Pulmonary effects of paraquat in the first day after injection

Fisher, H. Kenneth; Clements, J. A.; Tierney, DF; Wright, RR

doi:10.1152/ajplegacy.1975.228.4.1217

Cited by 68 publications

(13 citation statements)

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“…The results of this study are in line with several other reports [5][6][7]15]. We confirmed the suggestion by FISHER et al [5] that intra-alveolar oedema is present within 24 h after paraquat intoxication and that this model is a model not of primary surfactant synthesis damage, but of surfactant inhibition.…”

Section: Discussionsupporting

confidence: 94%

“…We confirmed the suggestion by FISHER et al [5] that intra-alveolar oedema is present within 24 h after paraquat intoxication and that this model is a model not of primary surfactant synthesis damage, but of surfactant inhibition. The increased total protein and raised minimal surface tension at 24 h after intoxication clearly show that the properties of surfactant in the alveoli are changing.…”

Section: Discussionsupporting

confidence: 92%

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Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats

So¹,

Buijzer²,

Gommers³

et al. 1998

Eur Respir J

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Paraquat is a weed killer which causes often fatal lung damage in humans and other animals. There is evidence that the pulmonary surfactant system is involved in the pathophysiology of respiratory failure after paraquat intoxication and, therefore, the possible therapeutic effect of intratracheal surfactant administration on gas exchange in rats with progressive lung injury induced by paraquat poisoning was studied. In one group of rats, the time course of the development of lung injury due to paraquat intoxication was characterized. In a second group of rats, 72 h after paraquat intoxication, the animals underwent mechanical ventilation and only those animals in which the arterial oxygen tension/inspiratory oxygen fraction (Pa,O2/FI,O2) decreased to below 20 kPa (150 mmHg) received exogenous surfactant (200 mg x kg(-1) body weight). Within 3 days the rats in group 1 developed progressive respiratory failure, demonstrated not only by impaired gas exchange and lung mechanics but also by increased minimal surface tension and increased protein concentration in bronchoalveolar lavage fluid. In group 2, intratracheal surfactant administration increased Pa,O2/FI,O2 significantly within 5 min (14.4+/-2.4 kPa (108+/-18 mmHg)) to (55.2+/-53 kPa (414+/-40 mmHg)) and sustained this level for at least 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of severe respiratory failure caused by paraquat poisoning.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 92%

Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats

So¹,

Buijzer²,

Gommers³

et al. 1998

Eur Respir J

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“…Unlike SP-D ϩ/ϩ animals, SP-D Ϫ/Ϫ mice were able to maintain higher BAL phospholipid levels, phospholipidassociated SP-B, and surfactant function early in hyperoxic exposure. Several previous studies have shown that exposure of rodents to either prolonged periods of hyperoxia or to oxidizing agents such as paraquat to induce a relatively severe oxidative insult resulted in significant lung dysfunction that was associated with oxidative changes in endogenous surfactant (29,37,50,68) and depletion of surfactant phospholipid and surfactant proteins (35). Instillation of exogenous surfactant has been shown to attenuate the degree of alveolar injury caused by hyperoxia resulting in improved survival (51).…”

