Free Radical Quenchers Research Articles

Oxalate mediated nephronal impairment and its inhibition by c-phycocyanin: A study on urolithic rats

The assumption of oxidative stress as a mechanism in oxalate induced renal damage suggests that antioxidants might play a beneficial role against oxalate toxicity. An in vivo model was used to investigate the effect of C-phycocyanin (from aquatic micro algae; Spirulina spp.), a known antioxidant, against calcium oxalate urolithiasis. Hyperoxaluria was induced in two of the 4 groups of Wistar albino rats (n = 6 in each) by intraperitoneally injecting sodium oxalate (70 mg/kg body weight). A pretreatment of phycocyanin (100 mg/kg body weight) as a single oral dosage was given, one hour prior to oxalate challenge. An untreated control and drug control (phycocyanin alone) were employed. Phycocyanin administration resulted in a significant improvement (p < 0.001) in the thiol content of renal tissue and RBC lysate via increasing glutathione and reducing malondialdehyde levels in the plasma of oxalate induced rats (p < 0.001), indicating phycocyanin's antioxidant effect on oxalate mediated oxidative stress. Administering phycocyanin after oxalate treatment significantly increased catalase and glucose-6-phosphate dehydrogenase activity (p < 0.001) in RBC lysate suggesting phycocyanin as a free radical quencher. Assessing calcium oxalate crystal retention in renal tissue using polarization microscopy and renal ultrastructure by electron microscopy reveals normal features in phycocyanin-- pretreated groups. Thus the study presents positive pharmacological implications of phycocyanin against oxalate mediated nephronal impairment and warrants further work to tap this potential aquatic resource for its medicinal application.

Xanthohumol isolated from Humulus lupulus Inhibits menadione-induced DNA damage through induction of quinone reductase.

The female parts of hops (Humulus lupulus L.) show estrogenic effects as well as cancer chemopreventive potential. We analyzed the chemopreventive mechanism of hops by studying its antioxidative activities and its effect on the detoxification of a potentially toxic quinone (menadione). The detoxification enzyme quinone reductase [(NAD(P)H:quinone oxidoreductase, QR] protects against quinone-induced toxicity and has been used as a marker in cancer chemoprevention studies. Although the hop extract was only a weak quencher of free radicals formed from 1,1-diphenyl-2-picrylhydrazyl, it demonstrated strong QR induction in Hepa 1c1c7 cells. In addition, compounds isolated from hops including xanthohumol (XH) and 8-prenylnaringenin were tested for QR induction. Among these, XH was the most effective at inducing QR with a concentration required to double the specific activity of QR (CD value) of 1.7 +/- 0.7 microM. In addition, pretreatment of Hepa1c1c7 cells with XH significantly inhibited menadione-induced DNA single-strand breaks. The QR inhibitor dicumarol reversed the protective effect of XH against menadione-induced DNA damage. Because the expression of QR and other detoxifying enzymes is known to be upregulated by binding of the transcription factor Nrf2 to the antioxidant response element (ARE), the reporter activity mediated by ARE in HepG2-ARE-C8 cells was investigated after incubation with XH for 24 h. Under these conditions, XH increased ARE reporter activity in a dose-dependent manner. One mechanism by which XH might induce QR could be through interaction with Keap1, which sequesters Nrf2 in the cytoplasm, so that it cannot activate the ARE. Using LC-MS-MS, we demonstrated that XH alkylates human Keap1 protein, most likely on a subset of the 27 cysteines of Keap1. This suggests that XH induces QR by covalently modifying the Keap1 protein. Therefore, XH and hops dietary supplements might function as chemopreventive agents, through induction of detoxification enzymes such as QR.

