Effects of epigallocatechin gallate, L-ascorbic acid, α-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.
- SourceAvailable from: Qin Zhu[Show abstract] [Hide abstract]
ABSTRACT: Acrolein (ACR) is an α,β-unsaturated aldehyde that exists extensively in the environment and (thermally processed) foods. It can also be generated through endogenous metabolism. Its high electrophilicity makes this aldehyde notorious for its facile reaction with biological nucleophiles, leading to the modification of proteins/DNA and depletion of glutathione. Recent studies also have revealed its roles in disturbing various cell signing pathways in biological systems. With growing evidences of ACR's implication in human diseases, strategies to eliminate its hazardous impacts are of great importance. One of the intervention strategies is the application of reactive scavengers to directly trap ACR. Some known ACR scavengers include sulfur (thiol)-containing and nitrogen (amino)-containing compounds as well as the newly emerging natural polyphenols. In this review, the interactions between ACR and its scavengers are highlighted. The discussion about ACR scavengers is mainly focused on their chemical reactivity, trapping mechanisms as well as their roles extended to biological relevance. In addition to their direct trapping effect on ACR, these scavengers might possess multiple functions and offer additional benefits against ACR-induced toxicity. A comprehensive understanding of the mechanism involved may help to establish ACR scavenging as a novel therapeutic intervention against human diseases that are associated with ACR and/or oxidative stress.Molecular Nutrition & Food Research 09/2011; 55(9):1375-90. DOI:10.1002/mnfr.201100149 · 4.91 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Epicatechin belongs to flavonoids protecting cells against oxidative/nitrative stress. Oxidative/nitrative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics. The aim of our study was to establish the effects of epicatechin and antipsychotics action (the first generation antipsychotic (FGA)--haloperidol and the second generation antipsychotic (SGA)--amisulpride) on peroxidation of plasma lipids in vitro. Lipid peroxidation in human plasma was measured by the level of thiobarbituric acid reactive species (TBARS). The properties of epicatechin were also compared with the action of a well characterized antioxidative commercial polyphenol-resveratrol (3,4',5-trihydroxystilbene) and quercetin (3,5,7,3',4'-pentahydroxyflavone). Amisulpride, contrary to haloperidol (after 1 and 24 h) does not significantly influence the increase of plasma TBARS level in comparison with control samples (P > 0.05). After incubation (1 and 24 h) of plasma with haloperidol in the presence of epicatechin we observed a significantly decreases the level of TBARS (P < 0.001, P < 0.001, respectively). In our other experiments, we found that epicatechin also decreased the amount of TBARS in human plasma treated with amisulpride. In conclusion, the presented results indicate that epicatechin-the major polyphenolic component of green tea reduced significantly human plasma lipid peroxidation caused by haloperidol. Moreover, epicatechin was found to be a more effective antioxidant, than the solution of pure resveratrol or quercetin.Neurochemical Research 11/2011; 37(3):557-62. DOI:10.1007/s11064-011-0642-8 · 2.55 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet.Cancer Investigation 06/2013; 31(6). DOI:10.3109/07357907.2013.800095 · 2.06 Impact Factor