Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1989 Oct;98(2):678–684. doi: 10.1111/j.1476-5381.1989.tb12643.x

Effects of iloprost (ZK 36374) on glutathione status during ischaemia and reperfusion of rabbit isolated hearts.

R Ferrari 1, A Cargnoni 1, S Curello 1, G M Boffa 1, C Ceconi 1
PMCID: PMC1854714  PMID: 2479443

Abstract

1. Reperfusion of rabbit isolated hearts after 60 min of ischaemia resulted in poor recovery of mechanical function, release of creatine phosphokinase (CPK) and of reduced (GSH) and oxidized (GSSG) glutathione, reduction of mitochondrial superoxide dismutase (Mn SOD) activity and of tissue GSH/GSSG ratio with a shift of cellular thiol redox state toward oxidation, suggesting the occurrence of oxidative stress. 2. Pretreatment of the isolated heart with the stable prostacyclin analogue (iloprost) at 27 or 270 nM, but not at 2.7 nM, improved the functional recovery of the myocardium, reduced CPK, GSH and GSSG release, maintained Mn SOD activity and attenuated the occurrence of oxidative stress. 3. This effect of iloprost cannot be explained by a decreased demand or an enhanced delivery of oxygen during ischaemia or by a direct effect on glutathione peroxidase and reductase activity.