Nondestructive Determination of Solids and Carotenoids in Tomato Products by Near-Infrared Spectroscopy and Multivariate Calibration

Tomato is an important player in the agricultural market. It is the second most consumed vegetable in the world and is a source of important micronutrients such as lycopene and beta-carotene. Recent research has demonstrated that these carotenoids can act as free-radical quenchers in the body and prevent aging, tissue damage, heart disease, and certain cancers. Besides these microcomponents, tomato is composed of soluble and insoluble solids. In industry, these solids govern factory yield and play a major role in the tomato trade. Nowadays, standard methods for determining tomato solids and carotenoids are time and labor consuming. In this work, we present the development of a simultaneous and nondestructive method for determining total and soluble solids, as well as lycopene and beta-carotene, in tomato products by near-infrared spectroscopy. PLS-1 was the calibration technique chosen. For spectra preprocessing, MSC and second derivative were applied. As variable selection techniques, the correlogram cutoff, the successive projections algorithm, the dimension wise selection, and spectra splitting approach were applied. Best models presented satisfactory prediction abilities evaluated through its RMSEP and r values: total solids 0.4157, 0.9998; soluble solids 0.6333, 0.9996; lycopene 21.5779, 0.9996; beta-carotene 0.7296, 0.9981.

Antioxidant enzyme response studies in H 2O 2-stressed porcine muscle tissue following treatment with oregano phenolic extracts

The effect of oregano ( Origanum vulgare) extracts rich in phenolics in ameliorating the adverse effects of oxidative stress caused by H 2O 2 by mediating an antioxidant enzyme response in porcine muscle tissue was investigated. The changes in the total phenolic content, antioxidant activity, proline content, malondialdehyde (MDA) content, activity of glucose-6-phosphate dehydrogenase (G6PDH), which is the first commited step of pentose phosphate pathway, antioxidant enzymes including total peroxidase (TPX), superoxide dismutase (SOD), and catalase (CAT) activity in stressed porcine muscle tissue was determined. The total phenolic content of control and H 2O 2 treated porcine tissue remained constantly low throughout the study. In the oregano treated tissues the phenolic content increased four-fold immediately indicating that the porcine cells had imbibed the oregano phenolics efficiently. In the case of H 2O 2 + oregano treatment the values were higher than control and H 2O 2 alone but less than oregano alone. This indicates that the oregano phenolics inside the porcine cell were potentially reactive and likely being utilized for counteracting the harmful effects of H 2O 2. In the oregano and H 2O 2 + oregano treated tissues the 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging antioxidant activity almost doubled from 35% to 75% by 8 h. This also further indicates the high free radical scavenging, antioxidant potential of the oregano phytochemicals in reducing the harmful effects of H 2O 2. In the oregano and H 2O 2 + oregano treatments the G6PDH activity increased seven-fold compared to stressed and control tissue, which coincides with stimulated TPX activity. The H 2O 2 stress alone enhanced G6PDH activity slightly and this response occurred concomitantly with an increase in SOD and CAT activity. The oregano phenolics were able to counter the H 2O 2 effects with reduced need for higher SOD expression. In the present research the highest antioxidant enzyme activity was observed in the stressed H 2O 2 treatment at 8 h incubation indicating the active role of CAT in modulating the harmful effects of H 2O 2, which directly correlated to higher SOD activity. In the case of oregano and oregano + H 2O 2, proline levels were higher compared to H 2O 2 alone, again suggesting the ameliorating effect of oregano on oxidative stress and this may involve proline-linked stimulation of pentose phosphate pathway. The MDA content in the case of oregano + H 2O 2 treatment was comparatively lower than H 2O 2 alone showing the protective effects of oregano against reactive oxygen species and eventually from membrane damage. The major implication from this study is evidence that oregano being rich in phenolics is an effective direct quencher of free radicals. Further, the same phenolics play a beneficial role in protecting porcine muscle tissue from the harmful effects of reactive oxygen species through regulation of antioxidant enzyme response through the phenolic-dependent peroxidases with dependency on pentose phosphate pathway but with reduced dependency on SOD and CAT.

Antioxidant Properties of Phosphates and Other Additives During the Storage of Raw Mackerel and Lake Trout

ABSTRACT: The addition of phosphates, such as sodium tripolyphosphate (STPP), to mackerel samples showed an antioxidant effect, although not as strong as that of propyl gallate (PG), ascorbic acid (AA), or erythorbic acid (EA). Phosphates were particularly effective in the white muscle. This effect was not observed in lake trout, where EA was a strong pro‐oxidant. In mackerel, the addition of STPP with other free radical quenchers did not enhance the anti‐oxidant effect. Smaller, monovalent cation phosphates were better antioxidants than larger cations with higher valences. Although the concentration and type of phosphate may affect the oxidation rate of the mackerel, their effect was found to be masked by certain factors.

