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Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Is homocysteine a pro-oxidant?
B Zappacosta1, A Mordente, S Persichilli
1Instituto di Chimica e Chimica Clinica, CNR Centro Chimica dei Recettori Università Cattolica, Rome, Italy. b.zappacosta@uniserv.ccr.rm.cnr.it
Insights
High homocysteine levels are linked to cardiovascular issues. However, this study found homocysteine does not significantly produce hydrogen peroxide (H2O2) and may even protect against oxidative damage, challenging its role in cardiovascular disease.
Area of Science:
- Biochemistry
- Cardiovascular Science
- Oxidative Stress Research
Background:
- Elevated plasma homocysteine is associated with arterial and venous thrombosis and atherosclerosis.
- Oxidative damage from hydrogen peroxide (H2O2) produced during homocysteine oxidation is a proposed mechanism for these vascular conditions.
Purpose of the Study:
- To accurately quantify H2O2 production during homocysteine oxidation.
- To investigate the interaction of homocysteine with potent oxidants to determine its pro-oxidant potential.
Main Methods:
- Utilized a sensitive assay to measure H2O2 production during homocysteine oxidation.
- Evaluated homocysteine's interaction with hypochlorite, peroxynitrite, and ferrylmyoglobin.
Main Results:
- Homocysteine oxidation yielded negligible H2O2 (1/4000 mole/mole ratio).
- Homocysteine demonstrated significant inhibition of luminol and dihydrorhodamine oxidation by hypochlorite and peroxynitrite.
- Homocysteine rapidly reduced ferrylmyoglobin to metmyoglobin.
Conclusions:
- The findings challenge the established view that homocysteine oxidation is a primary driver of cardiovascular damage.
- Homocysteine may possess antioxidant properties rather than pro-oxidant effects in the context of cardiovascular disease.
Abstract:
High plasma homocysteine concentrations have been found to be associated with atherosclerosis and thrombosis of arteries and deep veins. The oxidative damage mediated by hydrogen peroxide production during the metal-catalyzed oxidation of homocysteine is to date considered to be one of the major pathophysiological mechanisms for this association. In this work, a very sensitive and accurate method was employed to measure the effective production of H2O2 during homocysteine oxidation. Furthermore, the interaction of homocysteine with powerful oxidizing species (hypochlorite, peroxynitrite, ferrylmyoglobin) was evaluated in order to ascertain the putative pro-oxidant role of homocysteine. Our findings indicate that homocysteine does not produce H2O2 in a significant amount (1/4000 mole/mole ratio of H2O2 to homocysteine). Moreover, homocysteine strongly inhibits the oxidation of luminol and dihydrorhodamine by hypochlorite or peroxynitrite and rapidly reduces back ferrylmyoglobin, the oxidizing species, to metmyoglobin. All these results should, in our opinion, lead to a rethinking of the commonly held view that homocysteine oxidation is one of the main causative mechanisms of cardiovascular damage.
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