• Title/Summary/Keyword: 8-hydroxy2'-deoxyguanosine

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Control and Mechanism of Tumor Promotion in UV-Carcinogenesis

  • Ueda, Masato;Budiyanto, Arief;Ashida, Masashi;Bito, Toshinori;Ichihashi, Masamitsu
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.221-224
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    • 2002
  • Carcinogenesis can be theoretically divided to intiation step and promotion step. Intiation associates with genetic alterations including p53 tumor suppressor gene and ras oncogene. Promotion involves in clonal expansion of of an initiated cell by epigenetic mechanism, mainly through signal transduction and gene expression. Ultraviolet light (UV) acts as both initiator and promoter. Initiation is closely related with DNA damage induced by UV, including cyclobutane pyrimidine dimers, (6-4) photoproducts and 8-hydroxy-2'-deoxyguanosine. Cyclobutane pyrimidine dimers and (6-4) photoproducts are directly induced by UV, while 8-hydroxy-2'-deoxyguanosine is induced indirectly by the reactive oxygen species. Because initiation is an irreversal genetic event, while promotion is a reversal and epigenetic event, to know the molecular mechanisms of tumor promotion in UV-carcinogenesis is crucial to develop preventive medicine and suppress UV-carcinogenesis. Because ROS is also involved in signal transduction of the cell, anti-oxidant could be the good candidate of anti-promoting agent. Here, we describe the suppressive effect of UV-carcinogenesis by various anti-oxidant including olive oil. In addition, we discuss about the mechanism of UVB-induced expression of cyclooxygenase-2, which might be a representative molecule involved in promotion of UV-carcinogenesis.

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Oxidative stress status and reproductive performance of sows during gestation and lactation under different thermal environments

  • Zhao, Yan;Kim, Sung Woo
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.5
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    • pp.722-731
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    • 2020
  • Objective: Two experiments were conducted using 28 healthy multiparous sows to evaluate the oxidative stress status and reproductive performance of sows during gestation and lactation under different thermal environments. Methods: Fourteen multiparous sows were used in Exp. 1 under a high thermal environment, and the other 14 multiparous sows were used in Exp. 2 under a moderate thermal environment. In both experiments, reproductive performances of sows were recorded. Plasma samples were collected on d 35, 60, 90, and 109 of gestation, and d 1 and 18 of lactation for malondialdehyde, protein carbonyls, 8-hydroxy-deoxyguanosine, immunoglobulin g (IgG), and IgM analysis. Results: For sows in Exp. 1, plasma malondialdehyde concentration on d 109 of gestation tended to be greater (p<0.05) than it on d 18 of lactation. Plasma concentration of protein carbonyl on d 109 of gestation was the greatest (p<0.05) compared with all the other days. Plasma concentrations of 8-hydroxy-deoxyguanosine on d 109 of gestation was greater (p<0.05) than d 18 of lactation in Exp. 1. For sows in Exp. 2, there was no difference of malondialdehyde and protein carbonyl concentration during gestation and lactation. In both Exp. 1 and 2, litter size and litter weight were found to be negatively correlated with oxidative stress indicators. Conclusion: Sows under a high thermal environment had increased oxidative stress during late gestation indicating that increased oxidative damage to lipid, protein, and DNA could be one of the contributing factors for reduced reproductive performance of sows in this environment. This study indicates the importance of providing a moderate thermal environment to gestating and lactating sows to minimize the increase of oxidative stress during late gestation which can impair reproductive outcomes.