Metabolic aspects of endotoxin as a model of septic shock--approached from oxidative stress

Despite the remarkable progress in intensive care medicine, sepsis and shock continue to be major clinical problems in intensive care units. Septic shock may be associated with a toxic state initiated by the stimulation of monocytes by bacterial toxins such as endotoxin, which is released into the bloodstream. This study describes the role of oxidative stress in endotoxin-induced metabolic disorders. We demonstrate that endotoxin injection results in lipid peroxide formation and membrane injury in experimental animals, causing decreased levels of free radical scavengers or quenchers. Interestingly, it was also suggested that tumor necrosis factor (TNF)-induced oxidative stress occurs as a result of bacterial or endotoxin translocation under conditions of reduced reticuloendothelial system function in various disease states. In addition, we suggest that intracellular Ca2+, Zn2+, or selenium levels may participate, at least in part, in the oxidative stress during endotoxemia. On the other hand, it is also suggested that the extent of endotoxin-induced nitric oxide (NO) formation may be due, at least in part, to a change in heme metabolic regulation during endotoxemia. However, in our experimental model, NO is not crucial for lipid peroxide formation during endotoxemia. Sho-saiko-to is one of the most frequently prescribed Kampo medicines and has primarily been used to treat chronic hepatitis. We report that Sho-saiko-to decreases the rh TNF-induced lethality in galactosamine-hypersensitized mice and protects mice against oxygen toxicity and Ca2+ overload in the cytoplasm or mitochondria during endotoxemia. We further suggest that Sho-saiko-to shows a suppressive effect on NO generation in macrophages stimulated with endotoxin and that it may be useful in improving endotoxin shock symptoms.

Changes in carotenoid composition in different developmental stages of copepods: Pseudocalanus acuspes Giesbrecht and Acartia spp.

Carotenoid contents and composition were studied in three successive developmental groups of copepod populations from the southern Baltic Sea. Samples were collected with >80% prevalence of any one of three developmental groups: (i) nauplii, (ii) copepodids I-III and (iii) copepodids IV-V and also adults of Pseudocalanus acuspes Giesbrecht and Acartia spp. (Copepoda: Calanoida). Samples were collected over the years 1991-1999 from May to September at six sampling sites in the southern Baltic Sea. The carotenoids were analysed by means of reverse-phase high-performance liquid chromatography (RP-HPLC). The mean total carotenoid concentrations (astaxanthin, astaxanthin esters, canthaxanthin and other carotenoid unidentified and derived from the diet) found in three groups of developmental stages for P. acuspes were 556 μg g -1 dry weight (d.w.) in naupliar stages, 791 μg g -1 in copepodids I-III, and 868 μg g -1 in copepodids IV-V and adults. The average carotenoid concentrations in Acartia spp. were 619, 764 and 872 μg g -1 d.w., respectively. Significant changes were observed in the proportion of carotenoids of separate developmental groups. Astaxanthin and canthaxanthin occurred in all developmental groups, with the evident dominance of astaxanthin. However, copepodid groups I-III and especially IV-V including adults, showed an increased proportion of astaxanthin esters. This suggests that astaxanthin is the main active carotenoid in copepod metabolism. It acts most probably as an efficient free radical quencher and may be involved in rapid metabolism of stored lipids in mostly unfeeding young nauplii. The feeding stages (late nauplii and copepodids I-III and IV-V) are evidently able to metabolize this pigment by esterfication and further degradation.

Dietary Dunaliella bardawil, a beta-carotene-rich alga, protects against acetic acid-induced small bowel inflammation in rats.

