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. 2010;62(5):622-9.
doi: 10.1080/01635580903532424.

Effects of epigallocatechin gallate, L-ascorbic acid, alpha-tocopherol, and dihydrolipoic acid on the formation of deoxyguanosine adducts derived from lipid peroxidation

Raghu G Nath  1 , Mona Y Wu, Armaghan Emami, Fung-Lung Chung
Affiliations

Effects of epigallocatechin gallate, L-ascorbic acid, alpha-tocopherol, and dihydrolipoic acid on the formation of deoxyguanosine adducts derived from lipid peroxidation

Raghu G Nath et al. Nutr Cancer. 2010.

Abstract

Oxidation of polyunsaturated fatty acids (PUFAs) releases alpha,beta-unsaturated aldehydes that modify deoxyguanosine (dG) to form cyclic 1,N(2)-propanodeoxyguanosine adducts. One of the major adducts detected in vivo is acrolein (Acr)-derived 1,N(2)-propanodeoxyguanosine (Acr-dG). We used a chemical model system to examine the effects of 4 antioxidants known to inhibit fatty acid oxidation on the formation of Acr-dG and 8-oxodeoxyguaonsine (8-oxodG) from the PUFA docosahexaenoic acid (DHA) under oxidative conditions. We found that epigallocatechin gallate (EGCG) and dihydrolipoic acid (DHLA) inhibit both Acr-dG and 8-oxodG formation. In contrast, ascorbic acid and alpha-tocopherol actually increase Acr-dG at high concentrations and do not show a concentration-dependant inhibition of 8-oxodG. We also studied their effects on blocking Acr-dG formation directly from Acr. EGCG and DHLA can both effectively block Acr-dG formation, but ascorbic acid and alpha-tocopherol show weak or little effect. These results highlight the complexity of antioxidant mechanisms and also reveal that EGCG and DHLA are effective at suppressing lipid peroxidation-induced Acr-dG and 8-oxodG formation as well as blocking the reaction of dG with Acr.

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Figures

Fig. 1
Fig. 1
Structures of α-OH-Acr-dG, γ-OH-Acr-dG and 8-oxodG.
Fig. 2
Fig. 2
Structures of the antioxidant compounds studied.
Fig. 3
Fig. 3
Typical HPLC chromatograms showing the analysis of the reaction mixture of DHA (3 mM) and dG (15 mM) in the presence of FeSO4 (Panel A) using System 1. The peaks at 26.7 and 33.3 min represent 8-oxodG and γ-OH-Acr-dG, respectively. α-OH-Acr-dG was not detected in this reaction. Panel B shows the analysis of the reaction mixture of Acr (0.5 mM) and dG (0.5 mM) using HPLC System 3. The peaks at 45.0 and 48.2 and 49.5 min represent α-OH-Acr-dG and γ-OH-Acr-dG, respectively.
Fig. 4
Fig. 4
Effects of various concentrations of EGCG (A), ascorbic acid (B), α-tocopherol (C) and DHLA (D) on the formation of γ-OH-Acr-dG in the reaction of DHA with dG in the presence of FeSO4. The values are mean ± standard deviation from 3-4 experiments. *significantly different from the control; n.d., not detectable
Fig. 5
Fig. 5
Effects of various concentrations of EGCG (A), ascorbic acid (B), α-tocopherol (C) and DHLA (D) on the formation of 8-oxodG in the reaction of DHA with dG in the presence of FeSO4. The values are mean ± standard deviation from 3-4 experiments. *significantly different from the control
Fig. 6
Fig. 6
Effects of various concentrations of EGCG (A), ascorbic acid (B), α-tocopherol (C) and DHLA (D) on the formation of Acr-dG adducts (total of α-OH-Acr-dG and γ-OH-Acr-dG) in the reaction of Acr with dG. The values are mean ± standard deviation from 3-4 experiments. *significantly different from the control; n.d., not detected
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References

    1. Nair U, Bartsch H, Nair J. Lipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: A review of published adduct types and levels in humans. Free Radic Biol Med. 2007;43:1109–1120. - PubMed
    1. Refsgaard HHF, Tsai L, Stadtman ER. Modifications of proteins by polyunsaturated fatty acid peroxidation products. Proc Natl Acad Sci U S A. 2000;97:611–616. - PMC - PubMed
    1. Nair J, De Flora S, Izzotti A, Bartsch H. Lipid peroxidation-derived etheno-DNA adducts in human atherosclerotic lesions. Mutat Res. 2007;621:95–105. - PubMed
    1. Negre-Salvayre A, Coatrieux C, Ingueneau C, Salvayre R. Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors. Br J Pharmacol. 2008;153:6–20. - PMC - PubMed
    1. Marnett LJ. Oxy radicals, lipid peroxidation and DNA damage. Toxicology. 2002;181-182:219–222. - PubMed

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