Protective Effect of Phenolic Antioxidants on the Cytotoxicity Induced by Phosphatidylcholine Hydroperoxide

Phosphatidylcholine hydroperoxides show weak but distinct toxicity toward cultured human umbilical vein endothelial cells. The protective effect of phenolic antioxidants against the cytotoxicity of phosphatidylcholine hydroperoxides was examined. Probucol depressed the toxicity most effectively among the antioxidants studied under both pretreatment and concurrent treatment conditions. α-Tocopherol showed a protective effect in the case of concurrent treatment. Protection by phenolic antioxidants against the cytotoxicity of phosphatidylcholine hydroperoxides seems to depend on their incorporation rate into cells, their affinity for phospholipids, their antioxidative activity, and their orientation in membranes.     

Impact of Phenolic Antioxidants on Structural Properties of Micellar Solutions

Antioxidants solubilized in micellar solutions can change micellar properties like the size and shape of micelles, critical micellar concentration (cmc) and viscosity. Interactions arising between antioxidants and the surfactant determine the locations of antioxidants and vice versa. The location and interaction are dependent on the type of both the antioxidant and surfactant. Influences of various antioxidants on the physical and structural properties were tested in micellar systems of cationic CTAB, non-ionic Brij 58 and anionic SDS. The antioxidants used to investigate the effects of gradually increasing lipophilicity were gallic acid (GA) and the gallate esters from methyl to octyl gallate (MG-OG). Hydroxy cinnamic acids (HCAs) like -coumaric acid (pC), caffeic acid (CA), ferulic acid (FA) and sinapic acid (SA) were employed to observe effects of functional groups like hydroxyl and methoxy groups. Micellar size and shape determined by small angle neutron scattering (SANS), viscosity and cmc were chosen to characterize the antioxidant influence. In Brij 58 systems propyl gallate (PG) did not affect the cmc or aggregation number but decreased micellar size slightly due to an intercalation of PG into the region of the polyoxyethylene chain and the first adjacent alkyl chain methylene groups. In SDS systems the micellar size and cmc decreased in the presence of PG. This was attributed to PG residing in the Stern layer. However, in CTAB systems micelles swelled at low PG concentration and in the presence of GA, while higher PG concentrations and more lipophilic antioxidants led to a sphere-to-rod transition with a simultaneous increase in viscosity and decrease in cmc. This revealed the intercalation of antioxidants in the palisade layer of CTAB micelles entering into strong interactions of electrostatic and hydrophobic origin. It could be demonstrated that the interactions became stronger the more lipophil an antioxidant is and the more hydroxyl groups are attached to the aromatic ring. Differences in the location and interaction of antioxidant and micelles are proposed as being responsible for the effectiveness of antioxidants.     

酚类抗氧化剂对Maillard反应的影响及其作用机制

Maillard反应是食品加工和贮藏过程中发生的重要而最复杂的反应,在食品风味物质形成中发挥积极作用,但近二三十年来的研究也发现它可能存在的食品安全隐患。Maillard反应受氨基和羰基物质组成的影响,但其他物质对Maillard反应的干扰作用研究不多。本文综述了Maillard反应过程中抗氧化活性物质和自由基形成的特点,以及外源酚类可能在丙烯酰胺、呋喃、羟甲基糠醛等有害物质形成中发生的作用;在此基础上,提出了今后应研究的科学问题。     