Reactive oxygen species mediate tissue injury in inflammatory bowel disease. Beta-carotene is known as a potent free radical quencher and antioxidant. The authors evaluated the efficacy of prefeeding Dunaliella bardawil, rich in beta-carotene, to ameliorate acid-induced enteritis in a rat model. Enteritis was induced in female Sprague-Dawley rats by injection of 2 mL acetic acid (0.67 mol/L) to a ligated duodenal loop following 10 weeks of feeding diets containing beta-carotene and compared with various controls. The effects of beta-carotene were evaluated by changes in myeloperoxidase activity, histology, and histomorphometry. Feeding beta-carotene resulted in suppressed mucosal myeloperoxidase activity, both basal and that induced by acetic acid injection. Acetic acid treatment induced major histopathologic changes in the duodenal mucosa, including small, irregular, and distorted villi; damage to the epithelium; edema of the lamina propria; accumulation of inflammatory cells; and hemorrhage. Beta-carotene treatment prevented these acid-induced histopathologic changes, and this was confirmed by histomorphometry of the villi. These results demonstrate the effectiveness of beta-carotene in a rat model as a prophylactic dietary measure in reducing the effects of acid-induced enteritis and raise the possibility that patients with Crohn's disease may benefit from the consumption of natural beta-carotene.

Mechanism of DNA strand breakage induced by photosensitized tetracycline–Cu(II) complex

Tetracyclines (TCs) in combination with Cu(II) ions exhibited significant DNA damaging potential vis a vis tetracyclines per se. Interaction of tetracyclines with DNA resulted in alkylation at N-7 and N-3 positions of adenine and guanine bases, and caused destabilization of DNA secondary structure. Significant release of acid-soluble nucleotides from tetracycline-modified DNA upon incubation with S 1 nuclease ascertained the formation of single stranded regions in the DNA. Also, the treatment of tetracycline-modified DNA with 0.1 and 0.5 M NaOH resulted in 62 and 76% hydrolysis compared to untreated control. Comparative alkaline hydrolysis of DNA modified with tetracycline derivatives showed differential DNA damaging ability in the order as DOTC>DMTC>TC>OTC>CTC. Addition of Cu(II) invariably augmented the extent of tetracycline-induced DNA damage. The alkaline unwinding assay clearly demonstrated the formation of approximately six strand breaks per unit DNA at 1:10 DNA nucleotide/TC molar ratio in the presence of 0.1 mM Cu(II) ions. At a similar Cu(II) concentration, a progressive transformation of covalently closed circular (CCC) (form-I) plasmid pBR322 DNA to forms-II and -III was noticed with increasing tetracycline concentrations. The results obtained with the free-radical quenchers viz. mannitol, thiourea, sodium benzoate and superoxide dismutase (SOD) suggested the involvement of reactive oxygen species in the DNA strand breakage. It is concluded that the tetracycline–Cu(II)-induced DNA damage occurs due to (i) significant binding of tetracycline and Cu(II) with DNA, (ii) methyl group transfer from tetracycline to the putative sites on nitrogenous bases, and (iii) metal ion catalyzed free-radical generation in close vicinity of DNA backbone upon tetracycline photosensitization. Albeit, the DNA alkylation and strand cleavage are repairable lesions, but any defect in the critical repair pathway may augment the damage accumulation and mutagenesis.

Photosensitized paraquat-induced structural alterations and free radical mediated fragmentation of serum albumin

Photosensitization of paraquat with photosynthetically active radiations (PAR) induced substantial production of both the hydroxyl radicals ( ⋅OH) and superoxide anions (O 2 ⋅−) under in vitro conditions. Addition of transition metal ion, Cu (II) enhanced the paraquat-induced ⋅OH radical production by 1.8-fold. Treatment of bovine serum albumin (BSA) with photosensitized paraquat resulted in a dose dependent fragmentation of protein. The quantitative analysis revealed the release of 73 μM acid soluble amino groups and 450 μM carbonyl groups from treated albumin at the highest albumin–paraquat molar ratio of 1:8 in presence of 200 μM Cu (II). The results with the free radical quenchers such as mannitol and superoxide dismutase (SOD) clearly reflected the involvement of ⋅OH radicals in protein fragmentation process. The fluorescence data revealed significantly higher binding of paraquat with serum albumin. The binding constants ( K a) and binding capacity ( n) of albumin for paraquat were determined to be 3.4×10 5 l/mole and 12.9, respectively. Fluorescence emission spectra exhibited significant quenching of the intrinsic fluorescence of albumin upon addition of paraquat at increasing molar ratios. This is attributed to induced conformational changes in protein structure upon paraquat interaction at specific sites on albumin molecule. Most likely, the alkyl group transfers occur from N1 and/or N1′ positions of paraquat to the electron rich sites at critical amino acid residues on treated protein. At higher paraquat concentrations, the albumin–paraquat interaction resulted in adduct formation with concurrent protein alkylation and free radical mediated fragmentation. Thus, on the basis of these results, the paraquat–protein interaction leading to alkylation, structural alterations and/or fragmentation of biological macromolecules has been suggested as an important factor for agrochemical-induced toxicity.

New concepts in organ preservation

Organ preservation between donor and recipient is an important link in a chain that ultimately should lead to long term survival of the recipient thanks to a well-preserved, functionally intact organ. The period of organ ischaemia outside the body is subject to a number of biochemical stress factors which become known in more detail as knowledge on biochemical and immunological mechanisms improves. Efficacy of preservation fluids hence reduction of ischaemia injury may become enhanced by such additives as ion channel blockers, enzyme inhibitors, haeme oxygenase modulators, endothelin-1-inhibitors, quenchers of free radicals and anti-apoptotic agents. Many of these compounds, albeit of great theoretical interest, have not (yet?) made their way into clinical practice. This contribution is a survey of some promising agents, concentration and physicochemical interactions of which are analysed in some detail.

Tetracycline–Cu(II) photo-induced fragmentation of serum albumin

The protein-damaging potential of photosensitized tetracycline hydrochloride alone and in combination with the metal ion Cu(II) was assessed using serum albumin as a model protein. Exposure of tetracycline to white light in an aqueous solution triggered the generation of significant amounts of reactive oxygen species (ROS) and engendered substantial protein damage. The appearance of distinct low-molecular-mass protein bands on 10% SDS-polyacrylamide gel ascertained the tetracycline concentration-dependent fragmentation of albumin. Photoexcited tetracycline in combination with 100 μM Cu(II) enhanced the protein fragmentation process with concurrent increase in free radical production. The significant release of acid-soluble amino groups and carbonyl groups from treated albumin provided quantitative estimation of protein fragmentation at 0–1.0 mM concentrations of tetracycline. Cu(II) ions per se did not cause any perceptible protein damage. The results with free radical quenchers suggested the role of hydroxyl radicals ( OH) in tetracycline–Cu(II)-induced protein fragmentation, as no superoxide dismutase (SOD)-mediated quenching effect was noted. The generation of free radicals upon tetracycline photoexcitation and consequent protein fragmentation may be considered as important factors in augmentation of tetracycline-induced phototoxic responses.

UVA-340 as energy source, mimicking natural sunlight, activates the transcription factor AP-1 in cultured fibroblasts: evidence for involvement of protein kinase-C.

Ultraviolet radiation (UVR) is known to affect a variety of cellular functions, including gene expression. A number of signaling pathways have been suggested to mediate these effects, including the participation of activator protein-1 (AP-1), activator protein-2 (AP-2) and nuclear factor-kappa B (NF-kappa B). The divergent results from previous studies could be explained, at least in part, by the source of UVR with different spectral characteristics as well as the type of cells employed as targets. In this study we have utilized UVA-340 as an energy source with output which closely matches the spectrum of natural sunlight over the range of 295-350 nm for irradiation of cultured fibroblasts. Combination of electrophoretic mobility shift assays and Northern analyses revealed activation of AP-1 but not NF-kappa B or AP-2. Inhibition studies further suggested the participation of protein kinase-C, but not protein kinase-A, and that an inhibitor of mitogen-activated protein kinase (MEK-1/2) did not alter the AP-1 activation. Free radical quenchers, sodium azide and N-acetylcysteine, did not affect the AP-1 binding activity. Finally, UVA-340 was shown to enhance transcriptional expression of the type-VII collagen gene (COL7A1), which is endogenously expressed in dermal fibroblast in an AP-1 dependent manner. Introduction of a mutation into the AP-1 site of the COL7A1 promoter abolished this activation. Thus, our results obtained by utilizing a novel energy source, UVA-340, mimicking natural sunlight at UVB and lower UVA range indicate a role for AP-1 in mediating the enhanced gene expression by UVR. Collectively, these results suggest that AP-1 is an important mediator of UVR action in fibroblasts.

