title: Effects of epigallocatechin gallate, L-ascorbic acid, alpha-tocopherol, and dihydrolipoic acid on the formation of deoxyguanosine adducts derived from lipid peroxidation.
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.
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA.
authors.forename: Raghu G
authors.initials: RG
authors.lastname: Nath
authors.forename: Mona Y
authors.initials: MY
authors.lastname: Wu
authors.forename: Armaghan
authors.initials: A
authors.lastname: Emami
authors.forename: Fung-Lung
authors.initials: FL
authors.lastname: Chung
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000171:Acrolein / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015227:Lipid Peroxidation; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004281:Docosahexaenoic Acids; D008063:Thioctic Acid; D000171:Acrolein; C015144:dihydrolipoic acid; C060195:cyclic 1,N(2)-propanodeoxyguanosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002392:Catechin; C045651:epigallocatechin gallate; D003849:Deoxyguanosine; D024502:alpha-Tocopherol; D001205:Ascorbic Acid