Abstract
The effects of a complex of dinitrosyl iron with glutathione (DNIC-GS) lyophilized on dextran, its hydrolysis products (glutathione, nitrosoglutathione, dextran), as well as nitric oxide released from the drug on the energy metabolism and functional recovery of isolated perfused rat heart subjected to global ischemia and reperfusion have been studied. Infusion of 100 nM DNIC-GS after ischemia substantially enhanced the recovery of coronary flow, cardiac contractile and pump functions during reperfusion, with simultaneous preservation of myocardial high-energy phosphates and cell membrane integrity. It was shown by EPR that these effects were associated with transfer of Fe+(NO+)2 groups from DNIC-GS to thiol-containing proteins of cardiomyocytes and coronary vessels. Combined infusion of 100 nM DNIC-GS and 25 μM 2-(phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide, a nitric oxide scavenger, after ischemia profoundly reduced the metabolic and functional recovery of reperfused hearts. After postischemic administration of an equivalent amount of DNIC-GS hydrolysate (completely decomposed complex), most of the indices did not differ from those in control or were significantly lower. Thus, inclusion of Fe+(NO+)2 groups into myocardial tissue and spontaneous release of nitric oxide trigger the protective mechanisms in the ischemic heart.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- CFI:
-
contractile function intensity
- Cr:
-
creatine
- DNIC:
-
dinitrosyl iron complex
- GSH:
-
glutathione
- GSNO:
-
S-nitrosoglutathione
- KS:
-
Krebs solution
- LDH:
-
lactate dehydrogenase
- PCr:
-
phosphocreatine
- PTIO:
-
2-(phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide
References
R. D. Rakhit and M. S. Marberb, Heart 86, 368 (2001).
R. Shultz, M. Kelm, and G. Heusch, Cardiovasc. Res. 61, 402 (2004).
A. F. Vanin and E. van Faassen, in Radicals for Live: The Various Forms of Nitric Oxide, Ed. by T. van Faassen and A. F. Vanin (Elsevier, Amsterdam, 2007), pp. 19–74.
O. I. Pisarenko, L. I. Serebryakova, O. V. Tskitishvili, et al., Izv. RAN, Ser. Biol., no. 1, 1 (2008).
O. I. Pisarenko, L. I. Serebryakova, O. V. Tskitishvili, et al., Fiziol. Zh. I.M. Sechenova 95(5), 465 (2009).
S. Levitsky, E. D. Mullin, R. E. Sloane, et al., Circulation 43, I124 (1971).
M. P. Kidd, Altern. Med. Rev. 2, 155 (1997).
M. Nakamura, V. H. Thourani, R. S. Ronson, et al., Circulation 102, III332 (2000).
A. Blaustein, S. M. Deneke, R. I. Stolz, et al., Circulation 80, 1449 (1989).
G. R. Upchurh, G. N. Welch, and A. J. Fabian, J. Biol. Chem. 272, 17012 (1997).
J. Sun, M. Morgan, R.-F. Shen, et al., Circ. Res. 101, 1155 (2007).
E. A. Konorev, M. M. Tarpey, J. Joseph, et al., J. Pharmacol. Exp. Ther. 274, 200 (1995).
A. F. Vanin, V. O. Lozinskii, and V. I. Kapel’ko, RF Patent 2291880 (2005).
O. I. Pisarenko, I. M. Studneva, V. S. Shulzhenko, and A. A. Timoshin, Biomed. Khim. 53(3), 313 (2007).
W. Lamprecht and I. Trautschold, in Methods of Enzymatic Analysis, Ed. by H. U. Bergmeyer (Academic Press, N.Y., 1974), pp. 1777–1781.
E. Bernt, H. U. Bergmeyer, and H. Mollering, in Methods of Enzymatic Analysis, Ed. by H. U. Bergmeyer (Academic Press, N.Y., 1974), pp. 1772–1776.
I. Gutman and A. W. L. Wahlenfeld, in Methods of Enzymatic Analysis, Ed. by H. U. Bergmeyer (Academic Press, N.Y., 1974), pp. 1464–1467.
T. Bucher, R. Czok, W. Lamprecht, and E. Latzko, in Methods of Enzymatic Analysis, Ed. by H. U. Bergmeyer (Academic Press, N.Y., 1974), pp. 2253–2259.
A. A. Timoshin, O. I. Pisarenko, V. L. Lakomkin, et al., Experim. Clin. Cardiol. 5, 59 (2000).
K. A. Reimer, M. L. Hill, and R. B. Jennings, J. Mol. Cell Cardiol. 13(2), 229 (1981).
A. A. Timoshin, A. F. Vanin, Ts. R. Orlova, et al., Nitric Oxide Biol. Chem. 16, 286 (2007).
V. L. Lakomkin, A. F. Vanin, A. A. Timoshin, et al., Nitric Oxide Biol. Chem. 16, 413 (2007).
Author information
Authors and Affiliations
Additional information
Original Russian Text © O.I. Pisarenko, V.S. Shulzhenko, I.M. Studneva, Yu.A. Pelogeikina, A.A. Timoshin, A.F. Vanin, 2009, published in Biofizika, 2009, Vol. 54, No. 6, pp. 1081–1087.
Rights and permissions
About this article
Cite this article
Pisarenko, O.I., Shulzhenko, V.S., Studneva, I.M. et al. Effects of dinitrosyl iron complex with glutathione and its components on ischemic rat heart during reperfusion. BIOPHYSICS 54, 709–713 (2009). https://doi.org/10.1134/S0006350909060104
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0006350909060104