Prolonging organ allograft survival: potential role of nitric oxide scavengers

BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Galen M PieperAllan M Roza

Abstract

A growing number of studies suggest a key role of nitric oxide (NO) derived from the inducible NO synthase (iNOS) isoform as a signalling molecule leading to acute organ transplant rejection. Current theory suggests that NO targets certain tissue proteins for nitrosylation or nitration leading to inhibition of enzyme/protein function and to cell death via apoptosis. Gene expression of iNOS and formation of nitrotyrosine residues have been confirmed in biopsies of rejecting grafts in humans. Experimental attempts to delay graft rejection by treatment with iNOS enzyme inhibitors have yielded conflicting results. An alternative strategy to alter rejection mediated by NO is to scavenge and/or neutralise the actions of excess NO, thereby by-passing the inhibition of iNOS enzyme activity. This review summarises recent laboratory evidence that new experimental NO scavengers/neutralisers have potential value to prolong graft survival. To date, various metal-based NO scavenging/neutralising compounds have been shown to enhance cardiac allograft survival in the absence of immunosuppression. When used in combination with low-dose cyclosporin, these agents produce a synergistic action to enhance graft survival or even to produce "permanent...Continue Reading

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Citations

Jan 30, 2004·Cytokine & Growth Factor Reviews·Djordje Miljkovic, Vladimir Trajkovic
Aug 3, 2013·Journal of Insect Science·Luigi SalisElena Gordún
Jul 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·H Chaim BirnboimJohn R Webb
Jan 13, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Galen M PieperMark B Adams

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