Paraquat accumulation: Tissue and species specificity

Rose, Michael S.; Lock, Edward A.; Smith, Lewis L.; Wyatt, I. J.

doi:10.1016/0006-2952(76)90344-0

Cited by 193 publications

(48 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This selective accumulation, in part, explained the selective toxicity of paraquat to the lung, since it was this organ that achieved the highest concentrations of paraquat after oral dosing (8). The only exception is the kidney that was found to contain high concentrations (8), since it is the route of excretion of paraquat. However, the disposition of paraquat in the kidney is a result of glomerular filtration, rather than a selective accumulation as seen in the lung.…”

Section: Introductionmentioning

confidence: 97%

“…In no other organ studied was this timedependent accumulation ofparaquat seen (8). This selective accumulation, in part, explained the selective toxicity of paraquat to the lung, since it was this organ that achieved the highest concentrations of paraquat after oral dosing (8). The only exception is the kidney that was found to contain high concentrations (8), since it is the route of excretion of paraquat.…”

Section: Introductionmentioning

confidence: 98%

“…1). In no other organ studied was this timedependent accumulation ofparaquat seen (8). This selective accumulation, in part, explained the selective toxicity of paraquat to the lung, since it was this organ that achieved the highest concentrations of paraquat after oral dosing (8).…”

Section: Introductionmentioning

confidence: 98%

“…Consequently, it is possible to derive an apparent Km of 70 uM and a Vmax of 300 nmole paraquat/g lung hr (9). The (8). However, the uptake of paraquat into the brain only occurs in vitro, since there is no retention or accumulation of paraquat in the brain, invivo (8).…”

Section: Introductionmentioning

confidence: 99%

“…The (8). However, the uptake of paraquat into the brain only occurs in vitro, since there is no retention or accumulation of paraquat in the brain, invivo (8). This difference is likely to be due to the blood-brain barrier that prevents accumulation in vivo but would not be relevant to in vitro studies.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Importance of Epithelial Uptake Systems in Lung Toxicity

Smith¹,

Lewis²,

Wyatt³

et al. 1990

Environmental Health Perspectives

Self Cite

View full text Add to dashboard Cite

The discovery that the herbicide paraquat was selectively accumulated by the lung, both in vivo and in vitro, in comparison with other tissues, provided an explanation for its selective toxicity to the lung. This uptake process is energy dependent and obeys saturation kinetics. A characterization ofthe process led to the identification of endogenous chemicals that are the natural substrates for the system. Among these are a series of diamines and polyamines, as well as the diaminodisulfide cystamine. It appears that paraquat, because of specific structural similarities to these endogenous polyamines, is mistakenly accumulated by the lung. This uptake process is specifically located in the alveolar Type II cell, the Clara cell, and probably the alveolar Type I cell.With the development of knowledge of the structural requirements of chemicals to be accumulated by this system, it is possible to predict which chemicals will be accumulated by the lung or design molecules that are targeted to the alveolar epithelial and Clara cells.In the wider perspective, this polyamine uptake system has been found on a number of cancerous cells or tissues. With the knowledge of the uptake system in the lung, it should be possible to design drugs that will be specifically concentrated in cells that possess this system. IntroductionBecause the lung is responsible for all gas exchange necessary for oxidative metabolism, it is inevitably exposed to toxic gases, vapors, and particles (if small enough) present in the atmosphere. The respiratory function of the lung requires a large surface area (in man, about the size of a tennis court) that, on the air side, is covered by epithelial cells intimately associated with an extensive capillary network. Apart from inhalation, the lung is also exposed to toxic compounds that have been absorbed into the bloodstream or are in the form of metabolites, formed either in the lung or in extrapulmonary tissue.In order to meet its respiratory function, the lung requires numerous cell types. More than 40 cell types have been identified in the lung (1); these are required to provide the diverse architecture associated with cartilage, smooth muscle, connective tissue, submucosal glands, the vascular system, and the respiratory unit (alveoli)

show abstract

Section: Introductionmentioning

confidence: 97%