Hydroxyl radical scavenging

Herz, H., Blake, D.R and Grootveld, M. (1994). Multicomponent investigations of the hydrogen peroxide- and hydroxyl radical-scavenging antioxidant capacities of biofluids the roles of endogenous pyruvate and lactate. Free Rad. Res. Commun. (in press). 

Moorhouse, C.P., Halliwell, B., Grootveld, M. and Gutteridge, J.M.C. (1985). Cobalt(ll) ion as a catalyst of hydroxyl radical and possible crypto-hydroxy radical formation under physiological conditions. Differential effects of hydroxyl radical scavengers. Biochem. Biophys. Acta 843, 261-268. 

Lovstad, R.A. (1984). Catecholamine stimulation of copper-dependent haemolysis protective action of superoxide dismutase, catalase, hydroxyl radical scavengers and scrum proteins (ceruloplasmin, albumin and apotransferrin). Acta Pharmacol. Toxicol. 54, 340-345. 

Idebenone, an inhibitor of lipid peroxidation, was shown to prolong survival time and delay the onset of ischaemic seizures in a bilateral carotid occlusion model in rats. It is marketed in Japan as a therapy to improve cerebral metabolism and performance after a stroke (Suno and Nagaoka, 1984). Cerebral protective effects after an ischaemic insult in dogs and rabbits have been seen with the hydroxyl radical scavenger, mannitol (Meyer et al., 1987). 

The antiulcer agent rebamipide ((2-(4-chlorobenzoy-lamino)-3-[2(lH)-quinolinon-4-yl]propionic acid) dose-dependently decreased hydroxyl radical signal generated by the Fenton reaction in an e.s.r. study. Rebamipide is active as a hydroxyl radical scavenger and inhibitor of superoxide production by neutrophils (Yoshikawa etal., 1993). 

Ching, T., Haenen, G. and Bast, A. (1993). Cimetidine and other H2 receptor antagonists as powerful hydroxyl radical scavengers. Chem. Biol. Interact. 86, 119-127. 

Tomiyama T, Shoji A, Kataoka K, Suwa Y, Asano S, Kaneko H, Endo N. Inhibition of amyloid beta protein aggregation neurotoxicity by rifampicin. Its possible function as a hydroxyl radical scavenger. J Biol Chem 1996 271 6839-6844. 

The rate law of Eq. (15) holds at all pHs, despite the fact that is strongly pH dependent (see below). Free radical oxidation chemistry (60) appears not to be involved in these Fem-TAML catalyzed oxidations to any detectable degree. The efficient hydroxyl radical scavenger, mannitol (61,62), when added over the concentration range (0.5-2.0) x 10 3 M has no effect on the rate. This peroxide oxidation catalyzed by 1 does not proceed extensively via the hydroxyl free radical serving as the reactive intermediate. 

Subsequent studies confirmed that there is no reliable evidence of the MPO-catalyzed hydroxyl generation by neutrophils [235,236]. Kettle and Winterbourn [237] demonstrated that the hydroxylation of salicylate by stimulated neutrophils or the purified MPO, which yielded 2,5-dihydroxybenzoate, was unaffected by hydroxyl radical scavengers mannitol or DMSO. These authors suggested that an active peroxidative agent in this system was the reduced Compound III, formed by the following reactions ... 

The mechanism of iron-initiated superoxide-dependent lipid peroxidation has been extensively studied by Aust and his coworkers [15-18]. It was found that superoxide produced by xanthine oxidase initiated lipid peroxidation, but this reaction was not inhibited by hydroxyl radical scavengers and, therefore the formation of hydroxyl radicals was unimportant. Lipid peroxidation depended on the Fe3+/Fe2+ ratio, with 50 50 as the optimal value [19]. Superoxide supposedly stimulated peroxidation both by reducing ferric ions and oxidizing ferrous ions. As superoxide is able to release iron from ferritin, superoxide-promoted lipid peroxidation can probably proceed under in vivo conditions [16,20]. 

In 1977, Kellogg and Fridovich [28] showed that superoxide produced by the XO-acetaldehyde system initiated the oxidation of liposomes and hemolysis of erythrocytes. Lipid peroxidation was inhibited by SOD and catalase but not the hydroxyl radical scavenger mannitol. Gutteridge et al. [29] showed that the superoxide-generating system (aldehyde-XO) oxidized lipid micelles and decomposed deoxyribose. Superoxide and iron ions are apparently involved in the NADPH-dependent lipid peroxidation in human placental mitochondria [30], Ohyashiki and Nunomura [31] have found that the ferric ion-dependent lipid peroxidation of phospholipid liposomes was enhanced under acidic conditions (from pH 7.4 to 5.5). This reaction was inhibited by SOD, catalase, and hydroxyl radical scavengers. Ohyashiki and Nunomura suggested that superoxide, hydrogen peroxide, and hydroxyl radicals participate in the initiation of liposome oxidation. It has also been shown [32] that SOD inhibited the chain oxidation of methyl linoleate (but not methyl oleate) in phosphate buffer. 

Spin trapping has been widely used for superoxide detection in various in vitro systems [16] this method was applied for the study of microsomal reduction of nitro compounds [17], microsomal lipid peroxidation [18], xanthine-xanthine oxidase system [19], etc. As DMPO-OOH adduct quickly decomposes yielding DMPO-OH, the latter is frequently used for the measurement of superoxide formation. (Discrimination between spin trapping of superoxide and hydroxyl radicals by DMPO can be performed by the application of hydroxyl radical scavengers, see below.) For example, Mansbach et al. [20] showed that the incubation of cultured enterocytes with menadione or nitrazepam in the presence of DMPO resulted in the formation of DMPO OH signal, which supposedly originated from the reduction of DMPO OOH adduct by glutathione peroxidase. 

Tomiyama, T., Shoji, A., Kataoka, K., Suwa, Y., Asano, S., Kaneko, H., and Endo, N., Inhibition of amyloid beta protein aggregation and neurotoxicity by rifampicin its possible function as a hydroxyl radical scavenger, ]. Biol. Chem., 271, 6839,1996. 

Tamba, M. and Torreggiani, A. (1999). Hydroxyl radical scavenging by carnosine and Cu (ll)-carnosine complexes A pulse-radiolysis and spectroscopic study. Int. ]. Radiat. Biol. 75,1177-1188. 

Figure 7 Comparison of experimental and predicted values of G(p2) from hydroxyl radical scavenging as a function of the scavenger power fcu[S2]. S2 = HCOJ ( ) Fe(CN)g (A). The full and broken lines are the best fits of Eqs. (16) and (17) without any restriction on the parameters (see text). (From Ref 54.)...

At pH >11, where reaction (30) becomes increasingly important, G( OH) can increase by up to 0.6 molecule (100 eV) (i.e., g(H ), whereas at pH < 3, G( OH) becomes smaller because reaction (3) competes with reaction (27). One should not forget that the product of reaction (27) is 0 rather than OH [88,89]. Thus, if a solute that reacts with O in competition with its protonation in reaction (28) is present, then the reaction products may not be the same in N20-saturated solutions containing hydroxyl radical scavengers in high and low concentrations because O can react differently from OH (see Section 4.3). 

This reduces the rotational broadening and makes the vibrational subspectra apparent as a series of multiple peaks. If hydroxyl radical scavengers such as buffer components, the glass or plastic wall of test tubes, or trace metal contaminants are present, exposure to light will result in the formation of nitric oxide from... 

---