Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1995 Apr;50(4):387–391. doi: 10.1136/thx.50.4.387

Attenuation of ischaemia reperfusion injury by human thioredoxin.

T Fukuse 1, T Hirata 1, H Yokomise 1, S Hasegawa 1, K Inui 1, A Mitsui 1, T Hirakawa 1, S Hitomi 1, J Yodoi 1, H Wada 1
PMCID: PMC474289  PMID: 7785012

Abstract

BACKGROUND--Active oxygen species are thought to play a part in ischaemia reperfusion injury. The ability of a novel agent, human thioredoxin (hTRX), to attenuate lung damage has been examined in a rat model of ischaemia reperfusion injury. METHODS--Twenty eight animals were studied. At thoracotomy the left main bronchus and the left main pulmonary artery were clamped for 75 minutes and the lung was then reperfused for 20 minutes. Phosphate buffered saline was administered intravenously to nine control animals and hTRX (30 micrograms/g body weight) was given intravenously to another group of nine animals. Two experiments were carried out. The first (Exp 1) was a time matched pair experiment (five treated, five controls), and the second (Exp 2) was performed under controlled conditions (four treated, four controls; temperature 25 degrees C, humidity 65%). In another 10 nonischaemic rats and those in Exp 1 biochemical measurements of lipid peroxide, superoxide dismutase, and glutathione peroxide levels were performed. RESULTS--In both experiments rats perfused with hTRX survived longer than controls. In Exp 1 the arterial oxygen tension (PaO2) on air in the hTRX group was higher at 20 minutes than at one minute after reperfusion. In Exp 2 PaO2 at 20 minutes was higher in the hTRX group than in the controls. Lipid peroxide, superoxide dismutase, and glutathione peroxide levels in the control group were higher than in the hTRX group and in the non-ischaemic groups. Histological examination showed less thickening and oedema of the alveolar walls in the hTRX group than in controls. CONCLUSIONS--These results suggest that hTRX is effective as a radical scavenger and can limit the extent of ischaemia reperfusion injury of the lungs of experimental animals.

