Search

Abstract Nitroxide free radicals can serve as redox-sensitive MRI contrast agents useful to image the redox status of tissue of interest. In this study, the effect of oxygen content in the inspired gas on the kinetics of metabolism of three nitroxides has been evaluated in the muscle and tumor in mice. SCC tumors (approximate size of 1.0 cm3) on the right hind leg of female C3H/Hen MTV- mice were prepared. Three nitroxides, 3-carboxy-2,2,5,5-tetramethylpyrrolidine- N -oxyl (CxP), 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine- N -oxyl (CmP), and 4-hydroxy-tetramethylpiperidine- N -oxyl (TEMPOL), having different lipophilicities were compared using MR redox imaging. T 1 -mapping of the tissues was obtained using a multi-slice multi-echo (MSME) sequence with several TRs. The three nitroxides showed differences in accumulation and metabolism/clearance in muscle and tumor. The cell impermeable nitroxide CxP displayed kinetic patterns of slow enhancement followed by a slow decline typical of clearance rather than metabolism. The cell permeable CmP on the other hand showed a relatively faster uptake and metabolism with a modestly higher rate of metabolism in the tumor than muscle. The TEMPOL on the other hand displayed a rapid uptake and reduction with a trend of significantly rapid decay rate in tumor tissue, while slightly higher maximum signal intensity and slower decay rate was observed in normal muscle. The reduction rate of TEMPOL in the tumor was significantly enhanced when the breathing gas had 100%-oxygen while it was not significantly different in the muscle. EPR oximetry studies monitoring the oxygen dependent linewidth of TEMPOL showed that the pO 2 in the healthy tissue during carbogen breathing significantly increased normal tissue pO 2 compared to air breathing whereas breathing 100%-oxygen made normal tissue slight hypoxic. Since TEMPOL is a radioprotector, our studies show that a combination of 100%-oxygen breathing and TEMPOL has a potential to enhance radioprotective effects to normal tissue. Highlights • 100%-O 2 breathing makes the decay rate of TEMPOL in tumor tissue faster. • 100%-O 2 breathing makes the decay rate of TEMPOL in the normal muscle slower. • 100%-O 2 breathing did not affect to the normal tissue pO 2. • 100%-O 2 makes difference of TEMPOL conc. between normal and tumor tissues larger. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study is to test the performance of multispin nitroxyl contrast agents in improving the sensitivity of MR detection for nitroxyl contrast agents. The relation between T 1 relaxivity and the number of paramagnetic centers in a molecule was investigated. Compound 1 is a single molecule of methoxycarbonyl-PROXYL (MC-PROXYL). Two and three MC-PROXYL molecules were chemically coupled to obtain Compounds 2 and 3, which have two and three nitroxyl spins in the molecule, respectively. A good linear relation, the slope of which increased depending on the number of nitroxyl spins in the molecule, was obtained between T 1-weighted (fast low-angle shot) MR image contrast enhancement at 7 T and the concentration of nitroxyl contrast agents. T 1-weighted MR image contrast enhancement and T 1 relaxivity levels of nitroxyl contrast agents were increased depending on the number of nitroxyl spins in the molecule. Multicoupling nitroxyl molecules can enhance the T 1-weighted contrast effect while maintaining the quantitative behavior of the molecule for up to three spins. [Copyright &y& Elsevier]

Abstract: The free radical-reducing activity and the membrane fluidity of liver microsomes from selenium-deficient (SeD) rats were examined by means of electron paramagnetic resonance (EPR) spin label method using nitroxyl-labeled stearic acids. Our findings show that the membrane fluidity and lipid peroxidation levels in SeD rat liver microsome were relatively unchanged compared with normal rat. In contrast, SeD caused the induction of liver microsomal cytochrome P-450 activity. The nitroxyl spin probes are substrates for reduction-relating cytochrome P-450. Previous in vivo studies suggested that the total liver free radical reduction activity in SeD rat was decreased. In contrast, SeD caused the induction of liver microsomal cytochrome P-450 activity, and the reduction rate of nitroxyl radical existing at shallow depth in membrane was increased. Selenium-deficient rats experienced an increase in hydrogen peroxide (H2O2) due to a pronounced loss of glutathione peroxidase (GSH-Px) activity. This masked the overall reduction rate of the nitroxyl spin probe by reoxidation of the hydroxylamine form. Although the SeD condition caused induction of liver cytochrome P-450 and chronic increased H2O2, this did not result in oxidative liver damage. An increased level of glutathione in SeD liver was also evident, likely due to the absence of GSH-Px activity. Using the EPR spin label method, we have shown that SeD causes complicated redox changes in the liver, notably, alterations in the levels of cytochrome P-450 and GSH-Px systems. [Copyright &y& Elsevier]

The effect of oxygenation challenges to the in vivo pharmacokinetics of nitroxyl contrast agents in squamous cell carcinoma (SCC) tumor tissue and normal muscle was investigated. In addition, difference of T 1 relaxivity ( Δ R 1 ) in the normal muscle and the SCC tumor tissues were compared under several gas-challenging conditions. SCC tumor cells were injected into the right thighs of C3H/Hen MTV - female mice and allowed to grow for 9 days, which resulted in a tumor of approximate size of 0.7 cm 3 . Pharmacokinetic profiles of three nitroxyl contrast agents, 3-carboxy-2,2,5,5-tetramethyl-pyrrolidine- N -oxyl (CxP), 3-carbamoyl-2,2,5,5-tetramethyl-pyrrolidine- N -oxyl (CmP), and 4-hydroxy-tetramethylpiper-idine- N -oxyl (TPL), having different lipophilicities were compared using MR redox imaging. To perform T 1 mapping, spin echo images were obtained using a multi-slice multi-echo (MSME) sequence with 5 TRs (repetition time: 4800, 3200, 1600, 800 and 400 ms). Exposure to 100% oxygen resulted in a rapid decay rate of TPL in tumor tissue, while no effect or slightly slower decay rate was observed in normal muscle. The 100% oxygen breathing also made distribution of nitroxyl probes into tissue lower. As a result, 100% oxygen breathing can make relatively large difference of TPL concentration between normal and tumor tissue. Carbogen and 1.5 atm hyperbaric oxygen (HBO) challenges could increase Δ R 1 in the tissue, while 100% oxygen breathing decreased the Δ R 1 in both the normal and the tumor tissue. The pO 2 in the healthy muscle tissue during 100% oxygen breathing measured by the EPR method also showed lower or similar values compared to the air breathing. Pimonidazole staining confirmed that 100% oxygen breathing increased hypoxia in tumor tissue. A combination of 100% oxygen with TPL has a potential to enhance the radioprotection selectively in normal tissues. [ABSTRACT FROM AUTHOR]

Generation of reactive oxygen species (ROS) is considered as essential trigger of biological effects of ionizing radiations, and may be deeply linked with the radiation quality. Amounts of total oxidation reactions (i.e. oxidative free radical species, ● OH and HO 2●– ), H 2 O 2 generations, Oxygen consumptions, and • OH generations induced by X-ray, 20 keV/μm carbon beam, and 80 keV/μm carbon beam were estimated using EPR based techniques. Total oxidation reactions were estimated as 3, 1.3, and 0.66 μmol/L/Gy, amount of H 2 O 2 generations were 0.2, 0.57, and 0.35 μmol/L/Gy, oxygen consumptions were 0.4, 0.39, and 0.15 μmol/L/Gy for X-ray, 20 keV/μm carbon beam, and 80 keV/μm carbon beam, respectively. The ratio of H 2 O 2 generation per oxygen consumption were increased with LET, and were 0.5, 1.46, 2.33 for X-ray, 20 keV/μm carbon beam, and 80 keV/μm carbon beam, respectively. The ● OH generations expected to be localized on the track/range of the radiation beam/ray, and both sparse (≈ 3.3 mM) and very dense (> 1.7 M) ● OH generations were suggested. Percentage of sparse ● OH generation decreased with LET becoming higher. [ABSTRACT FROM AUTHOR]

Proanthocyanidins are oligomers of catechins that exhibit potent antioxidative activity and inhibit binding of oxidized low-density lipoprotein (OxLDL) to the lectin-like oxidized LDL receptor (LOX-1), which is involved in the onset and development of arteriosclerosis. Previous attempts aimed at developing proanthocyanidin derivatives with more potent antioxidative activity and stronger inhibition for LOX-1 demonstrated the synthesis of a novel proanthocyanidin derivative ( 1 ), in which the geometry of one catechin molecule in procyanidin B3 was constrained to a planar orientation. The radical scavenging activity of 1 was 1.9-fold higher than that of procyanidin B3. Herein, we synthesized another procyanidin B3 analogue ( 2 ), in which the geometries of both catechin molecules in the dimer were constrained to planar orientations. The radical scavenging activity of 2 was 1.5-fold higher than that of 1 , suggesting that 2 may be a more effective candidate than 1 as a therapeutic agent to reduce oxidative stress induced in arteriosclerosis or related cerebrovascular disease. [ABSTRACT FROM AUTHOR]

Abstract: Cyclic nitroxides are a diverse group of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15–20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described, including their ability to degrade superoxide and peroxide, inhibit Fenton reactions, and undergo radical–radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use, including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. Although much remains to be done, many applications have been well studied and some are currently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials. [Copyright &y& Elsevier]

Purpose: Autophagy and cell-cycle checkpoints act in concert to confer cellular radioresistance. We investigated the functional interaction between radiation-induced autophagy and G2 checkpoint activation in highly radioresistant human pancreatic ductal adenocarcinoma (PDAC) cells.Methods and Materials: Four human PDAC cell lines (MIA PaCa-2, KP-4, Panc-1, and SUIT-2) were analyzed. These cells were first irradiated using x-rays, and their cell cycle status, autophagy, and cell cycle checkpoint marker expression and ATP production levels were evaluated. Autophagic flux assays and siRNA knockdown were used to evaluate autophagy activity. Double thymidine block experiments were performed to synchronize the cells. Two inhibitors (MK-1775 and SCH 900776) were used to attenuate G2 checkpoint activation. Cell survival assays and animal experiments were performed to evaluate the radiosensitizing effects of the G2 checkpoint inhibitors.Results: Autophagy and G2/M accumulation were synchronously induced in human PDAC cells with an activated G2 checkpoint at 12 hours after x-ray irradiation of 6 Gy. Radiation-induced autophagy produced the ATP levels required for cell survival. Double thymidine block experiments revealed that no autophagy occurred in cells that were solely in G2 phase. MK-1775 or SCH 900776 exposure attenuated not only G2 checkpoint activation but also postirradiation autophagy, indicating the dependence of radiation-induced autophagy on an activated G2 checkpoint. The inhibitors demonstrated a higher radiosensitizing effect in the PDAC cells than the autophagy inhibitor chloroquine. MK-1775 in combination with x-rays significantly suppressed the tumor growth of MIA PaCa-2 xenografts compared with other treatment groups, including radiation or drug exposure alone, to enhance the radiosensitivity of PDAC cells in vivo.Conclusions: Biological crosstalk exists between the G2 checkpoint activation and radiation-induced autophagy processes that are believed to independently contribute to the radioresistance of human PDAC cells. These findings have important implications for the development of future radiation therapy strategies for PDAC. [ABSTRACT FROM AUTHOR]

