Mechanistic studies on AMD6221: a ruthenium-based nitric oxide scavenger

Biochemical and Biophysical Research Communications
R MosiSimon P Fricker

Abstract

Nitric oxide is a mediator of many disease states. Previous studies have demonstrated that ruthenium(III) polyaminocarboxylates can react with NO to form stable complexes reducing the levels of nitrite in the culture medium of stimulated RAW264 macrophages and reverse the NO-mediated hypotension in animal models of septic shock. It was necessary to confirm that these observations were due to NO scavenging and not inhibition of the NO metabolic pathway. Using RAW264 cells it was confirmed that [Ru(H(3)dtpa)(Cl)] (AMD6221) was neither acting at the level of iNOS induction, nor as an inhibitor of iNOS by measuring iNOS mRNA by RT-PCR and protein by Western blot and enzyme activity. Using HPLC, the nitrosyl adduct of reaction of AMD6221, [Ru(H(2)dtpa)NO], was identified in the medium of stimulated RAW264 cells co-incubated with AMD6221, concomitant with a stoichiometric reduction in nitrite/nitrate levels, thus confirming that the ruthenium(III) polyaminocarboxylates exert their pharmacological effect by scavenging NO.

References

Dec 11, 1992·The Annals of Thoracic Surgery·S W Downing, L H Edmunds
Sep 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·D J StuehrC F Nathan
Oct 1, 1982·Analytical Biochemistry·L C GreenS R Tannenbaum
Oct 27, 1995·Journal of Medicinal Chemistry·J F KerwinP L Feldman
Dec 30, 1993·The New England Journal of Medicine·S Moncada, A Higgs
Mar 1, 1994·The Biochemical Journal·R G Knowles, S Moncada
Jun 24, 1994·Journal of Medicinal Chemistry·M A Marletta
May 1, 1993·Experimental Physiology·A CalverP Vallance
Aug 28, 1998·Naunyn-Schmiedeberg's Archives of Pharmacology·B Mayer, P Andrew
Sep 16, 1998·Current Opinion in Chemical Biology·B R Babu, O W Griffith
Apr 30, 1999·The Journal of Thoracic and Cardiovascular Surgery·I MayersM W Radomski
Mar 16, 2001·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·G M. PieperS P. Fricker
Mar 27, 2003·The Journal of Thoracic and Cardiovascular Surgery·Irvin MayersMarek W Radomski

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Citations

Jul 8, 2015·The Journal of Physical Chemistry. B·Dharitri Das, Paritosh Mondal
May 19, 2004·British Journal of Pharmacology·Roberta ForestiRoberto Motterlini
Aug 13, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Antonia MaraziotiAndreas Papapetropoulos
Oct 12, 2004·European Journal of Anaesthesiology·M WestphalM Booke
Dec 29, 2004·Free Radical Research·Fernanda M da CunhaJoão B Calixto
Jan 9, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·Ali AlshehriMichel Félétou
Jun 30, 2011·Molecular Cancer Therapeutics·Frederick W FlitneySimon P Fricker
Mar 27, 2003·The Journal of Thoracic and Cardiovascular Surgery·Irvin MayersMarek W Radomski
Feb 23, 2008·Free Radical Biology & Medicine·Galen M Pieper, Allan M Roza

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