exposure to Fe(2)O(3), alone or as a carrier of B[A]P. Hence, the proteinase/anti-proteinase balance might be more disrupted by Fe(2)O(3) or B[A]P-coated onto Fe(2)O(3) particles than by B[A]P alone. These results suggest a mechanism that can explain why B[A]P-coated onto Fe(2)O(3) particles are more injurious than B[A]P alone.
authors.affiliation: GIP-CERESTE, Laboratoire Universitaire de Médecine du Travail et des Risques Professionnels, Faculté de Médecine, Pôle Recherche, 01 place de Verdun, 59045 Lille Cedex, France.
authors.forename: G
authors.initials: G
authors.lastname: Garçon
authors.forename: J
authors.initials: J
authors.lastname: Campion
authors.forename: M H
authors.initials: MH
authors.lastname: Hannothiaux
authors.forename: A C
authors.initials: AC
authors.lastname: Boutin
authors.forename: P
authors.initials: P
authors.lastname: Venembre
authors.forename: M
authors.initials: M
authors.lastname: Balduyck
authors.forename: J M
authors.initials: JM
authors.lastname: Haguenoer
authors.forename: P
authors.initials: P
authors.lastname: Shirali
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism*; D005290:Ferric Compounds / Q000633:toxicity*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D010196:Pancreatic Elastase / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D015850:Interleukin-6; D009153:Mutagens; D011480:Protease Inhibitors; D017382:Reactive Oxygen Species; C000499:ferric oxide; D001564:Benzo(a)pyrene; D008315:Malondialdehyde; D002403:Cathepsins; D010450:Endopeptidases; D010196:Pancreatic Elastase; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat