Cyclophosphamide-induced lung damage in mice: protection by a small preliminary dose

Collis, C.; Wilson, Claude; Jones, J. B.

doi:10.1038/bjc.1980.167

Cited by 43 publications

(10 citation statements)

References 15 publications

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“…Lung damage, as measured by increased ventilation rate, was significantly reduced if the priming dose (50 mg/kg) was given either 7 or 14 days before 250 mg/kg of cyclophosphamide. However, if the animals were "primed" on the day prior to the large dose of the drug, lung damage seemed to be enhanced (94 (96) and has since been confirmed in several laboratories (64,(97)(98)(99)(100)(101). Diffuse lung lesions develop after oral or intraperitoneal administration of BHT and are dose-dependent (102,103).…”

Section: Interactions Resulting From Exposures Separated In Timementioning

confidence: 92%

The role of toxicological interactions in lung injury.

Witschi¹,

Hakkinen²

1984

Environ Health Perspect

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Interactions between two or more toxic agents can produce lung damage by chemical-chemical interactions, chemical-receptor interactions or by modification, by a first agent, of the cell and tissue response to a second agent. Interactions may occur by simultaneous exposure and if exposure to the two agents is separated in time. Chemical-chemical interactions have been mostly studied in the toxicology of air pollutants, where it was shown that the untoward effect of certain oxidants may be enhanced in the presence of other aerosols. Interactions at the receptor site have been found in isolated perfused lung experiments. Oxygen tolerance may be an example, when pre-exposure to one concentration of oxygen mitigates later exposure to 100% oxygen by modifying cellular and enzymatic composition of the lung. Damage of the alveolar zone by the antioxidant butylated hydroxytoluene (BHT) can be greatly enhanced by subsequent exposure to oxygen concentration which, otherwise, would have little if any demonstrable effect. The synergistic interaction between BHT and oxygen results in a resulting interstitial pulmonary fibrosis. Acute or chronic lung disease may then be caused not only by one agent, but very likely in many instances by the interaction of several agents.

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Section: Interactions Resulting From Exposures Separated In Timementioning

confidence: 92%

The role of toxicological interactions in lung injury.

Witschi¹,

Hakkinen²

1984

Environ Health Perspect

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“…[3], Brain and co-workers [4, 5] and Collis et al [9], who used damaging agents other than acid or hyperoxia to generate lung injury. The increased LDH and albumin concentrations in the HCl-pretreated animals indicate that acid leads to gross cellular lung damage, cell lysis, altered microvascular permeability, and alveolar edema.…”

Section: Discussionmentioning

confidence: 99%

Lung Damage Aggravates Gastric Mucosal Lesions Induced by Ethanol in the Rat

et al. 1995

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The hypothesis that severe lung damage generated by acid aspiration or a 50-hour exposure to 100% oxygen aggravates ethanol-induced hemorrhagic mucosal lesions in the stomach was examined in the rat. Animals were either given intratracheally with pyrogen-free saline or HCl (pH 1.75) or exposed for 50 h to 100% oxygen before the intragastric application of 1 ml of 50 or 75% ethanol. All rats receiving 50% ethanol were also given 3% monastral blue, 3 min before ethanol administration as a vascular tracer. Lung acid damage and inflammation as assessed by bronchopulmonary lavage were severe. We observed a significant increase in extracellular lactate dehydrogenase β-glucosaminidase, albumin and the number of polymorphonuclear leukocytes in the lavage fluid. The number of resident macrophages decreased significantly. Blood gas analysis was not influenced. Hemorrhagic gastric mucosal lesions after 50 or 75% ethanol increased from 4.4 or 8.2% to 9.8 or 13.1% after HC1 and from 6.7 or 18.2% to 10.6 or 21.6% of the glandular stomach following oxygen exposure. The area of mucosal vascular damage caused by 50% ethanol as revealed by monastral blue labelling was 3.3 and 2.6 times larger in rats with lung damage induced by HC1 or hyperoxia, respectively. Thus, severe lung damage predisposes to microvascular damage and aggravates chemically induced hemorrhagic mucosal lesions.

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“…In our study, rats were injected with a 50 mg-kg"1 dose of CY, and no increase in either PW or dry lung weight was observed. High concen trations of oxygen and CY are synergistically toxic for the lung [Häkkinen et al, 1982;Morse et al, 1985;Collis et al, 1980). Thus, although CY alone might not have been responsible for the absence of edema reduction, it might have amplified the toxic effects of oxygen on the lung.…”

Section: Discussionmentioning

confidence: 99%

Acute Hyperoxic Lung Edema Is Not Reduced by Granulocyte Depletion in Rats

et al. 1988

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In order to study the role of neutrophils in hyperoxic lung edema, we induced a sustained granulocytopenia in rats by giving them a single intraperitoneal injection of 50 mg · kg”1 cyclophosphamide (CY) (CY-injected rats). Hyperoxic lung damage (FIO₂ = 1.0, 60 h) was assessed by measuring pulmonary water (PW). Exposure to hyperoxia coincided with the granulocytopenic period. After exposure to hyperoxia, the difference in PW between CY- and 0.09% saline solution-injected (S-injected) rats was not significant (PW (g) (x ± 1 SD): CY-injected rats: 1.49 ± 0.09; S-injected rats: 1.68 ± 0.09, NS). If neutrophils have a pathogenic role in hyperoxic lung injury, the absence of edema reduction in neutropenic rats could be explained by pulmonary infection, insufficient neutrophil depletion or cumulative lung toxicity of CY and oxygen. No pulmonary infectious agents could be detected in lung and bronchoalveolar lavage cultures. Although already severe, the neutrophil depletion was intensified by a second injection of CY (50 mg · kg”1). After exposure to hyperoxia, the number of neutrophils in lung lavage was much lower in these neutropenic rats (156 · 103 ± 33 · 103) than in S-injected rats (571 103 ± 100–103) (p < 0.001), but no significant reduction of PW was observed. No significant increase was observed in either PW or dry lung weight in CY-injected rats not exposed to hyperoxia. CY alone might not be responsible for the absence of edema reduction, but might amplify the toxic effects of oxygen on the lung. In conclusion, we could not demonstrate any reduction of lung edema due to granulocyte depletion. The role of neutrophils in hyperoxic lung injury has yet to be fully elucidated.

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Cyclophosphamide-induced lung damage in mice: protection by a small preliminary dose

Cited by 43 publications

References 15 publications

The role of toxicological interactions in lung injury.

The role of toxicological interactions in lung injury.

Lung Damage Aggravates Gastric Mucosal Lesions Induced by Ethanol in the Rat

Acute Hyperoxic Lung Edema Is Not Reduced by Granulocyte Depletion in Rats

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