Conversion of Nitroxide Radicals by Phenolic and Thiol Antioxidants

Nitrone/nitroso spin traps are often used for detection of unstable hydroxyl radical giving stable nitroxide radicals with characteristic electron spin resonance (ESR) signals. This technique may be useful only when the nitroxide radicals are kept stable in the reaction system. The aim of the present study is to clarify whether the nitroxide radicals are kept stable in the presence of the hydroxyl radical scavengers. Effect of hydroxyl radical scavengers on the ESR signals of nitroxide radicals, 2,2,6,6-tetramethyI-piperi-dine-N-oxyl (TEMPO) and the spin adduct (DMPO-OH) of 5,5-dimethyl-l-pyrroline N-oxide (DMPO) and hydroxyl radical, was examined. Although the ESR signals of TEMPO and the DMPO-OH spin adduct were unchanged on treatment with ethanol and dimethyl sulfoxide, their intensities were effectively decreased on treatment with 6-hydroxy-2,5,7,8-tetra-methylchroman-2-carboxylic acid (Trolox), cysteine, glutathione, 2-mercaptoethanol and metallothionein. Hence, the results of the detection of hydroxyl radical in the presence of phenolic and thiol antioxidants by the ESR technique using nitrone/nitroso spin traps may be unreliable.     

Mechanisms of Redox Regulation of Chemoresistance in Tumor Cells by Phenolic Antioxidants

Effects of water-soluble sulfur-containing phenolic antioxidants sodium 3-(3′-tert-butyl-4′- hydroxyphenyl)propyl thiosulfonate and potassium 3,5-dimethyl-4-hydroxybenzyl thioethanoate on chemoresistance in tumor cells have been studied. The studied phenolic antioxidants cause oppositely directed changes in the redox properties and chemoresistance in tumor cells. Potassium 3,5-dimethyl-4-hydroxybenzyl thioethanoate increases redox buffering capacity and doxorubicin resistance in tumor cells. Sodium 3-(3′- tert-butyl-4′-hydroxyphenyl)propyl thiosulfonate reduces the redox buffering capacity, which leads to a decrease in the chemoresistance of tumor cells. These observations suggest that one of the key mechanisms responsible for the formation of tumor cell resistance to antitumor compounds is the attenuation of apoptosis through increase of redox buffering capacity. The dependence of protein sensor redox state on oxidant concentrations and on redox buffering capacity in cells has been determined based on the proposed biophysical model of redox-dependent mechanism of apoptosis activation.     

Antioxidants from Steamed Used Tea Leaves and Their Reaction Behavior

The most efficient steaming conditions below 200 °C for extracting antioxidants from used tea leaves and their reaction behavior during the steaming treatment were investigated. The antioxidative activity of the steamed extracts increased with increasing steaming temperature, and the yield of the ethyl acetate extract fraction from each steamed extract showing the greatest antioxidative activity also increased. Caffeine, (?)-catechin, (?)-epicatechin, (?)-gallocatechin, (?)-epigallocatechin, (?)-catechin gallate, (?)-epicatechin gallate, (?)-gallocatechin gallate, (?)-epigallocatechin gallate and gallic acid were identified from the ethyl acetate extract fraction. Quantitative analyses demonstrated that the catechins with a 2,3-cis configuration decreased with increasing steaming temperature, whereas the corresponding epimers at the C-2 position increased. Each pair of epimers showed similar antioxidative activity to each other, indicating that the epimerization reaction did not contribute to the improved antioxidative activity. It is concluded from these results that the improvement in antioxidative activity at higher steaming temperatures was due to the increased yield of catechins and other antioxidants.     

Inhibition of Peroxynitrite-Mediated Oxidation of Dopamine by Flavonoid and Phenolic Antioxidants and Their Structural Relationships

The interaction between peroxynitrite and dopamine and the inhibition of this reaction by plant-derived antioxidants have been investigated. Peroxynitrite promoted the oxidation of dopamine to 6-hydroxyindole-5-one as characterised by HPLC and photodiode array spectra, akin to the products of the tyrosinase-dopamine reaction, but no evidence of dopamine nitration was obtained. Although peroxynitrite did not cause nitration of dopamine in vitro, the catecholamine is capable of inhibiting the formation of 3-nitrotyrosine from peroxynitrite-mediated nitration of tyrosine. The plant-derived phenolic compounds, caffeic acid and catechin, inhibited peroxynitrite-mediated oxidation of dopamine. This effect is attributed to the ability of catechol-containing antioxidants to reduce peroxynitrite through electron donation, resulting in their oxidation to the corresponding o-quinones. The antioxidant effect of caffeic acid and catechin was comparable to that of the endogenous antioxidant, glutathione. In contrast, the structurally related monohydroxylated hydroxycinnamates, p-coumaric acid and ferulic acid, which inhibit tyrosine nitration through a mechanism of competitive nitration, did not inhibit peroxynitrite-induced dopamine oxidation. The findings of the present study suggest that certain plant-derived phenolics can inhibit dopamine oxidation.     