Time courses of the redox status in the brains of mice after X-ray or carbon-ion beam irradiation were observed by magnetic resonance redox imaging (MRRI). The relationship between radiation-induced oxidative stress on the cerebral nervous system and the redox status in the brain was discussed. The mice were irradiated by 8-Gy X-ray or carbon-ion beam (C-beam) on their head under anesthesia. C-beam irradiation was performed at HIMAC (Heavy-Ion Medical Accelerator in Chiba, NIRS/QST, Chiba, Japan). MRRI measurements using a blood-brain-barrier-permeable nitroxyl contrast agent, MCP or TEMPOL, were performed using 7-T scanner at several different times, i.e., 5–10 h, 1, 2, 4, and 8 day(s) after irradiation. Decay rates of the nitroxyl-enhanced T 1 -weighted MR signals in the brains were estimated from MRRI data sets, and variation in the decay rates after irradiation was assessed. The variation in decay rates of MCP and TEMPOL after X-ray or C-beam irradiation was similar, but different variation patterns were observed between X-ray and C-beam. The apparent decay rate of both MCP and TEMPOL decreased due to the temporal reduction of blood flow in the brain several hours after X-ray and/or C-beam irradiation. After decreasing, the apparent decay rates of nitroxyl radicals in the brain gradually increased during the following days after X-ray irradiation or rapidly increased 1 day after C-beam irradiation. The sequential increase in nitroxyl decay rates may have been due to the oxidative atmosphere in the tissue due to ROS generation. X-ray and C-beam irradiation resulted in different redox responses, which may have been due to time-varying oxidative stress/injury, in the mouse brain. The C-beam irradiation effects were more acute and larger than those of X-ray irradiation. Image 1 • Amphiphilic nitroxyl radicals could be BBB-permeable functional MR contrast agents. • Redox status in a mouse brain was estimated by magnetic resonance redox imaging. • Temporal reduction of blood flow in the brain hours after irradiation was expected. • Delayed ROS generation days after irradiation were expected in the brain. • X-ray and C-beam irradiation resulted in different redox responses in the brain. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The radical-scavenging reaction of fisetin, a natural antioxidant found in strawberries, is known to proceed via hydrogen transfer to produce a fisetin radical intermediate. Thus, introduction of an electron-donating group into the fisetin molecule is expected to stabilize the radical, leading to enhanced radical-scavenging activity. In this study, fisetin derivatives in which methyl substituents were introduced at the ortho positions relative to the catechol hydroxyl groups were synthesized and their radical scavenging activities were evaluated and compared with that of the parent fisetin molecule. Among the methyl derivatives, 5′-methyl fisetin, in which the inherent planar structure of fisetin was retained, exhibited the strongest radical scavenging activity. Introduction of methyl substituents may be effective for the enhancement of various biological activities of antioxidants, particularly radical-scavenging activity. [ABSTRACT FROM AUTHOR]

Hydroxyl radical ( ● OH) is recognized a key player in biological effects of radiation. In this study, X-ray or heavy-ion beam induced ● OH generation was evaluated using fluorescent probe method. The eccentrically-located ● OH generations and the super-localized ● OH generations, which were previously reported based on EPR spin-trapping method, were again confirmed with a different types of analysis. Several concentrations (0.5-208 mM) of terephthalic acid disodium (TPA-Na) in aqueous solution were irradiated with 32 Gy X-ray or a heavy-ion beam (C400, Si490 or Fe500). The amount of ●• OH adduct of TPA-Na (hydroxyl terephthalate: hTPA) generated was measured by fluorophotometer (Ex.310 nm/Em. 425 nm). The relationship between the molecular density of TPA-Na in the reaction mixture and hTPA generated was analyzed. The amount of hTPA was increased in proportion to the molecular density of TPA-Na and reached plateau. The inflexion point was not changed by type of ray. The inflexion point suggests the relatively a concentration of ● OH generation. In the case of heavy-ion beam, another linear trend that passed through the origin was again observed when TPA-Na density was extremely high. This second linear increasing of hTPA suggested extremely "dense" generation of ● OH. [ABSTRACT FROM AUTHOR]

2,2-Diphenyl-1-picrylhydrazyl radical (DPPH ● ) is a relatively stable radical and frequently used as a reactivity model of reactive oxygen species. However, its insolubility in water precludes the investigation of the redox behavior of DPPH ● in aqueous media, especially in concentrated buffer solutions. We have recently reported that DPPH ● can be successfully solubilized in water by β -cyclodextrin ( β -CD). The as-obtained β -CD-solubilized DPPH ● (DPPH ● / β -CD) was demonstrated to be a powerful tool for evaluating the antioxidative activity of water-soluble antioxidants, such as ascorbic acid, Trolox, and caffeic acid, in concentrated buffer solutions. In this study, the redox behavior of DPPH ● / β -CD was investigated by cyclic voltammetry. A well-defined reversible redox wave was observed for one-electron reduction of DPPH ● / β -CD in phosphate buffer (0.1 M, pH 7.4). On the other hand, one-electron oxidation of DPPH ● / β -CD showed a quasi-reversible redox wave, which suggests that DPPH cations (DPPH + ) generated by the electrochemical one-electron oxidation may undergo a follow-up chemical reaction, such as an addition of a water molecule. [ABSTRACT FROM AUTHOR]

Proanthocyanidin, an oligomer of catechin, is a natural antioxidant and a potent inhibitor of lectin-like oxidized LDL receptor-1, which is involved in the pathogenesis of arteriosclerosis. We synthesized proanthocyanidin analogue 1 , in which the geometry of one catechin molecule in procyanidin B3, a dimer of (+)-catechin, is constrained to be planar. The antioxidant activities of the compounds were evaluated in terms of their capacities to scavenge galvinoxyl radicals, and results demonstrate that while procyanidin was 3.8 times more potent than (+)-catechin, the radical scavenging activity of proanthocyanidin analogue 1 was further increased to 1.9 times that of procyanidin B3. This newly designed proanthocyanidin analogue 1 may be a promising lead compound for the treatment of arteriosclerosis and related cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Abstract: Nitroxides are a class of stable free radicals that have several biomedical applications including radioprotection and noninvasive assessment of tissue redox status. For both of these applications, it is necessary to understand the in vivo biodistribution and reduction of nitroxides. In this study, magnetic resonance imaging was used to compare tissue accumulation (concentration) and reduction of two commonly studied nitroxides: the piperidine nitroxide Tempol and the pyrrolidine nitroxide 3-CP. It was found that 3-CP was reduced 3 to 11 times slower (depending on the tissue) than Tempol in vivo and that maximum tissue concentration varies substantially between tissues (0.6–7.2mM). For a given tissue, the maximum concentration usually did not vary between the two nitroxides. Furthermore, using electron paramagnetic resonance spectroscopy, we showed that the nitroxide reduction rate depends only weakly on cellular pO2 in the oxygen range expected in vivo. These observations, taken with the marked variation in nitroxide reduction rates observed between tissues, suggest that tissue pO2 is not a major determinant of the nitroxide reduction rate in vivo. For the purpose of redox imaging, 3-CP was shown to be an optimal choice based on the achievable concentrations and bioreduction observed in vivo. [ABSTRACT FROM AUTHOR]

Abstract: A procedure for estimating in vivo redox status using EPR and a hydrogen peroxide (H2O2)-dependent spin probe method is described. The mechanism of decreasing spin clearance in the selenium-deficient (SeD) rat is discussed. The in vivo decay constant of the nitroxyl spin probe in the liver region of SeD rats appeared to be slightly lower that of the selenium-adequate control (SeC) group, and was significantly smaller than that of normal rats. Bile H2O2 levels in normal rats were significantly lower than those in SeD rats. The in vivo decay constant of the spin probe in SeD rats depended on the bile H2O2 level. Furthermore, H2O2 was detected in the bile in all SeD rats, whereas bile H2O2 could be detected in only half of the normal rats. It was found that the in vivo decay constant of the spin probe in normal rats also depended on whether bile H2O2 was detected or not. In vivo decay constants were smaller in rats subjected to the surgical operation than in the nonoperated groups. The EPR signal of the nitroxyl radical in the liver homogenate was increased by addition of H2O2, which was administered 30 min before the rat was killed. It appears that H2O2 can oxidize the hydroxylamine formed following reduction of the spin probe in the liver. [Copyright &y& Elsevier]

Abstract: Catechin analogue 1 with methyl substituents ortho to the catechol hydroxyl groups was synthesized to improve the antioxidant ability of (+)-catechin. The synthetic scheme involved a solid acid catalyzed Friedel–Crafts coupling of a cinnamyl alcohol derivative to 3,5-dibenzyloxyphenol followed by hydroxylation and then cyclization through an intermediate orthoester. The antioxidative radical scavenging activity of 1 against galvinoxyl radical, an oxyl radical, was found to be 28-fold more potent than (+)-catechin. [Copyright &y& Elsevier]

Glutathione (GSH) is known to act as a redox regulator. However, the radical-scavenging mechanism of GSH has yet to be fully clarified. Recently, we have succeeded in solubilizing water-insoluble 2,2-diphenyl -1-picrylhydrazyl (DPPH) radical in water using beta-cyclodextrin. In this study, the scavenging mechanism of the water-solubilized DPPH radical by GSH was investigated using the stopped-flow technique. Upon mixing of GSH with the DPPH radical in phosphate buffer (0.05 M, pH 7.4), the absorption band at 527 nm due to the DPPH radical decreased gradually. The pseudo-first order rated constants (kobs), determined from the decay of the absorbance at 527 nm, increased with increasing the GSH concentration and reached a constant value. Furthermore, the higher pH was, the larger the kobs values became. When H2O of the phosphate buffer was replaced with D2O, little change was observed for the kobs values. Thiol compounds with smaller pKa values than GSH, such as L-cysteine, showed higher scavenging activity than GSH under the same experimental conditions. These results suggest that the DPPH radical-scavenging reaction by GSH may proceed via deprotonation of GSH to produce the corresponding thiolate anion, GS-, followed by an electron transfer from GS- to the DPPH radical. [ABSTRACT FROM AUTHOR]