Section: Ablation Of the Sp-d Gene Results In Progressive Alveolar Prmentioning

confidence: 99%

SP-D-deficient mice are resistant to hyperoxia

Jain¹,

Atochina‐Vasserman²,

Kadire³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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surfactant protein D; inflammation; alveolar macrophages; collectin AS A BYPRODUCT OF THE USE of high oxygen (O 2 ) concentrations often required in management of patients with respiratory failure, reactive oxygen species produced during hyperoxic exposure can adversely affect the lung. It has been proposed that the balance between oxygen radical production and antioxidant capacities can modulate oxygen-mediated injury. The lung responds to hyperoxia by enhancing the expression of cytoprotective proteins including antioxidants (65), DNA repair enzymes (55), and regulators of cell survival. In addition, elevated expression of certain surfactant components occurs in lungs of adult (54) and neonatal rats (64) during adaptation to both sublethal (85%) and lethal (95%) oxygen (1).Surfactant protein D (SP-D), an airway epithelial secretory product, belongs to the superfamily of mammalian C-type (Ca 2ϩ -binding) lectins (collectins), which also includes SP-A and serum mannose-binding lectin. Like all collectins, monomeric SP-D is distinguished by the presence of an NH 2 -terminal cysteine-rich domain, a collagen domain, a coiled-coil neck domain, and a lectin domain with calcium-dependent regulatory elements. SP-D monomers associate through their collagenous domains to form a basic functional trimer, which then associates into higher order multimers. This oligomeric assembly provides high avidity, affinity, and specificity to SP-D ligand recognition. In the lung, SP-D ligands include allergens, particles, bacterial cell wall components, and viral envelope proteins (26). SP-D is also known to be chemotactic for neutrophils and mononuclear phagocytes (25) and to modulate alveolar type II (61) and macrophage function in vitro (39).SP-D is produced primarily by alveolar type II cells and nonciliated bronchiolar cells in the lung (24) and is constitutively secreted into the alveoli where it influences surfactant homeostasis (40), effector cell functions, and host defense. It is upregulated in a variety of inflammatory and infectious conditions including Pneumocystis pneumonia (5), asthma (2), and bleomycin injury (17). Mice or rats exposed to hyperoxic challenge also have increases in SP-D (13), suggesting that it may have a role in protection from this insult.Targeted disruption of the SP-D gene in vivo in two genetically different backgrounds has been shown to result in mice with increased alveolar and cellular pools of surfactant phospholipid, accelerated development of age-related emphysema, and large, foamy macrophages (14,40). These SP-D null mice (SP-D Ϫ/Ϫ ) also exhibit an increase in the baseline level of inflammation in the lung, increases in metalloproteinase activity, and biochemical evidence of enhanced oxidative-nitrative stress (4, 63). In addition, SP-D deficiency also confers susceptibility to specific bacterial (45) and viral infections (46).We have previously reported modulation of bleomycininduced lung injury by SP-D. In SP-D Ϫ/Ϫ mice, we showed increased susceptibility to bleomycin and evidence of oxida...

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“…Thus, it has been suggested that paraquatstimulated NADPH depletion may be a primary toxic event, in that this effect would be expected to perturb several important cell processess (49,71,(101)(102)(103) (102). These investigators also found that the activity of the pentosephosphate pathway was increased in lungs of rats after intravenous administration of paraquat or diquat (a closely related bipyridylium herbicide capable of redox cycling but not accumulated into lung tissue).…”

Section: Other Potential Superoxide-mediated Reactionsmentioning

confidence: 99%

Paraquat: model for oxidant-initiated toxicity.

Bus¹,

Gibson²

1984

Environ Health Perspect

507

238

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Paraquat, a quaternary ammonium bipyridyl herbicide, produces degenerative lesions in the lung after systemic administration to man and animals. The pulmonary toxicity of paraquat resembles in several ways the toxicity of several other lung toxins, including oxygen, nitrofurantoin and bleomycin. Although a definitive mechanism of toxicity of paraquat has not been delineated, a cyclic single electron reduction/oxidation of the parent molecule is a critical mechanistic event. The redox cycling of paraquat has two potentially important consequences relevant to the development of toxicity: generation of "activated oxygen" (e.g., superoxide anion, hydrogen peroxide, hydroxyl radical) which is highly reactive to cellular macromolecules; and/or oxidation of reducing equivalents (e.g., NADPH, reduced glutathione) necessary for normal cell function. Paraquat-induced pulmonary toxicity, therefore, is a potentially useful model for evaluation of oxidant mechanisms of toxicity. Furthermore, characterization of the consequences of intracellular redox cycling of xenobiotics will no doubt provide basic information regarding the role of this phenomena in the development of chemical toxicity.

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Pulmonary effects of paraquat in the first day after injection

Cited by 68 publications

References 0 publications

Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats

Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats

SP-D-deficient mice are resistant to hyperoxia

Paraquat: model for oxidant-initiated toxicity.

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