抗氧化剂对脂质过氧化反应混合物引起人培养细胞DNA损伤的影响

 <正> 脂质过氧化反应(LPR)中产生的自由基和过氧化物可引起多种细胞损伤,特别是对DNA的损伤可能是许多癌肿的重要原因。Akasaka等将E.coli与鼠肝微粒体脂质过氧化反应混合物(LPRM)孵育,使有DNA修复缺陷的细菌株突变率增加。我们将人羊膜FL细胞与大鼠肝微粒体LPRM共同培养,看能否诱发程序外DNA合成(UDS),并分组加入抗氧化剂观察其影响。     

Study on Soybean Lipoxygenase

Some β-bisabolene derivatives, III, XX, XXVII and XXVIII, were synthesized and shown to possess the juvenile hormone activity.     

Effect of Antioxidants on Ammonia Induced Cns-Renal Pathobiology in Sheep

The effect of antioxidants on ammonia induced CNS and renal pathobiology in 10 sheep infested by L. Cuprina larvae was investigated. The condition produces severe dermatitis, proliferation of macro-phages and hyperammonaemia, and free radicals may therefore be involved in the pathogenesis. Five of the sheep (treated group) were given daily intramuscular (im) injections of 2 g sodium ascorbate, 5.9 g dl-alpha tocopherol (11 days) and 3 g desferrioxamine mesylate (6 days) with 70 mg oral butylated-hydroxyanisole (11 days). The treatment prevented rises in jugular ammonia, creatinine, urea, sodium and pH, and decreases in water intake, urine output and glucose. The findings showed that antioxidants prevented ammonia induced CNS and renal pathobiology and suggest that free radicals contribute to the pathogenesis of the condition.     

Protective Effects of Exogenous Antioxidants and Phenolic Compounds on Photosynthesis of Wheat Leaves under High Irradiance and Oxidative Stress

Infiltration of methyl viologen (MV, source of O₂ ^–) and Na-diethyldithiocarbamate (DDC, inhibitor of SOD) into wheat leaves resulted in the accumulation of active oxygen species and photo-oxidative damage to photosynthetic apparatus under both moderate and high irradiance. Exogenous antioxidants, ascorbate (ASA) and mannitol, scavenged active oxygen efficiently, protected the photosynthetic system from MV and DDC induced oxidative damage, and maintained high F_v/F_m [maximal photochemical efficiency of photosystem 2 (PS2) while all PS2 reaction centres are open], F_m/F₀ (another expression for the maximal photochemical efficiency of PS2), _PS2 (actual quantum yield of PS2 under actinic irradiation), q_P (photochemical quenching coefficient), P _N (net photosynthetic rate), and lowered q_NP (non-photochemical quenching coefficient) of the leaves kept under high irradiance and oxidative stress. Phenolic compounds used in these experiments, catechol (Cat), resorcinol (Res), and tannic acid (Tan), had similar anti-oxidative activity and protective effect on photosynthetic apparatus as ASA and mannitol. The anti-oxidative activity and the protective effect of phenolic compounds increased with increase in their concentration from 100 to 300 g m^–3. The number and the position of hydroxyl group in phenolic molecules seemed to influence their antioxidative activity.     

Anabolic Effect of Natural and Synthetic Antioxidants

The order of responses of cell systems of organs and the changes in the content of some proteins in mouse and dog blood in response to addition of natural (-tocopherol) and synthetic (ionol) antioxidants was studied at the whole-body level using ERP spectroscopy, radioisotope analysis, and chemiluminescence technique. Responses were evaluated by the temporary and concentration-dependent changes in the activity of ribonucleotide reductase and the rate of protein and DNA synthesis in organs of the mouse, as well as by the changes in the pools of Fe³⁺-transferrin and Cu²⁺-ceruloplasmin in blood and the antiradical activity of blood plasma of the dog and mouse. During the first 24 h of exposure to -tocopherol, the activity ribonucleotide reductase in the bone marrow rapidly increased, whereas the activity of this enzyme and the rate of DNA synthesis in the thymus and spleen were suppressed by 30–50% compared to the control. The changes in these parameters had a phase mode with maxima on days 2–3 and 6–8. The stimulatory effect of the antioxidant on the processes of synthesis was concentration-dependent. We found that the optimal stimulation of the synthesis of deoxyribonucleotides, DNA, and protein was achieved by single administration of -tocopherol at a dose of 20 mg per dog with an average weight of 15 kg and 17 mg/kg in the case of mice. Single or repeated administration of higher doses of -tocopherol was either ineffective or even suppressed the synthesis of DNA and deoxyribonucleotides. Ionol administered at a dose of 60 mg/kg increased DNA and protein synthesis in mouse organs 2–4 and 1.2–1.5 times, respectively, compared to the control. It was also shown that single and repeated administration of -tocopherol to dogs increased the pool of Fe³⁺-transferrin and Cu²⁺-ceruloplasmin in blood 2–3 times and by 20–30%, respectively, compared to the control. It is suggested to use changes in Fe³⁺-transferrin pool in peripheral blood for evaluation of the stimulatory effect of antioxidants on the synthesis of macromolecules in organs and for the determination of dependence of this effect on the concentration of antioxidants.     

抗氧化剂对皮肤角质细胞体外寿命的影响

考察了抗氧化剂对鼠角质细胞体外培养寿命的影响。实验发现在角质细胞的体外培养过程中添加抗氧化剂有利于延长细胞的寿命,其中效果最好的是巯基乙醇,其次为过氧化氢酶和SOD,但在体外培养过程中,角质细胞生长速率仍然逐渐下降。实验还发现,添加抗氧化剂可在一定程度上提高角质细胞的克隆形成率,减缓细胞衰老速率。同时,通过考察鼠表皮角质细胞衰老动力学,获得了对应于不同抗氧化剂的细胞衰老动力学常数。      

网络抗氧化剂对大鼠非酒精性脂肪肝炎模型疗效的动态观察

目的:研究网络抗氧化荆对大鼠非酒精性脂肪肝炎的治疗效果.方法:雄性SD大鼠72只,随机分为正常对照组、模型组、网络抗氧化剂组(n=24).正常对照组喂以普通饲料,网络抗氧化剂组及模型组均予高脂饮食.网络抗氧化剂组高脂饮食同时使用维生素E(100mg/kg)、硫辛酸(40mg/kg)、辅酶Q10(100mg/kg)、维生素C(100mg/kg)、还原性谷热水胱甘肽(100mg/kg)联合灌胃治疗,1次/日.分别在8周、10周、12周通过肝功能、血脂及肝组织病理动态观察病情转归情况,检测MDA、SOD评定网络抗氧化剂在病情转归中起到的抗氧化作用.结果:网络抗氧化剂组体重、肝指数、血清ALT、AST、MDA、TC及肝组织MDA均显著低于模型组;血清、肝组织SOD显著高于模型组;病理学模型组在8-10周出现多处肝细胞内脂滴堆积,出现气球样变,且有少量炎细胞浸润,随着进食高脂饮食时间的延长病变程度逐渐加重,至12周脂肪变及炎症程度均有所加重,出现点灶状坏死、桥接坏死.甚至出现部分肝纤维化.同期网络抗氧化剂肝组织病理显示脂肪变及炎症显著轻于模型组,无明显肝纤维化出现.结论:网络抗氧化剂对NASH有较好的防治效果.     

