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Effects of Epigallocatechin Gallate, L-Ascorbic Acid, α-Tocopherol, and Dihydrolipoic Acid on the Formation of Deoxyguanosine Adducts Derived From Lipid Peroxidation

Author:
Nath, Raghu G., Wu, Mona Y., Emami, Armaghan, Chung, Fung-Lung
Source:
Nutrition and cancer 2010 v.62 no.5 pp. 622-629
ISSN:
0163-5581
Subject:
lipid peroxidation, ascorbic acids, tocopherols, oxidation, acrolein, antineoplastic agents
Abstract:
Oxidation of polyunsaturated fatty acids (PUFAs) releases α,β-unsaturated aldehydes that modify deoxyguanosine (dG) to form cyclic 1,N2-propanodeoxyguanosine adducts. One of the major adducts detected in vivo is acrolein (Acr)-derived 1,N2-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 α-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 α-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.
Agid:
1461515