Tea catechins protect against lead-induced cytotoxicity, lipid peroxidation, and membrane fluidity in HepG2 cells.

Recent studies have shown that lead causes oxidative stress by inducing the generation of reactive oxygen species (ROS) and reducing the antioxidant defense system of cells. This suggests that antioxidants may play an important role in the treatment of lead poisoning as a kind of excellent scavenger of free radicals and chelator of heavy metal. Whether tea catechins have protective effects against oxidative stress after lead treatment in cell systems remains unclear. The present study was designed to elucidate if tea catechins have any protective effects on lipid peroxidation damage in lead-exposed HepG2 cells. Exposure of HepG2 cells to Pb(++) decreased cell viability and stimulated lipid peroxidation of cell membranes as measured by the thioburbituric acid reaction. Electron spin resonance (ESR) spin-labeling studies indicated that lead exposure could decrease the fluidity in the polar surface of cell membranes. Tea catechin treatment significantly increased cell viability, decreased lipid peroxidation levels, and protected cell membrane fluidity in lead-exposed HepG2 cells in a concentration-dependent manner. The galloylated catechins showed a stronger effect than nongalloylated catechins. Cotreatment with (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG) showed a synergistically protective effect. The results suggest that tea catechin supplementation may have a role to play in modulating oxidative stress in lead-exposed HepG2 cells.     

The effect of green, black and white tea on the level of alpha and gamma tocopherols in free radical-induced oxidative damage of human red blood cells

The present study was undertaken to investigate the effect of aqueous tea extracts on lipid peroxidation and alpha and gamma tocopherols concentration in the oxidative damage of human red blood cells (RBC). RBC was taken as the model for study of the oxidative damage was induced by cumene hydroperoxide (cumOOH). The antioxidative property of leaf green tea, leaf and granulate of black tea and white tea at levels 1, 2, 4 g/150 mL of water were evaluated. The correlation was observed between reducing power of tea extract and formation of malondialdehyde--MDA (an indicator of lipid peroxidation) in oxidative damage of RBC. All tea extracts at level of 4 g/150 mL of water significantly decreased concentration of MDA. The extract of green tea in comparison to black and white tea extracts at the same levels seems to be a better protective agent against oxidative stress. The antioxidant synergism between components extracted from leaves of green tea and endogenous alpha tocopherol in the oxidative damage of red blood cells was observed. The consumption of alpha tocopherol in oxidative damage of RBC was the lowest after treatment with the highest dose of green tea extract. All tea extracts did not protect against decrease of gamma tocopherol in human erythrocytes treated with cumOOH.     

In vitro protection of reactive oxygen species-induced degradation of lipids, proteins and 2-deoxyribose by tea catechins.

Both the anti- and pro-oxidant effects of tea catechins, have been implicated in the alterations of cellular functions which determine their chemoprotective and therapeutic potentials in toxicity and diseases. Here, we have studied the protective mechanism (s) of three main green tea catechins namely, epicatechin (EC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) on free radical induced oxidative degradation of membrane lipids and proteins under in vitro conditions using isolated cell free fractions from rat liver. In addition, we have also studied the effects of the tea catechins on 2-deoxyribose degradation in the presence of Fenton and Haber-Weiss oxidants. Glutathione S-transferase and cytochrome P450 2E1 activities and lipid peroxidation were found to be markedly inhibited by tea catechins. These catechins also inhibited the reactive oxygen species formation and oxidative carbonylation of subcellular proteins induced by a physiological oxidant, 4-hydroxynonenal. EGCG and the other catechins showed a time and concentration-dependent effects on the degradation of 2-deoxyribose in the presence of Fenton oxidants. Our results indicate that tea catechins prevent molecular degradation in oxidative stress conditions by directly altering the subcellular ROS production, glutathione metabolism and cytochrome P450 2E1 activity. These results may have implications in determining the chemotherapeutic use of tea catechins in oxidative stress related diseases.     

The Pyridoindole Antioxidant Stobadine Prevents Alloxan-Induced Lipid Peroxidation by Inhibiting its Propagation

Abstract: Under in vitro conditions, the pyridoindole stobadine inhibited alloxan-induced lipid peroxidation in a model biological membrane with the efficacy comparable with that of the standard Trolox. Intermediary alloxan radicals and hydroxyl radicals were not directly involved in the process of lipid peroxidation, however, the presence of iron chelate was a necessary prerequisite. Since stobadine did not affect the kinetics of alloxan redox-cycling in the presence of GSH, we suggest that the protective action of stobadine against the alloxan-induced lipid peroxidation was mediated predominantly by its ability to quench peroxyl radicals, inhibiting thus the propagation stage of the oxidative damage. The results also indicate that toxic effects of alloxan may well be mediated by mechanism(s) not involving hydroxyl radicals.     

Protective effects of epigallocatechin gallate following 3-nitropropionic acid-induced brain damage: possible nitric oxide mechanisms

Introduction

The role of oxidative stress has been well known in neurodegenerative disorders. 3-Nitropropionic acid (3-NP) is a plant-based mycotoxin that produces HD like symptoms in animals. Oxidative stress and nitric oxide mechanisms have been recently proposed in the 3-NP-induced neurotoxicity. Epigallocatechin gallate (EGCG) is one of the major components of green tea, known for its potent antioxidant activity. Besides, neuroprotective effect of EGCG has also been suggested in different experimental models.

Objectives

The present study has been designed to examine possible effect of EGCG against 3-NP induced behavioral, oxidative stress, mitochondrial dysfunction, and striatal damage in rats and its possible interaction with nitric oxide modulators.

Material and methods

Systemic 3-NP (10 mg/kg) administration for 14 days significantly reduced locomotor activity, body weight, grip strength, oxidative defense (raised levels of lipid peroxidation, nitrite concentration, depletion of antioxidant enzyme), and mitochondrial enzymes activity in striatum, cortex, and hippocampal regions of the brain.

Results

Fourteen days of EGCG pretreatment (10, 20, and 40 mg/kg) significantly attenuated behavioral alterations, oxidative damage, mitochondrial complex enzymes dysfunction, and striatal damage in 3-NP-treated animals. l-arginine (50 mg/kg) pretreatment with sub-effective dose of EGCG (20 mg/kg) significantly reversed the protective behavioral, biochemical, cellular, and histological effects of EGCG. However, l-NAME (10 mg/kg) pretreatment with EGCG (20 mg/kg) significantly potentiated the protective effect of EGCG which was significant as compared to their effect per se.

Conclusion

The present study shows that EGCG attenuate 3-NP-induced neurotoxicity, and nitric oxide modulation might be involved in its protective action.     

Characterization of the acetaminophen-induced degradation of cytochrome P450-3A4 and the proteolytic pathway

This study compared the in vitro responses of malignant and normal cells from the human oral cavity to tea extracts and to its main polyphenolic component, (-)-epigallocatechin gallate (EGCG). The antiproliferative effects of tea polyphenolic extracts and EGCG were more pronounced towards immortalized, tumourigenic (CAL27, HSC-2, and HSG(1)) and non-tumourigenic (S-G) cells than towards normal (GN56 and HGF-1) fibroblasts and green tea was more toxic than black tea. As the addition of tea extract or EGCG to cell culture medium led to the formation of hydrogen peroxide (H(2)O(2)), the research then focused on EGCG as an inducer of oxidative stress, using CAL27, the cancerous cells most sensitive to EGCG, HSG(1), the cancerous cells least sensitive to EGCG, and GN56 cells. The toxicity of EGCG was decreased in the presence of catalase, an enzyme that degrades H(2)O(2), or of deferoxamine, a chelator of Fe(3+). Conversely, pretreatment of the cells with the glutathione depleters, 1-chloro-2,4-dinitrobenzene and 1,3-bis(2-chloroethyl)-N-nitrosourea, potentiated the toxicity of EGCG. A 4-hr exposure to EGCG lessened the intracellular level of reduced glutathione in the CAL27 and HSG(1) cells, but not in the GN56 fibroblasts. Whereas EGCG itself did not induce lipid peroxidation, Fe(2+)-induced lipid peroxidation was potentiated by EGCG. A 72-hr exposure to cytotoxic concentrations of EGCG induced significant cytoplasmic vacuolization in all cell types. The results presented herein are consistent with EGCG acting as a prooxidant, with the cancerous cells more sensitive to oxidative stress than the normal cells.     

Epigallocatechin-3-gallate attenuates acrylamide-induced apoptosis and astrogliosis in rat cerebral cortex

The potent neurotoxic agent acrylamide (ACR) is formed during Maillard reaction in food processing. Epigallocatechin-3-gallate (EGCG), a major bioactive component of green tea, is an antioxidant, but its effects on ACR-induced neurotoxicity are unclear. Here, we investigated the neuroprotective effects of EGCG against ACR-induced apoptosis and astrogliosis in the cerebral cortex. Rats were pretreated with EGCG for 4 d and then co-administered ACR for 14 d. Immunohistochemical analysis of glial fibrillary acidic protein and 8-hydroxy-2′-deoxyguanosine indicated that EGCG attenuated astrogliosis and DNA damage in ACR-treated rats. Analysis of DNA fragmentation and protein expression of Bax, Bcl-2, caspase 3, and cytochrome c revealed that EGCG inhibited ACR-induced apoptosis. Furthermore, EGCG inhibited oxidative stress by enhancing the activity of antioxidant enzymes and glutathione levels and reducing the formation of reactive oxygen species and lipid peroxidation. Taken together, our data demonstrate that EGCG inhibits ACR-induced apoptosis and astrogliosis in the cerebral cortex.     

Epigallocatechin gallate, a constituent of green tea, regulates high glucose-induced apoptosis

A high concentration of glucose has been implicated as a causal factor in initiation and progression of diabetic complications, and there is evidence to suggest that hyperglycemia increases the production of free radicals and oxidative stress. Therefore, compounds that scavenge reactive oxygen species may confer regulatory effects on high glucose-induced apoptosis. Epigallocatechin gallate (EGCG), the major polyphenolic of green tea, is reported to have an antioxidant activity. We investigated the effect of EGCG on high glucose-induced apoptosis in U937 cells. Upon exposure to 35 mM glucose for 2 days, there was a distinct difference between untreated cells and cells pre-treated with 1 μM EGCG for 2 h in regard to cellular redox status and oxidative DNA damage to cells. EGCG pre-treated cells showed significant suppression of apoptotic features such as DNA fragmentation, damage to mitochondrial function, and modulation of apoptotic marker proteins upon exposure to high glucose. This study indicates that EGCG may play an important role in regulating the apoptosis induced by high glucose presumably through scavenging of reactive oxygen species.     

康力欣胶囊联合甘露聚糖肽治疗肝癌的临床研究

目的探讨康力欣胶囊联合甘露聚糖肽治疗肝癌的临床疗效。方法选取2014年2月—2015年7月在玉溪市人民医院肿瘤科接受治疗的肝癌患者86例,分成对照组(43例)和治疗组(43例)。所有患者均给予必要的化疗和碘油栓塞治疗,1次/周,连续治疗2周。对照组在此基础上静脉滴注甘露聚糖肽注射液,10 mg加入250 mL生理盐水,1次/d。治疗组在对照组基础上口服康力欣胶囊,3粒/次,3次/d。两组患者均连续治疗4周。观察两组的临床疗效,同时比较两组生存质量、免疫功能和血清基质金属蛋白酶水平改善情况。结果治疗后,对照组客观缓解率(ORR)为41.86%,临床获益率(CBR)为74.42%;治疗组ORR为65.12%,CBR为90.70%,两组ORR、CBR比较差异具有统计学意义(P0.05)。治疗后,对照组与治疗组患者生存质量改善率分别为74.42%和93.02%,两组差异比较具有统计学意义(P0.05)。治疗后,两组CD~(3+)、CD~(4+)和CD~(4+)/CD~(8+)上升,差异有统计学意义(P0.05);且治疗组变化的更显著(P0.05)。治疗后,两组血清基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)水平均较同组治疗前明显降低(P0.05);与对照组相比,治疗组降低的更显著(P0.05)。结论康力欣胶囊联合甘露聚糖肽治疗肝细胞癌具有很好的临床疗效,可以提高患者免疫能力及改善生活质量,具有一定的临床应用推广价值。     

表没食子儿茶素没食子酸酯抗氧化作用机制的研究进展

表没食子儿茶素没食子酸酯(EGCG)是绿茶中的主要儿茶素,大量研究表明绿茶在治疗严重慢性疾病如心血管病、神经退行性病变、肿瘤、代谢综合征、2型糖尿病等方面发挥了积极的生物学作用。绿茶的这种保护性作用主要归因于EGCG强有力的抗氧化活性。EGCG的抗氧化作用机制主要包括清除自由基、金属螯合、抑制细胞信号转导通路、调节氧化和抗氧化酶系等。综述了其抗氧化机制的研究进展,以期为临床应用及开发相同或相似机制的药物提供理论依据。     

表没食子儿茶素没食子酸酯抗肿瘤作用机制的研究进展

绿茶中的活性成分已经被证明具有预防和控制癌症的作用,其中表没食子儿茶素没食子酸酯（EGCG）抗癌活性最高。EGCG能够通过调控氧化应激、阻滞肿瘤细胞周期、抑制肿瘤血管形成、诱导肿瘤细胞凋亡等途径实现抗肿瘤效果。因此对EGCG抗肿瘤作用机制的进行了综述,以期为EGCG的临床应用提供参考。     

Evaluation of the protective effect of Ilex paraguariensis and Camellia sinensis extracts on the prevention of oxidative damage caused by ultraviolet radiation

We evaluated the effects green and mate teas on oxidative and DNA damages in rats exposed to ultraviolet radiation. Were utilized 70 adult male Wistar rats that received daily oral or topic green or mate tea treatment during exposed to radiation by seven days. After, animals were killed by decapitation. Thiobarbituric acid-reactive species levels, protein oxidative damage were evaluated in skin and DNA damage in blood. Our results show that the rats exposed to ultraviolet radiation presented DNA damage in blood and increased protein carbonylation and lipid peroxidation in skin. Oral and topic treatment with green tea and mate tea prevented lipid peroxidation, both treatments with mate tea also prevented DNA damage. However, only topic treatment with green tea and mate tea prevented increases in protein carbonylation. Our findings contribute to elucidate the beneficial effects of green tea and mate tea, here in demonstrated by the antioxidant and antigenotoxic properties presented by these teas.     

Epigallocatechin-3-gallate protects rat brain mitochondria against cadmium-induced damage

Many health claims have been made about the medicinal benefits of drinking green tea, including neuroprotection. This study mainly focuses on Epigallocatechin 3-gallate (EGCG), a potent antioxidant, which is abundantly found in green tea. Cadmium [Cd²⁺] is a toxic pollutant that leads to neurotoxicity in both animals and humans. Although the entrance of Cd²⁺ in the adult central nervous system is limited, developmental neurotoxicity has been evidenced as result of the blood-brain barrier (BBB) immaturity. Moreover, high Cd²⁺ levels are known to impair BBB function. Furthermore, the molecular mechanisms related to its neurotoxic properties remain unknown. This study evaluates the potential protective effect of the major green tea polyphenol, EGCG, against Cd²⁺-induced mitotoxicity under in vitro conditions, using mitochondrial-enriched fractions from rat brain. Co-incubation of EGCG with Cd²⁺ prevented the Cd²⁺-induced mitochondrial dysfunction (capacity to reduce MTT to formazan). In addition, EGCG completely prevented mitochondrial lipid peroxidation induced by Cd²⁺ but did not affect non protein thiols levels. Spectroscopic studies have shown EGCG able to form a chemical complex with Cd²⁺, in an equimolar ratio. In this study we demonstrate EGCG effectiveness in protecting against Cd²⁺-induced mitochondrial dysfunction and lipid peroxidation probably due to its antioxidant and chelating effects.     

Antioxidant activity of the monoamine oxidase B inhibitor lazabemide

Free radical-induced damage to lipid and protein constituents of neuronal membranes contributes to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). The development of an effective inhibitor of oxidative stress represents an important goal for the treatment of AD. In this study, the intrinsic antioxidant activity of lazabemide, a potent and reversible inhibitor of monoamine oxidase B (MAO-B), was tested in a membrane-based model of oxidative stress. Under physiologic-like conditions, lazabemide inhibited lipid peroxidation in a highly concentration-dependent manner. At low, pharmacologic levels of lazabemide (100.0 nM), there was a significant (P < 0.001) and catalytic reduction in lipid peroxide formation, as compared with control samples. The antioxidant activity of lazabemide was significantly more effective than that of either vitamin E or the MAO-B inhibitor, selegiline. The ability of lazabemide to inhibit oxidative damage is attributed to physico-chemical interactions with the membrane lipid bilayer, as determined by small angle x-ray diffraction methods. By partitioning into the membrane hydrocarbon core, lazabemide can inhibit the propagation of free radicals by electron-donating and resonance-stabilization mechanisms. These findings indicate that lazabemide is a potent and concentration-dependent inhibitor of membrane oxy-radical damage as a result of inhibiting membrane lipid peroxidation, independent of MAO-B interactions.     