Full text

PDF
678

Selected References

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

  1. Adams J. D., Jr, Lauterburg B. H., Mitchell J. R. Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress. J Pharmacol Exp Ther. 1983 Dec;227(3):749–754. [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  3. Ceconi C., Curello S., Cargnoni A., Ferrari R., Albertini A., Visioli O. The role of glutathione status in the protection against ischaemic and reperfusion damage: effects of N-acetyl cysteine. J Mol Cell Cardiol. 1988 Jan;20(1):5–13. doi: 10.1016/s0022-2828(88)80174-3. [DOI] [PubMed] [Google Scholar]
  4. Curello S., Ceconi C., Cargnoni A., Cornacchiari A., Ferrari R., Albertini A. Improved procedure for determining glutathione in plasma as an index of myocardial oxidative stress. Clin Chem. 1987 Aug;33(8):1448–1449. [PubMed] [Google Scholar]
  5. Darius H., Osborne J. A., Reibel D. K., Lefer A. M. Protective actions of a stable prostacyclin analog in ischemia induced membrane damage in rat myocardium. J Mol Cell Cardiol. 1987 Mar;19(3):243–250. doi: 10.1016/s0022-2828(87)80591-6. [DOI] [PubMed] [Google Scholar]
  6. Fantone J. C., Kinnes D. A. Prostaglandin E1 and prostaglandin I2 modulation of superoxide production by human neutrophils. Biochem Biophys Res Commun. 1983 Jun 15;113(2):506–512. doi: 10.1016/0006-291x(83)91754-0. [DOI] [PubMed] [Google Scholar]
  7. Farber N. E., Pieper G. M., Thomas J. P., Gross G. J. Beneficial effects of iloprost in the stunned canine myocardium. Circ Res. 1988 Feb;62(2):204–215. doi: 10.1161/01.res.62.2.204. [DOI] [PubMed] [Google Scholar]
  8. Ferrari R., Cargnoni A., Ceconi C., Curello S., Belloli S., Albertini A., Visioli O. Protective effect of a prostacyclin-mimetic on the ischaemic-reperfused rabbit myocardium. J Mol Cell Cardiol. 1988 Dec;20(12):1095–1106. doi: 10.1016/0022-2828(88)90590-1. [DOI] [PubMed] [Google Scholar]
  9. Ferrari R., Ceconi C., Curello S., Cargnoni A., Agnoletti G., Boffa G. M., Visioli O. Intracellular effects of myocardial ischaemia and reperfusion: role of calcium and oxygen. Eur Heart J. 1986 May;7 (Suppl A):3–12. [PubMed] [Google Scholar]
  10. Ferrari R., Ceconi C., Curello S., Guarnieri C., Caldarera C. M., Albertini A., Visioli O. Oxygen-mediated myocardial damage during ischaemia and reperfusion: role of the cellular defences against oxygen toxicity. J Mol Cell Cardiol. 1985 Oct;17(10):937–945. doi: 10.1016/s0022-2828(85)80074-2. [DOI] [PubMed] [Google Scholar]
  11. Griffiths G. L., Sigel S. P., Payne S. M., Neilands J. B. Vibriobactin, a siderophore from Vibrio cholerae. J Biol Chem. 1984 Jan 10;259(1):383–385. [PubMed] [Google Scholar]
  12. Harris E. J., Booth R., Cooper M. B. The effect of superoxide generation on the ability of mitochondria to take up and retain Ca2+. FEBS Lett. 1982 Sep 20;146(2):267–272. doi: 10.1016/0014-5793(82)80932-0. [DOI] [PubMed] [Google Scholar]
  13. Hess M. L., Okabe E., Kontos H. A. Proton and free oxygen radical interaction with the calcium transport system of cardiac sarcoplasmic reticulum. J Mol Cell Cardiol. 1981 Aug;13(8):767–772. doi: 10.1016/0022-2828(81)90258-3. [DOI] [PubMed] [Google Scholar]
  14. Lefer A. M., Ogletree M. L., Smith J. B., Silver M. J., Nicolaou K. C., Barnette W. E., Gasic G. P. Prostacyclin: a potentially valuable agent for preserving myocardial tissue in acute myocardial ischemia. Science. 1978 Apr 7;200(4337):52–54. doi: 10.1126/science.345441. [DOI] [PubMed] [Google Scholar]
  15. Meerson F. Z., Kagan V. E., Kozlov YuP, Belkina L. M., Arkhipenko YuV The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart. Basic Res Cardiol. 1982 Sep-Oct;77(5):465–485. doi: 10.1007/BF01907940. [DOI] [PubMed] [Google Scholar]
  16. OLIVER I. T. A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochem J. 1955 Sep;61(1):116–122. doi: 10.1042/bj0610116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Paglia D. E., Valentine W. N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967 Jul;70(1):158–169. [PubMed] [Google Scholar]
  18. Schrör K., Addicks K., Darius H., Ohlendorf R., Rösen P. PGI2 inhibits ischemia-induced platelet activation and prevents myocardial damage by inhibition of catecholamine release from adrenergic nerve terminals. Evidence for cAMP as common denominator. Thromb Res. 1981 Jan 1;21(1-2):175–180. doi: 10.1016/0049-3848(84)90046-x. [DOI] [PubMed] [Google Scholar]
  19. Schrör K., Darius H., Matzky R., Ohlendorf R. The antiplatelet and cardiovascular actions of a new carbacyclin derivative (ZK 36 374)--equipotent to PGI2 in vitro. Naunyn Schmiedebergs Arch Pharmacol. 1981 Jun;316(3):252–255. doi: 10.1007/BF00505658. [DOI] [PubMed] [Google Scholar]
  20. Schrör K., Ohlendorf R., Darius H. Beneficial effects of a new carbacyclin derivative, ZK 36 374, in acute myocardial ischemia. J Pharmacol Exp Ther. 1981 Oct;219(1):243–249. [PubMed] [Google Scholar]
  21. Sedlak J., Lindsay R. H. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968 Oct 24;25(1):192–205. doi: 10.1016/0003-2697(68)90092-4. [DOI] [PubMed] [Google Scholar]
  22. Simpson P. J., Mickelson J., Fantone J. C., Gallagher K. P., Lucchesi B. R. Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart. Circ Res. 1987 May;60(5):666–673. doi: 10.1161/01.res.60.5.666. [DOI] [PubMed] [Google Scholar]
  23. Tappel A. L. Lipid peroxidation damage to cell components. Fed Proc. 1973 Aug;32(8):1870–1874. [PubMed] [Google Scholar]
  24. Thiemermann C., Steinhagen-Thiessen E., Schrör K. Inhibition of oxygen-centered free radical formation by the stable prostacyclin-mimetic iloprost (ZK 36 374) in acute myocardial ischemia. J Cardiovasc Pharmacol. 1984 Mar-Apr;6(2):365–366. [PubMed] [Google Scholar]
  25. Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969 Mar;27(3):502–522. doi: 10.1016/0003-2697(69)90064-5. [DOI] [PubMed] [Google Scholar]
  26. de Langen C. D., van Gilst W. H., Wesseling H. Sustained protection by iloprost of the porcine heart in the acute and chronic phases of myocardial infarction. J Cardiovasc Pharmacol. 1985 Sep-Oct;7(5):924–928. doi: 10.1097/00005344-198509000-00017. [DOI] [PubMed] [Google Scholar]
  27. van der Giessen W. J., Schoutsen B., Tijssen J. G., Verdouw P. D. Iloprost (ZK 36374) enhances recovery of regional myocardial function during reperfusion after coronary artery occlusion in the pig. Br J Pharmacol. 1986 Jan;87(1):23–27. doi: 10.1111/j.1476-5381.1986.tb10152.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES