Spin Trap, What is it and why do we love it?

Spin Trap, PHENYL BUTYL NITRONE, NITRONE, PBN, the smart antioxidant that traps free radicals and then converts the free radicals into oxygen that the body can reuse it for tissue respiration.

PBN is the most extensively researched and widely used Spin Trap

Spin Trap Super Antioxidant

The most commonly used spin trap and the standard which measures new ones is PBN – alpha phenyl-N-tert butyl nitrone. Hundreds of studies have been conducted over the last ten years that have tested PBN and other “spin traps” in numerous conditions.⁴ Spin traps have been shown to affect cellular oxidation states and oxidatively sensitive enzyme systems.⁵

PBN has been shown to be an excellent neuroprotective and anti-inflammatory agent.⁶
PBN has extended the life span of mice,⁷ improved cognitive performance in rats,⁸ reversed protein oxidation in aged gerbils and returned them to youthful states.⁹
PBN has attenuated hydroxyl radical formation in ischemia-reperfusion injury,¹⁰ blocked nitric oxide synthase, which minimized the exitotoxicity of peroxynitrite radical.¹¹ Paradoxically, PBN acted as a delivery system for transporting beneficial nitric oxide to targeted areas undergoing oxidative stress.¹²

Low toxicity

PBN has been shown to be of extremely low toxicity even at the highest dosages and with long-term use.^13a,13b The effective dosage of PBN in humans for treating age and ischemic related disorders is expected to be between approximately 1 and 10 mg/70 kg body weight. This equates to 70-700mg for a 70 kg man. Toxicity tests have demonstrated that PBN is completely innocuous, with such low toxicity that it was not possible to determine an LD.sub.50.^13c

Spin Traps work differently than antioxidants

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.¹⁴ 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.¹⁵ Arguably, this mechanism involves actions at a level proximal to oxidatively sensitive signal amplification systems rather than simple neutralization of free radicals.¹⁶

PBN has a wide range of practical applications

Because PBN alters several fundamental cellular processes and metabolic pathways, it may be efficacious for a wide range of conditions. Between the years of 1991 and 2000, researchers, John Carney at University of Kentucky Research Foundation and Robert Floyd at Oklahoma Medical Research Foundation, filed a series of U.S. patents for methods of using PBN. They recommended PBN for many diverse conditions that involve oxidative stress and free-radical pathology.^16-23

Aging

Aging has been demonstrated to be associated with the production of abnormally high levels of oxidized proteins. The consequence of this increased level of protein oxidation is an abnormally low level of critical enzymes in the affected cells. Most, if not all, cells in the body will undergo abnormally high levels of protein oxidation and there will be decreases in antioxidant systems and abnormally low levels of mitochondrial function. The protein oxidation is thought to arise from oxygen free radicals, largely generated via a metal catalyzed reaction within the cell. Studies have now been conducted that daily administration of a free radical spin trapping compound, PBN, for fourteen days completely reverses this process. Not only is the level of protein oxidation decreased, but the abnormally low level of enzyme activity is restored to normal.

Dr. Denham Harman, the father of the Free Radical Theory of Aging, and keynote speaker at the 2nd Annual Anti-aging Conference in Monaco, referred to PBN and spin traps as a ‘breakthrough in anti-aging therapy’ with the potential to significantly slow down the aging process.

PBN Cosmetic Applications

The Standard Nitrone Spin Trap for Cosmetic Applications

Profile

PBN (N-tert-butyl-alpha-phenylnitrone) is the established nitrone “spin trap”. The term “spin trap” is derived from the technique used to detect and identify free radicals, electron spin resonance. Reactive free radicals are attracted and bound to the beta carbon atom in the spin trap, forming a spin adduct and effectively “trapping” the free radical, allowing the structure of the trapped radical to be deduced.

Spin traps are exceptional molecules that can trap and detoxify damaging free radicals which age the skin. PBN blocks and detoxifies harmful free radical molecules from damaging cells and reduces overall systemic inflammation – the culprit recently discovered to underlie all the degenerative diseases of aging.

PBN has been shown to be an excellent neuroprotective and anti-inflammatory agent and transforms skin damaging free radicals into productive regenerative activity.

Cosmetic Applications and Benefits of PBN Powder

PBN can provide unique protection against free radical induced skin damage.
PBN can be administered topically to control inflammatory processes; an underlying cause of skin aging.
PBN is useful for enhancing the activities of topically applied antioxidants such vitamin C, vitamin E and Lipoic Acid and is commonly incorporated into preparations which include other antioxidants.
Spin Traps show promise as blocking agents for inflammation caused by UV exposure. Unlike traditional sunscreens, which prevent UV mediated inflammation when used before exposure, spin trap compounds scavenge free radicals and minimize the inflammatory response during and for up to 12 hours after exposure to UV light. By interfering with the inflammatory cascade, these compounds may prevent collagen and elastin degradation, and thus premature aging of the skin.

Specifications

PBN powder for cosmetic application is doubly recrystalised from high purity solvents and is greater than 98% pure (HPLC). PBN is a white crystalline solid; melting point 73°-74° C. PBN powder is poorly soluble in water, but soluble in alcohols. PBN powder is hydrolyzed at low pH into benzaldehyde and N-tert-butyl-hydroxylamine.

