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Fast chemical repair of free radical damage to DNA by the constituents and metabolites of beverages
min, and blood pressure was measured at baseline and 60, 90, 120 and 150 min. Chlorogenic acid (400 mg) resulted in significantly higher plasma concentrations of chlorogenic acid (P<0.001). Relative to control, mean post-treatment systolic blood pressure (-2.41 mm Hg, 95% CI: -0.03, -4.78; P=0.05) and diastolic blood pressure (-1.53 mm Hg, 95% CI: -0.05, -3.01; P=0.04) were significantly lower with chlorogenic acid. Markers of NO status (P>0.10) and the measure of endothelial function (P=0.60) were not significantly influenced. Chlorogenic acid can lower blood pressure acutely; an effect which if sustained would benefit cardiovascular health.
strand breaks. Of the wide range compounds investigated, (substituted xanthines, uric acids, phenolics, flavonoids and terpenoids), those possessing relatively low E(1)R values were found to be the most active on a concentration basis. However, only a fraction of the overall damage induced on DNA irradiated in aqueous solution, can undergo such a fast chemical repair process. These studies support a role for the antioxidant mechanism of fast chemical repair of DNA radicals.
Keywords: chlorogenic acid, vascular function, blood pressure, nitric oxide
doi:10.1016/j.freeradbiomed.2012.08.403
doi:10.1016/j.freeradbiomed.2012.08.402
[0329]
[0279]
Quercetin induced autophagy by starvation simulated condition in rat gastric tumor cell line, RGK-1
Fast chemical repair of free radical damage to DNA by the constituents and metabolites of beverages R.F. Anderson*, M.A. Rathod, D. Patel, A. Das The University of Auckland, New Zealand Human cells are subjected to free radicals arising as byproducts in cellular metabolism, as well as ischemia, inflammatory response and from external sources such as ionizing radiation. Hence, protection from deleterious effects of free-radical induced damage to cellular structures, such as DNA, is of interest in the maintenance of health. Epidemiological studies have linked the reduced risk in the induction of certain cancers and neurological disease with the long-term consumption of the common beverages, coffee and tea. One mechanism by which such health benefits are thought to arise is by some of the constituents of these beverages acting as antioxidants in scavenging free radicals. However, the concentrations reached of such compounds in human plasma are too low to effectively intercept highly reactive radicals, such as the .OH radical, in competition to its reaction with cellular targets. An alternative radical mechanism is that active antioxidants can react with long-lived radicals formed on DNA and proteins, thus effecting the fast chemical repair of such lesions. We have used both pulse radiolysis and the plasmid DNA-damage assay system for, in an attempt to rationalise the antioxidant activity of various constituents of coffee and tea on thermodynamic grounds. The radical one-electron reduction potentials of the compounds, E(1)R, have been compared with the activities of the compounds to reduce .OH radical damage to DNA which results in base damage and also
S192
Keywords: beverages, antioxidants, fast chemical repair, DNA
H.P. Indo*1, S. Sriburee2 ,1, H.C. Yen3, H. Matsui4, T. Ozawa5, H.J. Majima1 1 Kagoshima University, Japan, 2Chiang Mai University, Thailand, 3Chang Gung University, Taiwan, 4Tsukuba University, Japan, 5Yokohama College of Pharmacy, Japan Mitochondrial ROS generation was greater for rat gastric mucosal tumor cells RGK-1 than that of its originated rat normal gastric mucosal cells RGM-1. The intrinsic oxygen consumption rate (OCR: pmol/min), extracellular acidification rate (ECAR: mpH/min) were greater in RGK-1 compared with RGM-1, while ATP production was much less in RGK-1 that that in RGM-1. The both cells were treated 200 μM quercetin for 24h. Apoptosis was not observed by quercetin in both cells, but the treatment for 24h resulted in MAP-LC3-II induction in both cells, and more induction was observed in RGK-1 cells, suggesting that the higher rate of autophagy was observed in RGK-1 cells. The treatment resulted severe OCR suppression in RGK-1, while more modest suppression in RGM-1. The ECAR was reduced in RGK1, while the more modest reduction was observed in RGM-1. The gene expressions of mTOR, BECN1 and bcl2 were significantly decreased, but PTEN which is autophagy suppressed gene was not changed in both cells by RT-PCR examinations. These results suggested that quercetin caused autophagy by starvation simulated condition and PI3K-mTOR pathway in RGK-1. Keywords: autophagy, qurcetin, mitochondria, oxygen consumption doi:10.1016/j.freeradbiomed.2012.08.404
strand breaks. Of the wide range compounds investigated, (substituted xanthines, uric acids, phenolics, flavonoids and terpenoids), those possessing relatively low E(1)R values were found to be the most active on a concentration basis. However, only a fraction of the overall damage induced on DNA irradiated in aqueous solution, can undergo such a fast chemical repair process. These studies support a role for the antioxidant mechanism of fast chemical repair of DNA radicals.