Relatively young (8-week-old) selenium deficient (SeD) mouse model was prepared using SeD diet. Selenium (Se), which is an essential trace element, has important roles in the biological redox regulation system as the catalytic center of glutathione peroxidases (GSH-Px). Mice were fed on torula yeast based SeD diet (F2SeDD, Oriental Yeast Co., Ltd., Tokyo) and ultra-pure water (mili-Q water). Several different timings for starting SeD diet were demonstrated and weekly time course of liver GSH-Px activities after starting SeD diet were monitored. Postweaning (4-week-old or older) start of SeD diet gives relatively older (> 8-week-old) SeD mice. The same procedure which was reported for a Se-deficient rat model (Matsumoto et al., Biol. Pharm. Bull. 23, 641–644, 2000.) could not prepared Se-deficient mouse model due to neonatal death. Starting SeD diet to the mother mouse from 2 weeks after giving birth could give 8-week-old SeD mouse model (SeD-trial-2w). Tissue GSH-Px activities of 8-week-old SeD-trial-2w group were almost non, while the normal group (fed on normal diet, MB-1) and SeC group (fed on SeD diet+1.5 mg Se in drinking water) could keep GSH-Px activity. This SeD-trial-2w mouse model can be proposed for an H 2 O 2 -induced oxidative stress model for future experiments. [ABSTRACT FROM AUTHOR]

Nano-geometry of hydroxyl radical ( • OH) generation in water caused by heavy-ion beam irradiation was evaluated using a fluorescent probe, disodium terephthalate (TPA-Na). Since • OH is recognized as a primary product in biological effects of radiation, elimination of • OH may be important to regulate the side effect of radiation therapy. Recently, using the electron paramagnetic resonance (EPR) spin-trapping technique, we reported that the two different types of • OH generations by ionizing radiation. In this study, linear energy transfer (LET) dependence on the density of localized • OH generation was evaluated using TPA-Na. The irradiation of heavy-ion beams was performed at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, National Institute of Radiological Sciences, Japan). Several concentrations (0.5-208 mM) of TPA-Na in aqueous solutions were irradiated with 32 Gy of a heavy-ion beam (C400, Si490 or Fe500) at several different LET. The amount of • OH adduct of TPA-Na (hTPA) thus generated was measured by fluorophotometer (Ex. 310 nm/Em. 425 nm). The relationship between molecular density of TPA-Na and hTPA generated was analyzed. The amount of hTPA generated by low-LET heavy-ion beam was increased in proportion to the molecular density of TPA-Na and reached a plateau through an unclear inflexion point. In the case of high-LET heavy-ion beam, however, another linear trend that passed through the origin was again observed when TPA-Na density was extremely high (TPA-Na conc.: 156-208 mM). The linear increasing trend observed at high TPA-Na density suggested an extremely dense • OH generation. [ABSTRACT FROM AUTHOR]

Radiation therapy is a cancer treatment in which a high-energy radiation is used to kill cancer cells. The production of hydroxyl radicals and other diffusible radicals is a principal cause of radiation damage to cancer. However, normal cells are affected by radiation therapy as well, and this accounts for the adverse side effects observed in this type of treatment. Antioxidants exhibit an ability to reduce free radicals generated by radiotherapy, and thereby decrease the effectiveness of the therapy in cancer cells. If the radical scavenging activity of antioxidants is inhibited in cancer cells, they can be used in combination with radiation cancer therapy to reduce the adverse side effects. In this study, we designed a quercetin derivative, whose radical scavenging activity was decreased under acidic conditions such as caner cells. The synthesis and radical scavenging activity of the quercetin derivative will be presented. [ABSTRACT FROM AUTHOR]