Full text

PDF
387

Images in this article

389Image
on p.389

Selected References

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

  1. Deeb G. M., Grum C. M., Lynch M. J., Guynn T. P., Gallagher K. P., Ljungman A. G., Bolling S. F., Morganroth M. L. Neutrophils are not necessary for induction of ischemia-reperfusion lung injury. J Appl Physiol (1985) 1990 Jan;68(1):374–381. doi: 10.1152/jappl.1990.68.1.374. [DOI] [PubMed] [Google Scholar]
  2. Detterbeck F. C., Keagy B. A., Paull D. E., Wilcox B. R. Oxygen free radical scavengers decrease reperfusion injury in lung transplantation. Ann Thorac Surg. 1990 Aug;50(2):204–210. doi: 10.1016/0003-4975(90)90735-o. [DOI] [PubMed] [Google Scholar]
  3. Flohé L., Günzler W. A. Assays of glutathione peroxidase. Methods Enzymol. 1984;105:114–121. doi: 10.1016/s0076-6879(84)05015-1. [DOI] [PubMed] [Google Scholar]
  4. Flohé L., Otting F. Superoxide dismutase assays. Methods Enzymol. 1984;105:93–104. doi: 10.1016/s0076-6879(84)05013-8. [DOI] [PubMed] [Google Scholar]
  5. Granger D. N., Rutili G., McCord J. M. Superoxide radicals in feline intestinal ischemia. Gastroenterology. 1981 Jul;81(1):22–29. [PubMed] [Google Scholar]
  6. Holmgren A. Thioredoxin. Annu Rev Biochem. 1985;54:237–271. doi: 10.1146/annurev.bi.54.070185.001321. [DOI] [PubMed] [Google Scholar]
  7. Matsuda M., Masutani H., Nakamura H., Miyajima S., Yamauchi A., Yonehara S., Uchida A., Irimajiri K., Horiuchi A., Yodoi J. Protective activity of adult T cell leukemia-derived factor (ADF) against tumor necrosis factor-dependent cytotoxicity on U937 cells. J Immunol. 1991 Dec 1;147(11):3837–3841. [PubMed] [Google Scholar]
  8. Mitsui A., Hirakawa T., Yodoi J. Reactive oxygen-reducing and protein-refolding activities of adult T cell leukemia-derived factor/human thioredoxin. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1220–1226. doi: 10.1016/s0006-291x(05)81536-0. [DOI] [PubMed] [Google Scholar]
  9. Ohkawa H., Ohishi N., Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979 Jun;95(2):351–358. doi: 10.1016/0003-2697(79)90738-3. [DOI] [PubMed] [Google Scholar]
  10. Ohno N., Yokomise H., Fukuse T., Hirata T., Hitomi S., Wada H. Preparation of in-vivo rat lung model for ischemia-reperfusion injury. Thorac Cardiovasc Surg. 1993 Oct;41(5):304–307. doi: 10.1055/s-2007-1013877. [DOI] [PubMed] [Google Scholar]
  11. Parks D. A., Bulkley G. B., Granger D. N. Role of oxygen free radicals in shock, ischemia, and organ preservation. Surgery. 1983 Sep;94(3):428–432. [PubMed] [Google Scholar]
  12. Siegleman S. S., Sinha S. B., Veith F. J. Pulmonary reimplantation response. Ann Surg. 1973 Jan;177(1):30–36. doi: 10.1097/00000658-197301000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Spector A., Yan G. Z., Huang R. R., McDermott M. J., Gascoyne P. R., Pigiet V. The effect of H2O2 upon thioredoxin-enriched lens epithelial cells. J Biol Chem. 1988 Apr 5;263(10):4984–4990. [PubMed] [Google Scholar]
  14. Stewart J. R., Blackwell W. H., Crute S. L., Loughlin V., Greenfield L. J., Hess M. L. Inhibition of surgically induced ischemia/reperfusion injury by oxygen free radical scavengers. J Thorac Cardiovasc Surg. 1983 Aug;86(2):262–272. [PubMed] [Google Scholar]
  15. Tagaya Y., Maeda Y., Mitsui A., Kondo N., Matsui H., Hamuro J., Brown N., Arai K., Yokota T., Wakasugi H. ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction. EMBO J. 1989 Mar;8(3):757–764. doi: 10.1002/j.1460-2075.1989.tb03436.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tagaya Y., Maeda Y., Mitsui A., Kondo N., Matsui H., Hamuro J., Brown N., Arai K., Yokota T., Wakasugi H. ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction. EMBO J. 1989 Mar;8(3):757–764. doi: 10.1002/j.1460-2075.1989.tb03436.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tagaya Y., Wakasugi H., Masutani H., Nakamura H., Iwata S., Mitsui A., Fujii S., Wakasugi N., Tursz T., Yodoi J. Role of ATL-derived factor (ADF) in the normal and abnormal cellular activation: involvement of dithiol related reduction. Mol Immunol. 1990 Dec;27(12):1279–1289. doi: 10.1016/0161-5890(90)90032-u. [DOI] [PubMed] [Google Scholar]
  18. Teshigawara K., Maeda M., Nishino K., Nikaido T., Uchiyama T., Tsudo M., Wano Y., Yodoi J. Adult T leukemia cells produce a lymphokine that augments interleukin 2 receptor expression. J Mol Cell Immunol. 1985;2(1):17–26. [PubMed] [Google Scholar]
  19. Weiss S. J. Oxygen, ischemia and inflammation. Acta Physiol Scand Suppl. 1986;548:9–37. [PubMed] [Google Scholar]
  20. Yokomise H., Fukuse T., Hirata T., Ohkubo K., Go T., Muro K., Yagi K., Inui K., Hitomi S., Mitsui A. Effect of recombinant human adult T cell leukemia-derived factor on rat lung reperfusion injury. Respiration. 1994;61(2):99–104. doi: 10.1159/000196315. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES