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.

Effect of transforming growth factor-β1 on acute lung injury caused by paraquat

“…Paraquat accumulates in the lung through a characteristic polyamine uptake system. Several studies have been undertaken with regard to paraquat as a useful tool for the exploration of the early pathogenesis of pulmonary injury (20).…”

Pyrrolidine Dithiocarbamate Attenuates Paraquat‐Induced Lung Injury in Rats

“…It has been extensively demonstrated that it is highly toxic to multiorgans when absorbed through ingestion, skin contact, or inhalation. The primary target organ for PQ toxicity is the lung as a consequence of its accumulation, against a concentration gradient, through the highly developed polyamine uptake system [1–3]. The toxicity mechanism of PQ is mainly due to a sustained redox-cycling effect, resulting in oxidative stress-related insults such as lipid peroxidation.…”

Continuous hypoxia attenuates paraquat-induced cytotoxicity in the human A549 lung carcinoma cell line

“…The lung is considered the primary target organ for PQ toxicity as a consequence of the accumulation of PQ against a concentration gradient via the highly developed polyamine-uptake system (Dinis-Oliveira et al, 2006a, 2006bChang et al, 2009). The primary effect of PQ toxicity is seen in the lungs, where PQ gets accumulated via a process of active transport in the Clara cells and alveolar type I and type II epithelial cells, leading initially to pulmonary edema, infiltration of inflammatory cells, and damage to the alveolar epithelium, and later progressing to lung fibrosis and respiratory failure (Smith and Heath, 1975;Thurlbeck and Thurlbeck, 1976;Tomita et al, 2007).…”