Lipoxygenase pathways of macrophages

Resident mouse peritoneal macrophages when exposed to zymosan during the first day of cell culture synthesize and secrete large amounts of prostaglandin E2 and leukotriene (LT) C4, the respective products of cyclooxygenase- and 5-lipoxygenase-catalyzed oxygenations of arachidonic acid. Under these conditions of cell stimulation only small amounts of hydroxyeicosatetraenoic acids (HETEs) are concomitantly produced. However, exogenously added arachidonic acid is metabolized to large amounts of 12- and 15-HETE. No LTC4 is formed under these conditions. Inasmuch as 12- and 15-HETE have been shown to modulate certain lymphocyte responses, further study of the regulation of their production by macrophages is warranted.     

Reinvestigation of Phenolic Ferrier Reaction: Selective Synthesis of Aryl O-Δ2-Glycosides

Reinvestigation of the phenolic Ferrier reaction is described. Ferrier reaction between acetylglycals and phenols in toluene in the presence of a catalytic amount of Lewis acid at low temperature gave aryl O-Δ²-glycosides in moderate to good yields, but the reaction in dichloromethane resulted in the formation of aryl C-Δ²-glycosides predominantly.     

An Examination of the Effect of Three Phenolic Disinfectants on Mycobacterium tuberculosis

The effect of a phenolic disinfectant ( o -phenylphenol 45% w/w) with linseed oil soap or with soya oil soap on Mycobacterium tuberculosis was determined by three methods. Neither the geometrical dilution test nor the modified capacity use-dilution test revealed any differences between the two disinfectants. However, paradoxically both methods proved that the highest concentration of the disinfectants tested (3·5% v/v) exhibited a very low germicidal effect on M. tuberculosis , whereas lower concentrations showed a much better effect. When determining the tuberculocidal effects of various concentrations of the two disinfectants at different exposure times, the higher concentrations showed very low effects, even after the longest exposure time. At concentrations of 2·0 and 1·0% (v/v), the disinfectants displayed the most rapid effects. In the present investigation the disinfectant with the linseed oil soap seemed to destroy the cells more quickly than that with the soya oil soap. The third disinfectant containing p -chloro- m -cresol and o -benzyl- p -chlorophenol with a total of 9·2% (w/w) phenols in a detergent system, did not display, when employing the capacity use-dilution test, the same phenomenon in the concentrations used, but the experiment showed that the recommended use-dilution concentration ought to be doubled.     

抗氧化剂辅助疗法对光动力疗法疗效的影响

研究食物中含有的天然抗氧化剂对光动力疗法治疗效果的影响。通过在常规培养的K562细胞悬浮液中分别加入染料木素、鞣花酸、山竹黄酮这几种天然抗氧剂,用戊氨基乙酰丙酸-光动力疗法（ALA—PDT）作用后,检测各组细胞的存活率。研究发现染料木素、鞣花酸、山竹黄酮均可以提高光动力疗法的疗效。研究结果表明,抗氧化剂疗法和光动力疗法相互结合能够起到良好的治疗效果。     

Inhibitory Effect of Antioxidants on Hydroxyl Radical Generation from Methylguanidine: An ESR Study

Methylguanidine (MG) is known as not only a nephrotoxin but also as a neurotoxine. We have previously showed that MG itself generates hydroxyl radicals (•OH) in an in vitro study. In this study, we examined the inhibitory effects of ascorbate, EPC-K₁ (α-tocopheryl-l-ascorbate-2-O-phosphate diester), Trolox (water-soluble vitamin E analogue), and glutathione (GSH) on •OH generation from MG using an electron spin resonance (ESR) spectrometry with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). It was found that these compounds have potent inhibitory effect on •OH generation from MG in the order of ascorbate > GSH > EPC-K₁ > Trolox. Special issue article in honor of Dr. Akitane Mori.