Effects of Different Mandarin Formulations on Antioxidative Capacity and Oxidative DNA Damage in Fifteen-Month Aged Rats (부위가 다른 감귤의 섭취가 노령흰쥐의 항산화능 및 DNA손상에 미치는 영향)

  • Kim, Ji-Hye;Kwon, Sang-Hee;Kim, Ja-Kyung;Kim, Mi-Kyung
    • Journal of Nutrition and Health
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    • v.39 no.7
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    • pp.610-616
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    • 2006
  • This study was performed to investigate the effect of whole mandarin, peel or pulp intake of Citrus unshiu Marc. on antioxidative capacity and oxidative DNA damage in fifteen-month aged rats. Forty-eight male Sprague-Dawley rats $(621.9\;{\pm}\;10.1\;g)$ were blocked into four groups according to their body weights as control group, whole mandarin powder group, mandarin peel powder group and mandarin pulp powder group. Rats were raised with diets containing 5% (w/w) freeze dried mandarin formulations for four weeks. Total polyphenol content and total antioxidant status (TAS) of mandarin formulations were highest in peel powder, followed by whole powder and then pulp powder. The 8-hydroxy2'-deoxyguanosine concentrations of kidney in all mandarin groups were significantly lower than that of control group, and that of mandarin peel group was much lower than whole powder and pulp groups. Plasma TAS levels of all the experimental groups were higher than that of control group, and among mandarin groups, peel group showed higher level than remaining two groups. In conclusion, all the mandarin formulations were effective on antioxidative capacity in fifteen-month aged rats, and the peel was most effective one among three formulations.

Antioxidative effects of Houttuynia cordata root on non-lipid oxidative damage (비 지질 산화손상에 대한 어성초 뿌리의 항산화 효과)

  • Hah, Dae-Sik;Kim, Chung-Hui;Kim, Euikyung;Kang, Chung-boo;Kim, Jong-shu
    • Korean Journal of Veterinary Research
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    • v.47 no.1
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    • pp.25-32
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    • 2007
  • Houttuynia cordata root on non-lipid oxidative damage. The antioxidative efects of methanolic (MeOH) extract of Houttuynia cordata rooton non-lipid, including liposome oxidation, oxidation of deoxyribose, protein oxidation, chelating, scavenging,and 2'-deoxyguanosine (2'dG) oxidation were investigated. Houttuynia cordata root exhibited highantioxidative effect in a liposome model system. The inhibitory effect of MeOH extract on deoxyribosedamage exhibited antioxidative effect and it afforded considerable protection against damage to deoxyribose.In addition, MeOH extract at over 300extracts exhibited metal binding ability for hydrogen peroxide. Furthermore, the oxidation of 2'dG to 8-hydroxy-2-deoxyguanosine was inhibited by MeOH extracts, and scavenging activity for hydroxyl radicalexhibited a remarkable effect. The present results on biological model systems showed that MeOH extractswas effective in the protection of non-lipids against various oxidative model systems.

Oxidative Damage to Bacterial DNA and Evicence for Its Repair

  • Park, Jeen-Woo
    • Archives of Pharmacal Research
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    • v.13 no.3
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    • pp.252-256
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    • 1990
  • Oxidative damage to DNA can be caused by excited oxygen species, which are produced by radiation or are by-products of aerobic metabolism. Endogenous evels of 8-hydroxy-2'deoxyguanosine (8-OH-dG), an adduct that results from the damage of DNA caused by hydroxyl radical,have been detected in E. coli and S. typhimurium. Treatment of bacterial cells with various concentrations of hydrogen peroxide caused a moderate increase in the 8-OH-dG content. The enzymatic release of 8-OH-dG from asocorbate/Cu(II)-treated DNA was effected by an extract of E. coli cells. These results indicate that 8-OH-dG is formed in vivo inbacterial DNA through endogenous oxidative mechanisms and on treatment with an oxygen radical-producing agent and that it is repairable.

