Effect of pH on superoxide/hydroperoxyl radical trapping by nitrones: an EPR/kinetic study

Allouch, A.; Lauricella, Robert; Tuccio, Béatrice

doi:10.1080/00268970701494024

Cited by 24 publications

(23 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting that DMPO concentrations used in prior studies did not yield any therapeutic efficacy over the range from 5 to 40 mM (Bradamante et al, 1993;Maurelli et al, 1999), whereas the only reported cardioprotective effect in the perfused rat heart was observed . is significantly enhanced at mildly acidic pH as demonstrated in the work of Allouch et al (2007) and Burgett et al (2008), it may exhibit a more robust protection during ischemia. In the current report, DMPO reduced the magnitude of increase in EDP at all doses tested.…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

The Radical Trap 5,5-Dimethyl-1-PyrrolineN-Oxide Exerts Dose-Dependent Protection against Myocardial Ischemia-Reperfusion Injury through Preservation of Mitochondrial Electron Transport

Zuo¹,

Chen²,

Reyes³

et al. 2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Free radicals are important mediators of myocardial ischemiareperfusion injury. Nitrone spin traps have been shown to scavenge free radicals. The cardioprotective effect of the spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), was investigated in an isolated heart model of global ischemia and reperfusion. Rat hearts were perfused and subjected to global ischemia for 30 min followed by reperfusion with four treatment groups of varying DMPO concentration (0.5-10 mM) administered before induction of ischemia. DMPO treatment improved the recovery of left ventricular (LV) function and coronary flow over the 30-min period of reperfusion compared with untreated hearts. Enhanced recovery was observed for all doses studied but was highest with 1 mM treatment with 2.4-fold higher recovery of LV developed pressure and 37% reduction in infarct size. Superoxide was measured by tissue fluorometry using the O 2 . probe hydroethidine. Hearts treated with 1 mM DMPO showed a significant reduction in O 2 . production compared with control hearts both over the first 5 min of ischemia and upon reperfusion after 30 min of global ischemia. Studies of mitochondrial function demonstrated that 1 mM DMPO increased the

show abstract

Section: Discussionmentioning

confidence: 92%

“…to DMPO is slow at neutral pH; however, at mildly acidic pH, the reactivity is much faster (Finkelstein et al, 1980;Allouch et al, 2007). The high reactivity of O 2 .…”

mentioning

confidence: 99%

The Radical Trap 5,5-Dimethyl-1-PyrrolineN-Oxide Exerts Dose-Dependent Protection against Myocardial Ischemia-Reperfusion Injury through Preservation of Mitochondrial Electron Transport

Zuo¹,

Chen²,

Reyes³

et al. 2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…The trapping rate of superoxide with BMPO is only 0.24 M −1 s −1 at pH7.4 [72]. However, trapping yields with many cyclic nitrones increase dramatically in the presence of hydroperoxyl radical at low pH [73], possibly also with superoxide when the spin trap can be protonated [48]. Our EPR and mass spectral results confirm the trapping of the hydroperoxyl radical unequivocally, suggesting that the trapped hydroperoxyl is formed by the protein during the reaction and released into solution.…”

Section: Resultsmentioning

confidence: 99%

Observation of superoxide production during catalysis of Bacillus subtilis oxalate decarboxylase at pH 4

Twahir¹,

Stedwell²,

Lee³

et al. 2015

Free Radical Biology and Medicine

View full text Add to dashboard Cite

This contribution describes the trapping of the hydroperoxyl radical at a pH of 4 during turnover of wild-type oxalate decarboxylase and its T165V mutant using the spin trap BMPO. Radicals were detected and identified by a combination of EPR and mass spectrometry. Superoxide, or its conjugate acid, the hydroperoxyl radical, is expected as an intermediate in the decarboxylation and oxidation reactions of the oxalate monoanion both of which are promoted by oxalate decarboxylase. Another intermediate, the carbon dioxide radical anion was also observed. The quantitative yields of superoxide trapping is similar in the wild type and the mutant while it is significantly different for the trapping of the carbon dioxide radical anion. This suggests that the two radicals are released from different sites of the protein.

show abstract

“…[124]. The mechanism of nitrone antioxidant activity is intriguing, since at neutral pH, the reactivity of O 2 •− to DMPO is slow, with a second-order rate constant of only 2.0 M −1 s −1 ; however, at acidic pH the reactivity is approximately 27 M −1 s −1 or 10 3 M −1 s −1 at pH 6.2 [136] and 5.0 [124], respectively. The high reactivity of O 2 •− to DMPO in acidic pH was proposed to be due to the protonation of O 2 •− to form hydroperoxyl radical (HO 2 • ), since the pK a for O 2 •− and HO 2 • is 4.8 [137] and 4.4 [138], respectively, and that HO 2 • is a stronger oxidizer than O 2 •− ( E o′ = 1.06 and 0.94 V, respectively) [4].…”

Section: Reactivity Of Nitrones To Superoxidementioning

confidence: 99%

Potential Implication of The Chemical Properties and Bioactivity of Nitrone Spin Traps for Therapeutics

2012

View full text Add to dashboard Cite

Nitrone therapeutics has been employed in the treatment of oxidative stress-related diseases such as neurodegeneration, cardiovascular disease and cancer. The nitrone-based compound NXY-059, which is the first drug to reach clinical trials for the treatment of acute ischemic stroke, has provided promise for the development of more robust pharmacological agents. However, the specific mechanism of nitrone bioactivity remains unclear. In this review, we present a variety of nitrone chemistry and biological activity that could be implicated for the nitrone’s pharmacological activity. The chemistries of spin trapping and spin adduct reveal insights on the possible roles of nitrones for altering cellular redox status through radical scavenging or nitric oxide donation, and their biological effects are presented. An interdisciplinary approach towards the development of novel synthetic antioxidants with improved pharmacological properties encompassing theoretical, synthetic, biochemical and in vitro/in vivo studies is covered.

show abstract

Effect of pH on superoxide/hydroperoxyl radical trapping by nitrones: an EPR/kinetic study

Cited by 24 publications

References 28 publications

The Radical Trap 5,5-Dimethyl-1-PyrrolineN-Oxide Exerts Dose-Dependent Protection against Myocardial Ischemia-Reperfusion Injury through Preservation of Mitochondrial Electron Transport

The Radical Trap 5,5-Dimethyl-1-PyrrolineN-Oxide Exerts Dose-Dependent Protection against Myocardial Ischemia-Reperfusion Injury through Preservation of Mitochondrial Electron Transport

Observation of superoxide production during catalysis of Bacillus subtilis oxalate decarboxylase at pH 4

Potential Implication of The Chemical Properties and Bioactivity of Nitrone Spin Traps for Therapeutics

Contact Info

Product

Resources

About