Keywords: chlorogenic acid, vascular function, blood pressure, nitric oxide
doi:10.1016/j.freeradbiomed.2012.08.403
doi:10.1016/j.freeradbiomed.2012.08.402
[0329]
[0279]
Quercetin induced autophagy by starvation simulated condition in rat gastric tumor cell line, RGK-1
Fast chemical repair of free radical damage to DNA by the constituents and metabolites of beverages R.F. Anderson*, M.A. Rathod, D. Patel, A. Das The University of Auckland, New Zealand Human cells are subjected to free radicals arising as byproducts in cellular metabolism, as well as ischemia, inflammatory response and from external sources such as ionizing radiation. Hence, protection from deleterious effects of free-radical induced damage to cellular structures, such as DNA, is of interest in the maintenance of health. Epidemiological studies have linked the reduced risk in the induction of certain cancers and neurological disease with the long-term consumption of the common beverages, coffee and tea. One mechanism by which such health benefits are thought to arise is by some of the constituents of these beverages acting as antioxidants in scavenging free radicals. However, the concentrations reached of such compounds in human plasma are too low to effectively intercept highly reactive radicals, such as the .OH radical, in competition to its reaction with cellular targets. An alternative radical mechanism is that active antioxidants can react with long-lived radicals formed on DNA and proteins, thus effecting the fast chemical repair of such lesions. We have used both pulse radiolysis and the plasmid DNA-damage assay system for, in an attempt to rationalise the antioxidant activity of various constituents of coffee and tea on thermodynamic grounds. The radical one-electron reduction potentials of the compounds, E(1)R, have been compared with the activities of the compounds to reduce .OH radical damage to DNA which results in base damage and also
S192
Keywords: beverages, antioxidants, fast chemical repair, DNA
H.P. Indo*1, S. Sriburee2 ,1, H.C. Yen3, H. Matsui4, T. Ozawa5, H.J. Majima1 1 Kagoshima University, Japan, 2Chiang Mai University, Thailand, 3Chang Gung University, Taiwan, 4Tsukuba University, Japan, 5Yokohama College of Pharmacy, Japan Mitochondrial ROS generation was greater for rat gastric mucosal tumor cells RGK-1 than that of its originated rat normal gastric mucosal cells RGM-1. The intrinsic oxygen consumption rate (OCR: pmol/min), extracellular acidification rate (ECAR: mpH/min) were greater in RGK-1 compared with RGM-1, while ATP production was much less in RGK-1 that that in RGM-1. The both cells were treated 200 μM quercetin for 24h. Apoptosis was not observed by quercetin in both cells, but the treatment for 24h resulted in MAP-LC3-II induction in both cells, and more induction was observed in RGK-1 cells, suggesting that the higher rate of autophagy was observed in RGK-1 cells. The treatment resulted severe OCR suppression in RGK-1, while more modest suppression in RGM-1. The ECAR was reduced in RGK1, while the more modest reduction was observed in RGM-1. The gene expressions of mTOR, BECN1 and bcl2 were significantly decreased, but PTEN which is autophagy suppressed gene was not changed in both cells by RT-PCR examinations. These results suggested that quercetin caused autophagy by starvation simulated condition and PI3K-mTOR pathway in RGK-1. Keywords: autophagy, qurcetin, mitochondria, oxygen consumption doi:10.1016/j.freeradbiomed.2012.08.404