Dr. Denham Harman, the father of the “Free Radical Theory of Aging”, and keynote speaker at the 2nd Annual Anti-aging Conference in Monaco, referred to PBN and spin traps as a “breakthrough in anti-aging therapy with the potential to significantly slow down the aging process.”

In his bestselling book, The Wrinkle Cure, Dr. Nicholas Perricone notes that spin traps are capable of “Stopping Free-Radical Damage Before it Begins…” and that such agents ‘create a barrier – a trap – that holds free radicals in place’ so that they can be “stopped before they scar the cells that make up your skin.” He also claims that researchers “found that the traps actually prevented the free radicals from moving from place to place and damaging cells… and that ‘the odds are these free-radical fighters will become a highly effective method of maintaining a youthful, radiant complexion throughout life… Thanks to a spin trap, we will make quantum leaps in the effort to control the effects of aging…”

References

Nitrone inhibition of age associated oxidative damage. Floyd, R.A. Ann NY Acad Sci 2000; 899:222-37
a) Nitrones, their value as therapeutics and probes to understand aging. Floyd RA, Hensley K, et al. Mech Ageing Dev. 2002 Apr30;123(8):1021-31.
b) 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
a) Synthesis and antioxidant efficiency of a new amphiphilic spin-trap derived from PBN and Lipoic Acid. Durand G, Polidori A, Salles JP, Prost M, Durand P, Pucci B. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2673-6.
b) Unique in vivo applications of spin traps , Berliner, L.J. et. al. Free Rad Biol Med 2001 Mar 1; 30 (5) :489-99
Pharmacokinetics and metabolism of the reactive oxygen scavenger alpha-phenyl-N-tert-butylnitrone in the male Sprague-Dawley rat. Trudeau-Lame ME, Kalgutkar AS, LaFontaine M. Drug Metab Dispos. 2003 Feb;31(2):147-52.
Nitrone-based free radical traps as neuroprotective agents in cerebral ischaemia and other pathologies. Hensley, K. Int Rev Neurobiol 1997; 40: 299-317
a) Antioxidants, oxidative stress, and degenerative neurological disorders. Floyd, R.A., Proc Soc Exp Biol Med 1999 Dec; 222 (3) : 236-45
b) Inhibition of NF-kappaB, iNOS mRNA, COX2 mRNA, and COX catalytic activity by PBN. Kotake, Y., Biochim Biophys Acta 1998 Nov 19; 1448 (1): 77-84
A spin trap, PBN extends the life span of mice. Saito, K; Biosci Biotech Biochem 1998 Apr; 62 (4): 792-4
Antioxidant treatment with PBN improves the cognitive performance and survival of aging rats. Sack, C.A.; Neurosci Lett 1996 Mar 1; 205 (3): 181-4
Effect of the spin trapping compound PBN on protein oxidation and life span. Dubey, A., Arch Biochem Biophys 1995 Dec 20: 324 (2): 249-54

10. PBN attenuates hydroxyl radical production during ischemia-reperfusion injury of rat brain: an EPR study. Sen, S., Free Radic Res Commun 1993: 19 (4) 255-65

11. In vivo or in vitro administration of the nitrone spin-trapping compound, n-tert-butyl-alpha-phenylnitrone, (PBN) reduces age-related deficits in striatal muscarinic receptor sensitivity.Joseph JA, Cao G, Cutler RC.Brain Res. 1995 Feb 6;671(1):73-7.

12. a) Neuroprotective effects of nitrone radical scavenger S-PBN on reperfusion nerve injury in rats. Gray C, Nukada H , Jackson DM, McMorran PD, Wu A , Ma F. Brain Res. 2003 Aug 29;982(2):179-85.
b) ESR characterization of a novel spin-trapping agent, 15N-labeled N-tert-butyl-alpha-phenylnitrone, as a nitric oxide donor. Saito K, Yoshioka, H. Biosci Biotechnol Biochem . 2002 Oct;66(10):2189-93.
c) Differences in cerebral reperfusion and oxidative injury after cardiac arrest in pigs. Liu XL, Wiklund L, Nozari A, Rubertsson S, Basu S. Acta Anaesthesiol Scand. 2003 Sep;47(8):958-67.

13. a) In vitro and in vivo assessment of the irritation potential of different spin traps in human skin. Fuchs J, Groth N , Herrling T. Toxicology. 2000 Oct 26;151(1-3):55-63.
b) Cutaneous tolerance to nitroxide free radicals and nitrone spin traps in the guinea pig. Fuchs J, Groth N , Herrling T. Toxicology. 1998 Feb 20;126(1):33-40.
c) Carney, J, et al. US Patent Application 20050272724, December 8, 2005.

14. 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

15. 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.

16. Carney J, et al. United States Patent, 5,578,617 November 26, 1996

17. Carney J, et al. United States Patent, 6,107,315. August 22, 2000

18. Carney J, et al. United States Patent, 5,405,874. April 11, 1995

19. Carney J, et al. United States Patent, 5,025,032. June 18, 1991

20. Carney J, et al. United States Patent, 5,681,965. October 28, 1997

21. Carney J, et al. United States Patent, 6,002,001. June 18, 1999

22. Carney J, et al. United States Patent, 5,622,994. April 22, 1997

23. Carney J, et al. United States Patent, 5,025,032. June 18, 1991

24. PBN protects against 3,4-methylenedioxymethamphetamine-induced depletion of serotonin in rats. Yeh, S.Y., Synapse 31:169-177 1999