Nitric oxide antioxidant reactions

Nitric oxide may also be an antioxidant by virtue of the feet that it can directly inhibit NADPH oxidase and thus prevent superoxide production (Clancy etaJ., 1992). This inhibition was reported to be independent of the reaction between nitric oxide and superoxide, which might be expected to be pro-oxidant (see Section 2.2.3). 

Thus the competition between stimulatory and inhibitory effects of NO depends on the competition between two mechanisms the direct interaction of NO with free radicals formed in lipid peroxidation and the conversion of NO into peroxynitrite or other reactive NO metabolites. Based on this suggestion, Freeman and his coworkers [42-44] concluded that the prooxidant and antioxidant properties of nitric oxide depend on the relative concentrations of NO and oxygen. It was supposed that the prooxidant effect of nitric oxide originated from its reaction with dioxygen and superoxide ... 

As mentioned earlier, ascorbate and ubihydroquinone regenerate a-tocopherol contained in a LDL particle and by this may enhance its antioxidant activity. Stocker and his coworkers [123] suggest that this role of ubihydroquinone is especially important. However, it is questionable because ubihydroquinone content in LDL is very small and only 50% to 60% of LDL particles contain a molecule of ubihydroquinone. Moreover, there is another apparently much more effective co-antioxidant of a-tocopherol in LDL particles, namely, nitric oxide [125], It has been already mentioned that nitric oxide exhibits both antioxidant and prooxidant effects depending on the 02 /NO ratio [42]. It is important that NO concentrates up to 25-fold in lipid membranes and LDL compartments due to the high lipid partition coefficient, charge neutrality, and small molecular radius [126,127]. Because of this, the value of 02 /N0 ratio should be very small, and the antioxidant effect of NO must exceed the prooxidant effect of peroxynitrite. As the rate constants for the recombination reaction of NO with peroxyl radicals are close to diffusion limit (about 109 1 mol 1 s 1 [125]), NO will inhibit both Reactions (7) and (8) and by that spare a-tocopherol in LDL oxidation. 

It has been already pointed out that nitric oxide exhibits antioxidant effect in LDL oxidation at the NO/ 02 ratio 1. Under these conditions the antioxidant effect of NO prevails on the prooxidant effect of peroxynitrite. Although some earlier studies suggested the possibility of NO-mediated LDL oxidation [152,153], these findings were not confirmed [154]. On the other hand, at lower values of N0/02 ratio the formed peroxynitrite becomes an efficient initiator of LDL modification. Beckman et al. [155] suggested that peroxynitrite rapidly reacts with tyrosine residues to form 3-nitrotyrosine. Later on, Leeuwenburgh et al. [156] found that 3-nitrotyrosine was formed in the reaction of peroxynitrite with LDL. The level of 3-nitrotyrosine sharply differed for healthy subjects and patients with cardiovascular diseases LDL isolated from the plasma of healthy subjects contained a very low level of 3-nitrotyrosine (9 + 7 pmol/mol 1 of tyrosine), while LDL isolated from aortic atherosclerotic intima had a 90-fold higher level (840 + 140 pmol/moD1 of tyrosine). It has been proposed that peroxynitrite formed in the human artery wall is able to promote LDL oxidation in vivo. 

Redox reactions involving nitric oxide have important implications beyond their fundamental chemistry as demonstrated by the controversy in the biomedical literature regarding conditions under which generation of NO leads to the amelioration or the exacerbation of oxidative stress in mammalian systems (95). Oxidative stress is defined as a disturbance in the balance between production of reactive oxygen species (pro-oxidants) and antioxidant defenses (96). Reactive oxygen species include free radicals and peroxides as well as other reactants such as oxidative enzymes with metal ion sites in high oxidation states. The... 

Polyphenols can act as antioxidants by a number of potential pathways. The most important is likely to be by free radical scavenging, in which the polyphenol can break the radical chain reaction. Polyphenols are effective antioxidants in a wide range of chemical oxidation systems, being capable of scavenging peroxyl radicals, alkyl peroxyl radicals, superoxide, hydroxyl radicals, nitric oxide and peroxynitrate in aqueous and organic environments [121]. This activity is due to the ability of donating an H atom from an aromatic hydroxyl group to a free radical, and the major ability of an aromatic structure to support an unpaired electron by delocalization around the 7i-electron system. Phenolic acids... 

Enzyme-based biosensors are very suitable for the antioxidant status evaluation, since they show excellent selectivity for biological substances and can directly determine and/or monitor antioxidant compounds in a complex media such as biological or vegetable samples without needing a prior separation step. During the course of the catalytic reaction on the electroactive substrates, the current produced at an applied potential is related to the concentration of a specific biomarker, for which the biosensor is selective. HRP-based biosensors for antioxidant status evaluation have been applied in the detection of superoxide radical [119], nitric oxide [120], glutathione [119, 121], uric acid [122, 123], and phenolic compounds [124—126],... 

Antioxidants 43 Arachidonic acid cascade 44 Radical reactions with DNA 44 Ribonucleotide reductases 45 Vitamin B12 46 Nitric oxide 47 Cytochrome P-450 48 AcetylCoA dehydrogenase 48... 

Recently, research on the biomedical activity of pu-erh tea has focused on its antibacterial, antioxidative, lipid-lowering, and antiobesity effects. Many in vitro studies have shown that pn-erh tea has antioxidative activity. Lin et al. reported that the water extract of pn-erh tea (100 pg/ml) can protect the plasmid DNA from strand breakage indnced by the Fenton reaction as well as the control, regardless of total catechin content. Dnh et al reported that pn-erh tea water extract with less cat-echins (8.01 mg/ml), compared to green tea water extract with more catechins (79.1 mg/ml), could still chelate metal ions, scavenge DPPH radicals, and decrease nitric oxide production in lipopolysaccharide-activated RAW 264.7 macrophages. 

Tea polyphenols show profound antioxidative effects in various systems they are strong scavengers of superoxide, hydrogen peroxide, hydroxyl radicals, nitric oxide, and peroxynitrite, the products of various chemical reactions and biological systems. 

L. Packer V. Kagan E. Cadenas, In Antioxidant Activity of Coenzyme Q and Ubiquinols Reactions with Tocopheroxyl and Nitric Oxide Radicals Proceedings ot the First Conterence ot the International Coenzyme Q-10 Association, Boston, MA, USA, 1998, Abstract pp 22-24. 

Any determination as to whether this reaction of nitric oxide represents a protective mechanism must await further characterization of the primary and secondary reaction products as well as the mechanisms of formation and decomposition. The scavenging of superoxide by nitric oxide was considered to be an antioxidant mechanism before much was known about the product ONOO". 

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