Spin Traps

Spin trapping can be used to determine the efficiency of various antioxidants toward specific types of free radicals, or the presence of these radicals under various experimental conditions

There are numerous applications in chemistry and biochemistry. Spin trapping is a versatile technique for detecting transient radical species. The method is based on the addition of a compound (the spin trap) to the transient radical species. This reaction yields a more persistent paramagnetic species called the spin adduct, which can be detected and identified by Electron Paramagnetic Resonance (EPR) spectroscopy. The standard by which novel spin traps are evaluated is PBN, (N-tert-butyl-alpha-phenyl nitrone) which has been shown to extend the lives of experimental animals.

How and Why Spin Traps are Used

Spin Traps were originally utilized in measuring free radical activity because they react with free radicals both in vitro and in vivo, producing stable complexes that can be measured by a variety of techniques.1 They are frequently used to measure the efficacy of other antioxidants by measuring the amounts of various free radicals before and after treatment. Later it was discovered that these “spin traps” had powerful free radical quenching abilities in living systems and could treat a variety of conditions, including degenerative age-related diseases because they inhibit fundamental pathogenic mechanisms.2

New evidence surfaces almost daily that free radical pathology underlies many disease processes and aging itself. Antioxidants have become one of the cornerstones of any health maintenance and longevity program. “Spin traps” could provide unique protection against free radical damage that complements and enhances the activities of the classical antioxidants such as vitamin C, vitamin E, glutathione, R-Lipoic Acid and a wide variety of phytochemically derived free radical fighters.3

Spin traps are currently being explored as potential therapeutic agents, as they have been shown to block or reverse the damage associated with a variety of disease states in animal models. It has recently been shown that they exert this benefit by altering signal transduction pathways and reducing systemic inflammation, one of the primary culprits associated with the chronic degenerative diseases of aging. They are effective at doses much lower than those necessary to trap free radicals, and may be more effective with concurrent antioxidant treatment.

Recently, researchers found that the underlying mechanism of “spin trap” activity differs from antioxidants. Spin traps suppress gene transcriptional factors associated with a variety of pathophysiological states.4 In particular, spin traps modulate NF kappa-B regulated cytokines and inducible nitric oxide synthase that are implicated in AIDS, arthritis, arteriosclerosis, Alzheimer’s disease and other pro-inflammatory disease conditions.5 Arguably, this mechanism involves actions at a level proximal to oxidatively sensitive signal amplification systems rather than simple neutralization of free radicals.6

References

  1. Nitrone inhibition of age associated oxidative damage. Floyd, R.A. Ann NY Acad Sci 2000; 899:222-37.
  2. Nitrones, their value as therapeutics and probes to understand aging. Floyd R.A., Hensley K, et al. Mech Ageing Dev. 2002 Apr 30;123(8):1021-31. a) Do Spin Traps also act as classical chain-breaking antioxidants? A quantitative kinetic study of PBN in solution and in liposomes. Free Rad Biol Med 2000 Apr 1; 28 (7) 1079-90
  3. Synthesis and antioxidant efficiency of a new amphiphilic spin-trap derived from PBN and Lipoic Acid. Durand G, Polidori A, et al. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2673-6. a) Unique in vivo applications of spin traps, Berliner, L.J. et. al. Free Rad Biol Med 2001 Mar 1; 30 (5) :489-99
  4. Increased oxidative stress brought on by pro-inflammatory cytokines in neuro- Degenerative processes and the protective role of nitrone based free radical traps. Floyd R.A.; Life Sci 1999; 65 (18-19): 1893-9 a) Expression of cytokines and activation of transcription factors in lipopolysaccharide-administered rats and their inhibition by PBN. Sang, H., Arch Biochem Biophys 1999 Mar 15; 363 (2): 341-8
  5. Spin trap salvage from endotoxemia: the role of cytokine down-regulation. Surgery. 1992 Aug;112(2):130-9; discussion 138-9. Pogrebniak HW, Merino MJ, Hahn SM, Mitchell JB, Pass HI.
  6. Carney J, et al. United States Patent, 5,578,617 November 26, 1996
  7. See the following links for more information: http://www.mcw.edu/frrc/links.htm