Oxidative damage inhibition

Fig. 9 Long-range oxidative damage in DNA is regulated by the structure of the DNA n-stack. Photoexcited [Rh(phi)2(bpy )]3+ intercalated within B-DNA oxidizes guanine doublets positioned 17 A and 40 A away with approximately equal efficiency. When a bulge is introduced in the DNA oxidation at the distal guanine doublet is inhibited. As shown by the NMR structure, bulges introduce local distortions in the DNA r-stack, although the kinking of the helical actually positions the distal guanine closer to the Rh(III) photooxidant...

The effects of antioxidants on protein oxidation were also studied in animal experiments. Barja et al. [73] demonstrated that feeding guinea pigs with vitamin C decreased endogenous protein oxidative damage in the liver. Administration of the mixture of antioxidants containing Trolox C, ascorbic palmitate, acetylcysteine, (3-carotene, ubiquinones 9 and 10, and (+)-catechin in addition to vitamin E and selenium to rats inhibited heme protein oxidation of kidney homogenates more efficiently than vitamin E + selenium [74]. 

The mechanism of benzene-induced toxicity appears to involve the concerted action of several benzene metabolites. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and opened-ring products that are transported to the bone marrow, where secondary metabolism occurs. Metabolites may induce toxicity both by covalent binding to cellular macromolecules and by inducing oxidative damage. Metabolites may also inhibit stromal cells, which are necessary to support growth of differentiating and maturing marrow cells. ... 

As noted above, carnosine has been shown to inhibit protein damage mediated by peroxynitrite and hydroxyl radicals in astroglial cells (Nicoletti et ah, 2007). There is some evidence that carnosine can suppress some of the oxidative damage associated with PD using a model system, and possibly inhibit fibrillization of a-synuclein (Herrera et ah, 2008). 

A similar pattern of reactivity has been observed by Burrows and coworkers for the reaction between A -acetyllysine methyl ester (Lys) and dG. This reaction was studied in order to gain an understanding of structural aspects of DNA-protein cross-links (DPCs). These cross-links are regarded as a common lesion of oxidative damage to cells, but remain, from a chemical point, a poorly understood DNA lesion. As pointed out by Burrows, oxidation of protein-DNA complexes should occur preferentially at the primary amines since these sites have a lower oxidation potential (1.1 V vs. NHE, pH 10) than G. While protonation of the primary amine inhibits the oxidative process, transient deprotonation of a lysine residue would give rise to a lysine aminyl radical (or aminium radical cation). Using... 

Buko, V. et al.. Inhibition of oxidative damage of red blood cells and liver tissue by genistein-8-C-glucoside, Adv. Exp. Med. Biol, 500, 271, 2001. 

The importance of cell death mediated by oxidative damage has led to the popularity of antioxidants as potential therapeutics. A variety of naturally occurring (vitamin C, vitamin E) and synthetic (lazaroids) antioxidants have been smdied as possible remedies for a wide variety of ailments. Large doses of vitamin E have been studied as a putative therapy in Alzheimer s disease, functioning through the inhibition of amyloid-induced oxidative destruction of neuronal membranes within the brain. 

---