Cellular photodestruction induced by hypericin in AY-27 rat bladder carcinoma cells.

In a recent clinical study we showed that hypericin accumulates selectively in urothelial lesions following intravesical administration of the compound to patients. In the present study the efficacy of hypericin as a photochemotherapeutic tool against urinary bladder carcinoma was investigated using the AY-27 cells (chemically induced rat bladder carcinoma cells). The uptake of hypericin by the cells increased by prolonging the incubation time and increasing the extracellular hypericin concentration. Photodynamic treatment of the cells incubated with 0.8 and 1.6 microM hypericin concentrations resulted in remarkable cytotoxic effects the extent of which depended on the fluence rates. Photoactivation of 1.6 microM hypericin by 0.5, 1.0 or 2.0 mW/cm2 for 15 min resulted in 3, 30 and 95% of the antiproliferative effect, respectively. Increasing the photoactivating light dose from 0.45 to 3.6 J/cm2 resulted in a five-fold increase in hypericin photodynamic activity. Irrespective of the fluence rates and irradiation times incubation of the cells with 10 microM hypericin induced rapid and extensive cell death in all conditions. The type of cell death (apoptosis or necrosis) induced by photoactivated hypericin depended largely on the hypericin concentration and the postirradiation time. At lower hypericin concentrations and shorter postirradiation times apoptosis was the prominent mode of cell death; increasing the hypericin concentration and/or prolonging the postirradiation time resulted in increased necrotic cell death. Cell pretreatment with the singlet oxygen quencher histidine, but not with the free-radical quenchers, significantly protected the cells from photoactivated hypericin-induced apoptosis, at least when a relatively low concentration (1.25 microM) was used. This result suggests the involvement of a Type-II photosensitization process. However, cells treated with higher hypericin concentrations (2.5-5 microM) were inadequately protected by histidine. Since hypericin is thus shown to be a potent and efficient photosensitizer, and since the conditions used were the same as when hypericin is used clinically to locate early-stage urothelial carcinoma lesions, hypericin may well become very important for the photodynamic treatment of superficial bladder carcinoma.

Ozone treatment rapidly activates MAP kinase signalling in plants.

Brief exposure to ozone, a potent cross-inducer of plant stress responses, leads within minutes to activation of an ERK-type MAP kinase (approximately 46 kDa) in tobacco. This activation process is calcium-dependent and can be blocked both by free radical quenchers and by a specific inhibitor of MEK-1 (MAPKK). Hydrogen peroxide and superoxide anion radicals can substitute for ozone as the activation stimulus, which does not appear to require salicylate as an intermediary. The properties of the ozone-induced MAPK suggest that it may be SIPK (salicylate-induced protein kinase), a tobacco MAPK that is activated by a variety of stress treatments. The ability of ozone to activate SIPK indicates that this protein kinase acts as a very early transducer of redox stress signals in plant cells.

Oxidation of Bilirubin in the Brain—Further Characterization of a Potentially Protective Mechanism

