Prooxidant transition

Li, S. Schoneich, C. Borchardt, R. Chemical pathways of peptide degradation. VIII. Oxidation of methionine insmall model peptides by prooxidant/transition metalion systems influence of selective scavengers for reactive oxygen intermediates. Pharm. Res. 1995, 12, 348-355. 

Typical prooxidant transition metal compounds (e.g. iron, cobalt or manganese stearates) are used commercially to induce peroxidation in degradable plastics. However, such prooxidants alone have no practical utility in commercial products unless the prooxidants are deactivated during polymer fabrication, since oxidative degradation begins during... 

The processes described in Schemes 1 and 3 are catalysed by transition metal ions notably by Fe, Co and Mn. Both the decompostion (reactions (4) and (5)) and the consequent formation of hydroperoxides (reactions (6) and (7)) is accelerated, leading to the rapid loss of molar mass in a fraction of the time required for the same change in the absence of a prooxidant transition metal ion. 

In contrast to transition metals iron and copper, which are well-known initiators of in vitro and in vivo lipid peroxidation (numerous examples of their prooxidant activities are cited throughout this book), the ability of nontransition metals to catalyze free radical-mediated processes seems to be impossible. Nonetheless, such a possibility is suggested by some authors. For example, it has been suggested that aluminum toxicity in human skin fibroblasts is a consequence of the enhancement of lipid peroxidation [74], In that work MDA formation was inhibited by SOD, catalase, and vitamins E and C. It is possible that in this case aluminum is an indirect prooxidant affecting some stages of free radical formation. 

Many organic and inorganic compounds, fibers, and particles are capable of damaging nucleic acids by generating reactive oxygen species via the reduction of dioxygen. These stimuli include different classes of organic compounds, classic prooxidants (anticancer antibiotics, various quinones, asbestos fibers, and so on), and even antioxidants, which can be oxidized in the presence of transition metal ions. 

Several studies suggest that LA and DHLA form complexes with metals (Mn2+, Cu2+, Zn2+, Cd2+, and Fe2+/Fe3+) [215-218]. However, in detailed study of the interaction of LA and DHLA with iron ions no formation of iron LA complexes was found [217]. As vicinal dithiol, DHLA must undoubtedly form metal complexes. However, the high prooxidant activity of DHLA makes these complexes, especially with transition metals, highly unstable. Indeed, it was found that the Fe2+-DHLA complex is formed only under anerobic conditions and it is rapidly converted into Fe3+ DHLA complex, which in turn decomposed into Fe2+ and LA [217]. Because of this, the Fe3+/DHLA system may initiate the formation of hydroxyl radicals in the presence of hydrogen peroxide through the Fenton reaction. Lodge et al. [218] proposed that the formation of Cu2+ DHLA complex suppressed LDL oxidation. However, these authors also found that this complex is unstable and may be prooxidative due to the intracomplex reduction of Cu2+ ion. 

The administration of Qio or quercetin to rats protected against endotoxin-induced shock in rat brain [252]. It was found that the pretreatment with these antioxidants diminished the shock-induced increase in brain MDA and nitric oxide levels. Interesting data have been obtained by Yamamura et al. [253] who showed that ubiquinone Qi0 is able to play a double role in mitochondria. It was found that on the one hand, Q10 enhanced the release of hydrogen peroxide from antimycin A- or calcium-treated mitochondria, but on the other hand, it inhibited mitochondrial lipid peroxidation. It was proposed that Q10 acts as a prooxidant participating in redox signaling and as an antioxidant suppressing permeability transition and cytochrome c release. 

Quercetin (Scheme 20.1) a major flavonoid in human diet, acts as a prooxidant [42-44] under certain circumstances. Although the mechanism of interaction of quercetin with DNA is not yet fully understood, there is considerable evidence that quercetin-induced DNA damage occurs via reaction with Cu(II). Quercetin can directly reduce transition metals, thus... 

Wronska-Nofer T, Wisniewska-Knypl J, Wyszynska K. 1999. Prooxidative and genotoxic effect of transition metals (cadmium, nickel, chromium, and vanadium) in mice. Trace Elem Electrolytes 15(2) 87-92. 

Antioxidative reaction pathways. The prevention of damage in cellular systems can be considered a two-level process. First, the cell would minimize the production and availability of prooxidant factors and substances. The compartmentalization of prooxidant enzymes in organelles such as mitochondria, and the sequestering of transition metals by specific proteins are examples of this level of defense. The second level of defense involves the scavenging and neutralization of pro-oxidants. These antioxidant pathways in mitochondria are depicted by darker lines in... 

It seems likely that the prooxidant actions of ascorbate are of relatively little importance in vivo. Except in cases of iron overload, there are almost no transition metal ions in free solution. They are all bound to proteins, and because the renal transport system is readily saturated, plasma and tissue concentrations of ascorbate are unlikely to rise to a sufficient extent to lead to radical formation (Halliwell, 1996 Carr and Frei, 1999a). 

Another explanation was the following. The organomontmorillonite used was a natural montmorillonite that contained iron. Chemical analysis of the clay confirmed the presence of a low amount of iron. It was recalled that iron and, in more general terms, metals are likely to induce the photochemical degradation of polymers. Iron at low concentration had a prooxidant effect that was due to the metal ion of iron that can initiate the oxidation of the polymer by the well-known redox reactions with hydroperoxides [93]. It was concluded that the transition metal ions, such as Fe, displayed a strong catalytic effect by redox catalysis of hydroperoxide decomposition, which was probably the most usual mechanism of filler accelerating effect on polymer oxidation. A characteristic of such catalytic effect was that it did not influence the steady-state oxidation rate, but it shortened the induction time. 

It appears from Figs. 9.5 and 9.6 that there is a huge variation in colour stability between meat from different sources. A range of intrinsic factors influence the oxidative balance in raw meat and thereby the colour stability of the meat (Bertelsen et al., 2000). Thus the oxidative stability of muscles is dependent on the composition, concentrations, and reactivity of (i) oxidation substrates (lipids, protein and pigments), (ii) oxidation catalysts (prooxidants such as transition metals and various enzymes) and (iii) antioxidants, e.g., vitamin E and various enzymes. For review see Bertelsen et al. (2000). 

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