Cellular Specific Toxicity in the Lung

Smith, Lewis L.; Nemery, Benoît

doi:10.1007/978-1-349-08759-4_1

Cited by 4 publications

(2 citation statements)

References 87 publications

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“…The cellular toxicity of paraquat has been reviewed by Smith and Nemery (147,148), Smith (146), and Lewis and Nemery (77). In brief, the cellular toxicity of paraquat is due to its cyclic reduction-oxidation: paraquat is reduced enzymatically, mainly by NADPHcytochrome P-450 reductase but also by xanthine oxidase (128), to form a paraquat monocation free radical that is rapidly reoxidized in the presence of oxygen, thus resulting in the generation of the superoxide radical.…”

Section: Polyamine Uptake In Pulmonary Epitheliummentioning

confidence: 99%

Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions

Hoet

Nemery

2000

American Journal of Physiology-Lung Cellular and Molecular Phys

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104

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The natural polyamines putrescine, cadaverine, spermidine, and spermine are found in all cells. These (poly)cations exert interactions with anions, e.g., DNA and RNA. This feature represents their best-known direct physiological role in cellular functions: cell growth, division, and differentiation. The lung and, more specifically, alveolar epithelial cells appear to be endowed with a much higher polyamine uptake system than any other major organ. In the lung, the active accumulation of natural polyamines in the epithelium has been studied in various mammalian species including rat, hamster, rabbit, and human. The kinetic parameters (Michaelis-Menten constant and maximal uptake) of the uptake system are the same order of magnitude regardless of the polyamine or species studied and the in vitro system used. Also, other pulmonary cells accumulate polyamines but never to the same extent as the epithelium. Although different uptake systems exist for putrescine, spermidine, and spermine in the lung, neither the nature of the carrier protein nor the reason for its existence is known. Some pulmonary toxicological and/or pathological conditions have been related to polyamine metabolism and/or polyamine content in the lung. Polyamines possess an important intrinsic toxicity. From in vitro studies with nonpulmonary cells, it has been shown that spermidine and spermine can be metabolized to hydrogen peroxide, ammonium, and acrolein, which can all cause cellular toxicity. In hyperoxia or after ozone exposure, the increased polyamine synthesis and polyamine content of the rat lung is correlated with survival of the animals. Pulmonary hypertension induced by monocrotaline or hypoxia has also been linked to the increased polyamine metabolism and polyamine content of the lung. In a small number of studies, it has been shown that polyamines can contribute to the suppression of immunologic reactions in the lung.

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Section: Polyamine Uptake In Pulmonary Epitheliummentioning

confidence: 99%

Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions

Hoet

Nemery

2000

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

104

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“…10 The cellular mechanisms of toxicity of paraquat have been reviewed extensively. 2,11,12 In brief, the toxicity of paraquat is probably due to a cyclic oxidation-reduction process, whereby paraquat is reduced by NADPH-cytochrome c (P450-dependent) reductase (and possibly also by xanthine oxidase 13) to form a paraquat radical which is reoxidized in the presence of oxygen (Oz),14 with the generation of the superoxide anion. This can lead to a cascade of toxic O2 species (H202, HO°) and, when the cellular reductive capacity is exhausted, membrane damage through lipid peroxidation will occur.…”

Section: Introductionmentioning

confidence: 99%

Effects of oxygen pressure and medium volume on the toxicity of paraquat in rat and human type II pneumocytes

1997

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The herbicide, paraquat is highly toxic for mammals, with the lungs being the main target organ, because of the active accumulation of the compound in this organ. The cellular toxicity of paraquat has been shown to be an O2-driven process and hyperoxia is known to increase the lethality of paraquat. In this study we have examined the effect of various O2 concentrations on the toxicity of paraquat in rat and human type II pneumocytes in culture, and we have tested whether the thickness of the liquid layer above the cells would influence the toxicity of paraquat. Type II pneumocytes were isolated from rat or human lung tissue using trypsin digestion, Percoll density gradient centrifu gation and differential attachment. Adherent cells (day 2) were incubated for 20 h in different volumes of culture medium (thickness of liquid layer), whether or not in the presence of paraquat, in the presence of different O2 tensions. The viability of the cells was assessed by the release of LDH in the culture medium. In both rat and human type II pneumocytes the toxicity of paraquat was independent of the thickness of the liquid layer (2.5 to 10 mm height). The toxicity of paraquat in rat type II pneumocytes decreased from a TC50 value of 28 μM paraquat at 21% O2 to 107 μM at 10% O2 and increased to 12 μM and 8 μM at 60% and 85% O2, respectively. For human type II pneumocytes the TC50 values were 7 μM; 25 μM and > 1000 μM paraquat at 60%, 21% and 10% O2, respectively. In this study we have shown that the diffusion of O2 through a liquid layer does not limit the toxicity of paraquat and that, as in vivo, increasing O2 partial pressure enhances the toxicity of paraquat.

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Use of isolated lung cells in pulmonary toxicology

Nemery

Hoet

1993

Toxicology in Vitro

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Cellular Specific Toxicity in the Lung

Cited by 4 publications

References 87 publications

Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions

Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions

Effects of oxygen pressure and medium volume on the toxicity of paraquat in rat and human type II pneumocytes

Use of isolated lung cells in pulmonary toxicology

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