Hepatotoxicity of high oral dose (−)-epigallocatechin-3-gallate in mice

The tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) has been studied for chronic disease preventive effects, and is marketed as part of many dietary supplements. However, case-reports have associated the use of green tea-based supplements with liver toxicity. We studied the hepatotoxic effects of high dose EGCG in male CF-1 mice. A single dose of EGCG (1500 mg/kg, i.g.) increased plasma alanine aminotransferase (ALT) by 138-fold and reduced survival by 85%. Once-daily dosing with EGCG increased hepatotoxic response. Plasma ALT levels were increased 184-fold following two once-daily doses of 750 mg/kg, i.g. EGCG. Moderate to severe hepatic necrosis was observed following treatment with EGCG. EGCG hepatotoxicity was associated with oxidative stress including increased hepatic lipid peroxidation (5-fold increase), plasma 8-isoprostane (9.5-fold increase) and increased hepatic metallothionein and γ-histone 2AX protein expression. EGCG also increased plasma interleukin-6 and monocyte chemoattractant protein-1. Our results indicate that higher bolus doses of EGCG are hepatotoxic to mice. Further studies on the dose-dependent hepatotoxic effects of EGCG and the underlying mechanisms are important given the increasing use of green tea dietary supplements, which may deliver much higher plasma and tissue concentrations of EGCG than tea beverages.     

Evaluation of epigallocatechin gallate and epicatechin gallate effects on acrylamide-induced neurotoxicity in rats and cytotoxicity in PC 12 cells

The neurotoxicity of acrylamide (ACR) monomer occurs through different mechanisms such as oxidative stress. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) are green tea catechins which are known as powerful antioxidants. In this study, we examined the possible protective effects of ECG and EGCG on ACR neurotoxicity in both in-vitro and in-vivo models. PC12 cells were exposed to different concentrations of ECG and EGCG. After 24 and 48?hours, ACR was added to the cells (IC₅₀?=?4.85?mM) and cell viability was measured through MTT assay after 24?hours. Male Wistar rats were pretreated with ECG, EGCG (10, 20 and 40?mg/kg, i.p) and vitamin E (200?IU/kg i.p.) for 3?days. Afterwards they were treated with ACR (50?mg/kg, i.p.) for 11?days. After the treatment period, gait score examination was performed and molondialdehyde (MDA) and reduced glutathione (GSH) were measured in cerebral cortex. ACR reduced the cell viability in a concentration-dependent manner. Both ECG and EGCG (20?μM) showed inhibitory effects on ACR cytotoxicity. ACR significantly induced gait abnormalities, decreased GSH level and increased lipid peroxidation in cerebral cortex. ECG and EGCG (20?mg/kg) improved all ACR toxic effects. Although the food intake was increased in pretreated groups compared to the ACR-treated group, intensive weight loss was observed due to the green tea’s different weight loss mechanisms. ECG and EGCG inhibited the cytotoxicity of ACR in PC12 cells and increased GSH level and decreased lipid peroxidation in rat cerebral cortex.     

Green tea protection against age-dependent ethanol-induced oxidative stress

Ethanol intoxication leads to oxidative stress, which may be additionally enhanced by aging. The aim of this study was to investigate the influence of green tea as a source of water-soluble antioxidants on the ability to prevent oxidative stress in aged rats sub-chronically intoxicated with ethanol. Two-, 12-, and 24-mo-old male Wistar rats were divided into 4 experimental groups: (1) control, (2) green tea, (3) ethanol, and (4) ethanol and green tea. Ethanol intoxication produced age-dependent decrease in the activity of serum superoxide dismutase, glutathione peroxidase, and reductase and in levels of glutathione (GSH), vitamins C, E, and A, and beta-carotene. Changes in the serum antioxidative ability were accompanied by enhanced oxidative modification of lipid (increase in lipid hydroperoxides, malondiadehyde, and 4-hydroxynonenal levels) and protein (rise in carbonyl group levels). Green tea partially protected against changes in antioxidant enzymatic as well as nonenzymatic parameters produced by ethanol and enhanced by aging. Administration of green tea significantly protects cellular components such as lipids and proteins against oxidative modification. Results indicate that green tea effectively protects blood serum against oxidative stress produced by ethanol as well as aging.     

Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin

Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been shown to produce oxidative damage to membrane lipids in the brain. In this study, we investigated the effect of protracted social isolation stress on lipid peroxidation activity in the mouse brain and elucidated the protective effect of majonoside-R2, a major saponin component of Vietnamese ginseng, in mice exposed to social isolation stress. Thiobarbituric acid reactive substance levels, one of the end products of lipid peroxidation reaction, were increased in the brains of mice subjected to 6-8 weeks of social isolation stress. Measurements of nitric oxide (NO) metabolites (NO(x)(-)) also revealed a significant increase of NO production in the brains of socially isolated mice. Moreover, the depletion of brain glutathione content, an endogenous antioxidant, in socially isolated animals occurred in association with the rise in lipid peroxidation. The intraperitoneal administration of majonoside-R2 (10-50 mg/kg) had no effect on thiobarbituric acid reactive substances (TBARS), NO, or glutathione levels in the brains of group-housed control mice but it significantly suppressed the increase in TBARS and NO levels and the decrease in glutathione levels caused by social isolation stress. These results suggest that mice subjected to 6-8 weeks of social isolation stress produces oxidative damage in the brain partly via enhancement of NO production, and that majonoside-R2 exerts a protective effect by modulating NO and glutathione systems in the brain.     

Enhancement of antioxidant defense system by epigallocatechin-3-gallate during bleomycin induced experimental pulmonary fibrosis

Oxidative stress resulting from an imbalance between radical-generating and radical scavenging systems plays an important role in the pathogenesis of pulmonary fibrosis. Epigallocatechin-3-gallate (EGCG), a polyphenol and a major component of green tea, possess a potent antioxidant property. This study was designed to evaluate the potential antioxidative activity of EGCG in the plasma and lungs during bleomycin induced experimental pulmonary fibrosis. Intratracheal administration of bleomycin (6.5 U/kg body weight) to rats resulted in significant reduction of body weight, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Elevations in lung W/D (wet weight/dry weight) ratio, hydroxyproline content was observed with a synchronized increase in lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides). Intraperitoneal administration of EGCG at a dose of 20 mg/kg body weight significantly improved the body weight, enzymic and non enzymic antioxidants and considerably decreased the W/D ratio, hydroxyproline and lipid peroxidation marker levels. Histological observations also correlated with the biochemical parameters. Thus, this study confirms the beneficial use of EGCG in alleviating the oxidative stress induced during pulmonary fibrosis.     

Antioxidative constituents fromPaeonia lactiflora

The ethanol extract of the peony root (Paeonia Lactiflora Pall, Paeoniaceae) as well as its major active components including gallic acid and methyl gallate were evaluated for their protective effects against free radical generation and lipid peroxidation. In addition, the protective effects against hydrogen peroxide-induced oxidative DNA damage in a mammalian cell line were examined. The ethanol extracts of the peony root (PREs) and its active constituents, gallic acid and methyl gallate, exhibited a significant free radical scavenging effect against 1,1-diphenyl-2-picryl hydrazine (DPPH) radical generation and had an inhibitory effect on lipid peroxidation, as measured by the level of malondialdehyde (MDA) formation. The PREs did not have any pro-oxidant effect. They strongly inhibited the hydrogen peroxide-induced DNA damage from NIH/3T3 fibroblasts, as assessed by single cell gel electrophoresis. Furthermore, the oral administration of 50% PRE (50% ethanol extract of peony root), gallic acid and methyl gallate potently inhibited the formation of micronucleated reticulocytes (MNRET) in the mouse peripheral blood induced by a KBrO3 treatment in vivo. Therefore, PREs containing gallic acid and methyl gallate may be a useful antigenotoxic antioxidant by scavenging free radicals, inhibiting lipid peroxidation and protecting against oxidative DNA damage without exhibiting any pro-oxidant effect.