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British Journal of Experimental Pathology logoLink to British Journal of Experimental Pathology
. 1981 Dec;62(6):643–654.

The Enhancement of Paraquat Toxicity in Rats by 85% Oxygen: Lethality and Cell-Specific Lung Damage

P L Keeling, I S Pratt, W N Aldridge, L L Smith
PMCID: PMC2041731  PMID: 7326219

Abstract

When rats were dosed s.c. with paraquat or diquat and then exposed to air or 85% oxygen, the lethality of paraquat was enhanced approximately 10-fold by 85% oxygen exposure, whereas the lethality of diquat was enhanced only 2-fold. This increase in toxicity was not caused by an increase in the lung concentration of either bipyridyl.

The lungs of rats which had been dosed with paraquat (2·5 and 20 mg/kg) or diquat (10 and 20 mg/kg) and exposed to air or 85% oxygen were examined morphologically at various times up to 24 h after dosing. By 24 h after dosing, the extent of damage appeared to be generally similar for those doses of paraquat that killed the same proportion of animals when combined with air or 85% oxygen. The combination of 20 mg paraquat/kg and air exposure caused alveolar epithelial Type I and Type II cell damage. Following 2·5 mg paraquat/kg and 85% oxygen exposure or 20 mg diquat/kg and 85% oxygen exposure the Type II alveolar epithelial cells were more severely damaged than the Type I epithelial and endothelial cells. In contrast, there was no cell damage after 1 or 2 days of exposure to 85% oxygen alone, and when lung damage did develop after 4 days of exposure, it was the capillary endothelial cells which were primarily affected. Thus the toxic effects of paraquat to the Type II alveolar epithelial cells are enhanced by exposure to oxygen.

The ability of the lung to accumulate paraquat was measured in lung slices that had been taken from rats dosed with paraquat or diquat and exposed to air or 85% oxygen for 2, 8 or 24 h. Paraquat accumulation was inhibited at times after dosing when the alveolar epithelial cells appeared to be damaged. This is consistent with the hypothesis that paraquat is primarily accumulated by the alveolar epithelial cells.

We have concluded that (i) the toxic effects of paraquat to the alveolar epithelial cells of the lung are markedly enhanced when paraquat-treated rats are exposed to 85% oxygen, and (ii) the combination of low concentrations of paraquat (2·5 mg/kg) and 85% oxygen or high concentrations of diquat (20 mg/kg) and 85% oxygen damages the Type II alveolar epithelial cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Clark D. G., Hurst E. W. The toxicity of diquat. Br J Ind Med. 1970 Jan;27(1):51–55. doi: 10.1136/oem.27.1.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clark D. G., McElligott T. F., Hurst E. W. The toxicity of paraquat. Br J Ind Med. 1966 Apr;23(2):126–132. doi: 10.1136/oem.23.2.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Daniel J. W., Gage J. C. Absorption and excretion of diquat and paraquat in rats. Br J Ind Med. 1966 Apr;23(2):133–136. doi: 10.1136/oem.23.2.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Douze J. M., Van Heijst A. N. The paraquat intoxication--oxygen a real poison. Acta Pharmacol Toxicol (Copenh) 1977;41 (Suppl 2):241–245. [PubMed] [Google Scholar]
  5. Fisher H. K., Clements J. A., Wright R. R. Enhancement of oxygen toxicity by the herbicide paraquat. Am Rev Respir Dis. 1973 Feb;107(2):246–252. doi: 10.1164/arrd.1973.107.2.246. [DOI] [PubMed] [Google Scholar]
  6. Haugaard N. Cellular mechanisms of oxygen toxicity. Physiol Rev. 1968 Apr;48(2):311–373. doi: 10.1152/physrev.1968.48.2.311. [DOI] [PubMed] [Google Scholar]
  7. Kapanci Y., Weibel E. R., Kaplan H. P., Robinson F. R. Pathogenesis and reversibility of the pulmonary lesions of oxygen toxicity in monkeys. II. Ultrastructural and morphometric studies. Lab Invest. 1969 Jan;20(1):101–118. [PubMed] [Google Scholar]
  8. Kehrer J. P., Haschek W. M., Witschi H. The influence of hyperoxia on the acute toxicity of paraquat and diquat. Drug Chem Toxicol. 1979;2(4):397–408. doi: 10.3109/01480547909016033. [DOI] [PubMed] [Google Scholar]
  9. Kistler G. S., Caldwell P. R., Weibel E. R. Development of fine structural damage to alveolar and capillary lining cells in oxygen-poisoned rat lungs. J Cell Biol. 1967 Mar;32(3):605–628. doi: 10.1083/jcb.32.3.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. McDowell E. M., Trump B. F. Histologic fixatives suitable for diagnostic light and electron microscopy. Arch Pathol Lab Med. 1976 Aug;100(8):405–414. [PubMed] [Google Scholar]
  11. Rose M. S., Smith L. L., Wyatt I. Evidence for energy-dependent accumulation of paraquat into rat lung. Nature. 1974 Nov 22;252(5481):314–315. doi: 10.1038/252314b0. [DOI] [PubMed] [Google Scholar]
  12. Schaffner F., Felig P., Trachtenberg E. Structure of rat lung after protracted oxygen breathing. Arch Pathol. 1967 Jan;83(1):99–107. [PubMed] [Google Scholar]
  13. Sharp C. W., Ottolenghi A., Posner H. S. Correlation of paraquat toxicity with tissue concentrations and weight loss of the rat. Toxicol Appl Pharmacol. 1972 Jun;22(2):241–251. doi: 10.1016/0041-008x(72)90174-3. [DOI] [PubMed] [Google Scholar]
  14. Smith L. L., Lock E. A., Rose M. S. The relationship between 5-hydroxytryptamine and paraquat accumulation into rat lung. Biochem Pharmacol. 1976 Nov 15;25(22):2485–2487. doi: 10.1016/0006-2952(76)90453-6. [DOI] [PubMed] [Google Scholar]
  15. Smith P., Heath D. The ultrastructure and time sequence of the early stages of paraquat lung in rats. J Pathol. 1974 Dec;114(4):177–184. doi: 10.1002/path.1711140402. [DOI] [PubMed] [Google Scholar]
  16. Sykes B. I., Purchase I. F., Smith L. L. Pulmonary ultrastructure after oral and intravenous dosage of paraquat to rats. J Pathol. 1977 Apr;121(4):233–241. doi: 10.1002/path.1711210407. [DOI] [PubMed] [Google Scholar]
  17. Vijeyaratnam G. S., Corrin B. Experimental paraquat poisoning: a histological and electron-optical study of the changes in the lung. J Pathol. 1971 Feb;103(2):123–129. doi: 10.1002/path.1711030207. [DOI] [PubMed] [Google Scholar]
  18. Weibel E. R. Oxygen effect on lung cells. Arch Intern Med. 1971 Jul;128(1):54–56. [PubMed] [Google Scholar]
  19. Witschi H., Kacew S., Hirai K. I., Côté M. G. In vivo oxidation of reduced nicotinamide-adenine dinucleotide phosphate by paraquat and diquat in rat lung. Chem Biol Interact. 1977 Nov;19(2):143–160. doi: 10.1016/0009-2797(77)90027-8. [DOI] [PubMed] [Google Scholar]
  20. Wyatt I., Doss A. W., Zavala D. C., Smith L. L. Intrabronchial instillation of paraquat in rats: lung morphology and retention study. Br J Ind Med. 1981 Feb;38(1):42–48. doi: 10.1136/oem.38.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]

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