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Glycation of Copper, Zinc-Superoxide Dismutase and its Effect on the Thiol-Metal Catalyzed Oxidation Mediated DNA Damage

  • Park, Jeen-Woo;Lee, Soo-Min
    • BMB Reports
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    • v.28 no.3
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    • pp.249-253
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    • 1995
  • The nonenzymatic glycation of copper, zinc-superoxide dismutase (Cu,Zn-SOD) led to inactivation and fragmentation of the enzyme. The glycated Cu,zn-SOD was isolated by boronate affinity chromatography. The formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in calf thymus DNA and the generation of strand breaks in pBhiescript plasmid DNA by a metal-catalyzed oxidation (MCO) system composed of $Fe^{3+}$, $O_2$, and glutathione (GSH) as an electron donor was enhanced more effectively by the glycated CU,Zn-SOD than by the nonglycated enzyme. The capacity of glycated Cu,Zn-SOD to enhance damage to DNA was inhibited by diethylenetriaminepentaacetic acid (DETAPAC), azide, mannitol, and catalase. These results indicated that incubation of glycated CU,Zn-SOD with GSH-MCO may result in a release of $Cu^{2+}$ from the enzyme. The released $Cu^{2+}$ then likely participated in a Fenton-type reaction to produce hydroxyl radicals, which may cause the enhancement of DNA damage.

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Correlation of advanced glycation end products and heme oxygenase-1 in Korean diabetic patients (제2형 당뇨병 환자에서 최종당화산물과 heme oxygenase-1의 상관성)

  • Choi, Ha-Neul;Koo, Da-Hye;Yim, Jung-Eun
    • Journal of Nutrition and Health
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    • v.55 no.3
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    • pp.348-358
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    • 2022
  • Purpose: Hyperglycemia accelerates the formation of advanced glycation end products (AGEs), a group of compounds formed via non-enzymatic glycation/glycoxidation. Type 2 diabetes mellitus (T2DM) is related to oxidative stress, resulting in some overgeneration of AGEs. The accumulation of AGEs in T2DM patients leads to increased inflammation, DNA damage, tissue damage, progression of diabetic microvascular disease, and nephropathy. Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme. Expression of HO-1 in the endothelium and in muscle monocytes/macrophages was upregulated upon exposure to reactive oxygen species or oxidized low-density lipoprotein. Cells activated by oxidative stress are reported to release HO-1 in the serum. In the current study, we discuss the oxidative status according to the level of AGEs and the association of HO-1 with AGEs or urinary DNA damage marker in type 2 diabetic Korean patients. Methods: This study enrolled 36 diabetic patients. Subjects were classified into two groups by serum AGEs level (Low AGEs group: < 0.85 ng/mL serum AGEs; High AGEs group: ≥ 0.85 ng/mL serum AGEs). Body composition was measured using bioelectrical impedance analysis. Blood and urinary parameters were measured using commercial kits. Results: No significant differences were observed in the general characteristics and body composition between the two groups. Serum HO-1 concentration was significantly higher in the High AGEs group than in the Low AGEs group. After adjustment of age and gender, a correlation was performed to assess the association between serum HO-1 and serum AGEs or urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Our results indicate that serum HO-1 is positively correlated with serum AGEs and urinary 8-OHdG. Conclusion: Taken together, our results indicate that in diabetes patients, a high level of HO-1 is associated with a high concentration of AGEs and 8-OHdG, probably reflecting a protective response against oxidative stress.

Protection of Peroxynitrite-Induced DNA Damage by Dietary Antioxidants

  • Moon Hye-Kyung;Yang Eun-Sun;Park Jeen-Woo
    • Archives of Pharmacal Research
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    • v.29 no.3
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    • pp.213-217
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    • 2006
  • The present study was undertaken to test the hypothesis that dietary antioxidants protect DNA damage induced by peroxynitrite, a potent physiological inorganic toxin. The present study showed that dietary antioxidants such as (-)-epigallocatechin gallate, quercerin, rutin, resveratrol, and ursolic acid inhibit single strand breaks in supercoiled plasmid DNA induced by 3-morpholinosydnomine N-ethylcarbamide (SIN-1), a generator of peroxynitrite through the reaction between nitric oxide and superoxide anion. The formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in calf thymus DNA by SIN-1 was also inhibited by dietary antioxidants. When U937 cells were incubated with 1 mM SIN-1 bolus, a significant increase of 8-OH-dG level was observed. However, oxidative DNA damage was significantly lower in the cells pre-treated with dietary antioxidants when cells were exposed to SIN-1.

