Peroxynitrite scavenging and

Mechanism of Peroxynitrite Scavenging and Quenching by Porphyrins and Texaphyrins... 

Haenen GRMM, Paquay JBG, Korthouwer REM and Bast A. 1997. Peroxynitrite scavenging by llavonoids. Biochem Biophys Res Commun 236(3) 591-593. 

Tsuda, T., Kato, Y., and Osawa, T., Mechanism for the peroxynitrite scavenging activity by anthocyanins, FEBS Lett., 484, 207, 2000. 

Hyun, S. K. Jimg, H. A. Chimg, H. Y. S.Choi, J., In vitro peroxynitrite scavenging activity of 6-hydroxykynurenic acid and other flavonoids from Gingko biloba yellow leaves, Arch. Pharm. Res., 2006, 29, 1074-1079. 

Direct antioxidant effects of phenolic compounds include scavenging of several ROS. Epicatechin, for example, is suitable for scavenging nitric oxide [44], superoxide [45],peroxynitrite [46], and for preventing UV-A induced oxidative damage in skin cells [47]. 

Tyrosine Nitration. Tyrosine nitration is one of the protein modifications induced by reactive oxygen species. NO is an important factor that induces posttranslational modifications of proteins by cellular reduction and oxidation mechanism cysteinyl-nitrosylation or Tyr nitration. Nuclear factor (NF)-kappaB activity can be rapidly suppressed by sodium nitroprusside, an NO donor. This effect was effectively reversed by peroxynitrite scavenger deferoxamine, suggesting a Tyr nitration-mediated mechanism. Tyr nitration of p65 induced its dissociation from p50, its association with IxEa, and subsequent sequestration of p65 in the cytoplasm by IkBa-mediated export. LCMS revealed specific nitration on Tyr-66 and Tyr-152 residues of p65, which were confirmed by mutation studies. These residues are important for the direct effects of NO on p65, which resulted in more p65 export and inactivation of NF-kB activity. This study identified a novel and efficient means in which NO rapidly inactivated NF-kB activity by inducing Tyr nitration on p65 [12]. 

Crow JP (2000) Peroxynitrite scavenging by metalloporphyrins and thiolates. Free Radic Biol Med 28 1487-1494... 

The overproduction of NO and oxyradicals in experimental allergic encephalon litis leads to the generation of peroxynitrite. Accordingly, increased nitrotyrosine staining has bwn reported in humans with multiple sderosis, as well as in the active experimental allergic encephalomyelitis lesions. Furthermore, a putative peroxynitrite scavenger has been shown to improve the outcome of experimental allergic encephalomyelitis in mice Pharmacolo cal data direcdy... 

Hall, E.D., Kupina, N.C., and Althaus, J.S. 1999. Peroxynitrite scavengers for the acute treatment of traumatic brain injury. Ann N Y Acad Sci 890 462-468 Handforth, A., and Ackermann, R.F. 1995. Mapping of limbic seizure progressions utilizing the electrogenic status epilepticus model and the 14C-2-deoxyglucose method. Brain Res Brain Res Rev 20(1) 1-23... 

Sinapic acid isolated from B. juncea has peroxynitrite scavenging activity in addition to a dose-dependent inhibition of nitration of BSA and LDL in vitro. ... 

Zou Y, Kim AR, Kim JE, Choi IS, Chung HY. 2002. Peroxynitrite scavenging activity of sinapic acid (3,5-dimethoxy-4-hydroxycinnamicacid) isolated from Brassica juncea. Journal of Agricultural and Food Chemistry, 50 5884—5890. 

The scavenging and quenching mechanism described above would apply to the redox cycle of Mn(III)/Mn(IV) porphyrin or Mn(II)/Mn(III) texaphyrin. The environment of the Mn in the texaphyrin stabilizes the +2 state and does not allow the Mn to become oxidized to +4 (32). Under in vitro conditions, the Mn in the porphyrin exists in the +3 state and does cycle to +4 upon reaction with peroxynitrite (27-31). However, in the presence of reductants (and at much lower oxygen tensions), as would exist intraceUularly, the porphyrin Mn would likely exist in the +2 state a redox cycle from +2 to +4 would allow it to con5)letely reduce peroxynitrite and thereby totally quench its oxidative reactivity (31,30). 

Cohort studies with Mn texaphyrin have not yet been completed. However, preliminary HPLC analysis of end-stage Mn texaphyrin-treated mice indicate lower levels of nitrotyrosine in the spinal cord relative to untreated controls (Dr. Darren Magda, unpublished data 2003). Lowered nitrotyrosine levels, udiether assessed quantitatively by HPLC or qualihitively by immunhistochemistry, are totally consistent with peroxynitrite scavenging by Mn porphyrin and Mn texaphyrin. However, indirect mechanisms involving activation of cellular defense and repair mechanisms may also be playing an inportant role. 

J. P. Crow. Manganese and iron porphyrins catalyze peroxynitrite decomposition and simultaneously increase nitration and oxidant yield inplications for their use as peroxynitrite scavengers in vivo. Arch.Biochem.Biophys. 371 (l) 41-52,1999. 

J. P. Crow. Peroxynitrite scavenging by metallopophyrins and fhiolates. Free Radic.Biol.Med. 28 (10) 1487-1494,2000. 

Graham, A., Hogg, N., Kalyanaraman, B., O Leary, V.J., Darley-Usmar, V. and Moncada, S. (1993). Peroxynitrite modification of low density lipoprotein leads to recognition by the macrophage scavenger receptor. FEBS Lett. 330, 181-185. 

Peroxynitrite (ONOO-) is a cytotoxic reactive species that is formed by the reaction of nitric oxide and superoxide. Methods for measuring the scavenging capacity of peroxynitrite usually depend on either the inhibition of tyrosine nitration or the inhibition of dihydrorhodamine 123 (DHR) oxidation to rhodamine 123 (MacDonalds-Wicks and... 

The 3-morpholinosydnonimine system generates superoxide radicals and nitrogen monoxide, forming peroxynitrite, which releases ethane from KMB (a-keto-y-methiolbutyric acid). This method was used by Lavelli and others (1999) to investigate the radical-scavenging activity of fresh and air-dried tomatoes. 

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