title: Kinetics of paraquat in the isolated rat lung: Influence of sodium depletion.
abstract: Paraquat accumulates in the lung through a characteristic polyamine uptake system. It has been previously shown that paraquat uptake can be significantly prevented if extracellular sodium (Na+) is reduced, although the available data correspond to experiments performed using tissue slices or incubated cells. This type of in vitro study fails to give information on the actual behaviour occurring in vivo since the anatomy and physiology of the studied tissue is disrupted. Accordingly, the aim of the present study was to explore the usefulness of the isolated rat lung model when applied to characterize the kinetic behaviour of paraquat in this tissue after bolus injection under standard experimental conditions as well as to evaluate the influence of iso-osmotic replacement of Na+ by lithium (Li+) in the perfusion medium. The obtained results show that the present isolated rat lung model is useful for the analysis of paraquat toxicokinetics, which is reported herein for the first time. It was also observed that Na+ depletion in the perfusion medium leads to a decreased uptake of paraquat in the isolated rat lung, although it seems that this condition does not contribute to improve the elimination of paraquat once the herbicide reaches the extravascular structures of the tissue, since the paraquat tissue wash-out phase is similar under both experimental conditions assayed.
authors.affiliation: Department of Toxicology, University of Porto, REQUIMTE, Porto, Portugal.
authors.forename: R J
authors.initials: RJ
authors.lastname: Dinis-Oliveira
authors.forename: M J
authors.initials: MJ
authors.lastname: De Jesús Valle
authors.forename: M L
authors.initials: ML
authors.lastname: Bastos
authors.forename: F
authors.initials: F
authors.lastname: Carvalho
authors.forename: A
authors.initials: A
authors.lastname: Sánchez Navarro
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D018020:Lithium Compounds / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D008954:Models, Biological; D015394:Molecular Structure; D009995:Osmosis; D010269:Paraquat / Q000493:pharmacokinetics* / Q000633:toxicity; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology
chemical_list: D018020:Lithium Compounds; D012964:Sodium; D010269:Paraquat