Protective Effects of a Herb, Artemisia capillaris, Against Radiation-induced DNA Damage (방사선 유도 DNA 손상에 대한 인진쑥의 방어효과)

  • Jo, Sung-Kee;Oh, Heon;Cheon, Eui-Hyun;Jeong, U-Hee;Cho, Nam-Jeong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.1
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    • pp.22-27
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    • 2004
  • In the present study, the protective effects of Artemisia capillaris (AC) on the DNA damage induced by $^{60}$ Co ${\gamma}$-rays were evaluated using alkaline single-cell gel electrophoresis (SCGE, comet assay) in the mouse peripheral lymphocytes and micronuclei (MN) formation test in the Chinese hamster ovary (CHO) cells. We also investigated the effect of AC on 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in the mouse liver and thymus exposed to ${\gamma}$-ray, The tail moment and the frequency of MN, which were markers of DNA damage in the SCGE and MN formation test, were decreased in the groups treated with AC extract before exposure to 200 cGy of ${\gamma}$-ray. We also observed its activities, lowering 8-OHdG level, an index of oxidative DNA damage, in the groups treated with AC extract before whole body ${\gamma}$-irradiation (800 cGy). It is plausible that scavenging of free radicals by AC may have played an important role in providing the protection against the radiation-induced damage to the DNA. These results indicated that AC protects the DNA damage induced by ${\gamma}$-rays and might be a useful radioprotector, especially since it is a relatively nontoxic product.

The Effects of Oxidative Stress Induced by Aluminum on Cellular Macromolecules in the Hippocampus and Cerebral Cortex of Rats (알루미늄을 투여한 흰쥐의 해마와 대뇌피질에서 Reactive Oxygen Species 생성으로 인한 생체거대분자의 산화적 손상)

  • Moon Chul-Jin;Koh Hyun-Chul;Shin In-Chul;Lee Eun-Hee;Moon Hae-Ran
    • Toxicological Research
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    • v.20 no.3
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    • pp.213-223
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    • 2004
  • This work aimed to study the effectiveness of cellular oxidative parameter (malondial-dehyde, protein carbonyl, and 8-hydroxy-2'deoxyguanosine). The experimental groups were aluminum treated rats and control rats. Aluminum treatd rats were given intraperitoneally aluminum nitrate nonahydrate ($Al^{3+}$, 0.2 mmol/kg) daily for 30 days except Sunday. Control rats were injected 1 ml of saline. After the dose, rats were decapitated and hippocampus and cerebral cortex were removed. The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation), protein carbonyl (index of protein oxidation), 8-hydroxy-2'-deoxy-guanosine (8-OHdG, index of DNA oxidation), reduced glutathione (GSH) levels as well as glutathione reductase (GR) and catalase. AI concentrations in the tissues were also measured. All results were corrected by tissue protein levels. The results were as followed; 1. The concentrations of AI in the cortex and hippocampus were significantly higher in the AI-treated rats than in the control rats. 2. Antioxidative enzyme's activity, catalase and GR, were significantly higher in the AI-treated rats than the control rats. GSH levels were also higher in the AI-treated rats. 3. MDA, protein carbonyl, and 8-OHdG concentration of AI-treated rats were significantly higher than those of control rats. 4. The concentrations of antioxidants, and oxidative stress parameter were correlated with the concentrations of AI in hippocampus and cerebral cortex. Catalase and GR activity were also correlated with the concentration of AI. Based on these results, it can be suggested that intraperitoneally injected AI was accumulated in the brain and induced the increase of antioxidant levels and antioxidative enzyme activity. Also, the oxidative products of cellular macromolecules are significantly related to tissue AI concentration. Therefore MDA, protein carbonyl, and 8-OHdG are useful markers for oxidative stress on cellular macromolecules.