Bilirubin is a well-known neurotoxin and presents a particular problem in newborn infants. This is partly due to the high incidence of unconjugated hyperbilirubinemia in that age group, but may also be due to increased vulnerability to bilirubin toxicity. The brain may be able to protect itself against bilirubin toxicity through a process of oxidation. The responsible enzyme is localized on the inner mitochondrial membrane and appears to be more active in glia than in neurons and to increase in activity with postnatal maturation. Here we have investigated the possibility that the responsible enzyme might be a cytochrome oxidase, malate dehydrogenase, or monoamine oxidase, all enzymes located on the inner mitochondrial membrane. Mitochondria were obtained from rat brains through homogenization and differential centrifugation in sucrose medium. The ability of mitochondrial membranes to oxidize bilirubin was measured by following the change in optical density at 440 nm of a bilirubin solution to which a membrane suspension had been added. The activity was not changed by in vitro inhibitors of malate dehydrogenase or monoamine oxidase, but was moderately inhibited by ketoconazole and clotrimazole, both known inhibitors of hepatic cytochrome P450 oxidases. Activity was inhibited by depletion of cytochrome c in the mitochondria and reconstituted by reintroducing cytochrome c into the reaction mixture. The reaction was not modified by the addition of a free radical quencher, but was inhibited by removal of oxygen from the reaction mixture. The activity was significantly inhibited by cyanide. Activity was retained in a 100,000-g pellet and was not influenced by the addition of NAD, NADP, NADH, NADPH, GSH, or GSSH to this pellet. We conclude that the bilirubin-oxidizing activity in brain mitochondrial membranes is cytochrome c dependent, but does not appear to be unequivocally identifiable as a cytochrome P450 oxidase.

ROLE OF FREE RADICAL QUENCHERS IN THE CHARGE TRANSFER POLYMERIZATION OF STYRENE AND ALKYLMETHACRYLATES

Charge transfer polymerization of styrene and alkylmethacrylates, involving an electron donor and acceptor molecules, is accelerated by employing free radical quenchers such as hydroquinone, monomethylether of hydroquinone and galvinoxyl result-ing in higher polymer yields. The best results are achieved when hydroquinone is employed as a free radical quencher. The addition of free radical quenchers in the system also decreased the molecular weights of polymers. The higher polymer yields and lower molecular weights are due to the predominant participation of ionic mechanism operative in the system.

Inhibition of Biochemical Model Reactions for Inflammatory Processes by Plant Extracts: A Review on Recent Developments

All processes of oxygen activation include very reactive intermediates. Therefore, aerobic cells must cope with- and to some extent also adapt to- oxidative stress provoked for example by infections or intoxications, where these reactive intermediates accumulate. Dependent on the strength of these impact, several symptoms indicate the deviation from normal, steady-state-metabolism. Intrinsic radical scavenging processes or compounds administered with food thus have to warrant metabolic control within certain limits. Antioxidants which in many cases are free radical scavengers or quenchers of activated states comprise a wealth of classes of organic molecules including phenolics, probably as the most prominent ones. In this communication mechanisms of protection from oxidative damage are discussed. Furthermore, examples of antioxidative functions of a few important natural products in certain diseases are reported.

Superoxide as an Intermediate Signal for Serotonin-Induced Mitogenesis

Serotonin (5-HT) stimulates tyrosine phosphorylation and proliferation of bovine pulmonary artery smooth muscle cells (SMC) through its active transport (Lee et al, 1991). The present studies show that 5-HT also rapidly elevates O 2 ·− formation by these cells within 10 minutes as measured by a lucigenin-enhanced chemiluminescence assay. The O 2 ·− free radical quencher, Tiron, and N-acetyl-cysteine, a substrate for glutathione, block both the 5-HT-induced formation of O 2 ·− and cellular proliferation. Similarly, inhibition of 5-HT transport with imipramine or treatment of cells with diphenyliodonium, a NAD(P)H oxidase inhibitor, block both 5-HT-induced elevation of O 2 ·− and cellular proliferation. Alpha-hydroxyfarnesylphosphonic acid, an inhibitor of p21 ras, also blocks 5-HT-induced proliferation. Endothelial cells from the same vessel show neither 5-HT-induced proliferation nor stimulation of O 2 ·− formation. We conclude that 5-HT induced cellular proliferation of SMC through signaling pathways that utilize its transport system and O 2 ·− formation.

New long-wavelength perylenequinones. The reaction between hypocrellin B and mercapto compounds

Certain new mercapto-substituted hypocrellin B (HB) derivatives have been synthesized and characterized. The possible mechanism for this reaction, and the properties of the resulting compound, are discussed. Interaction of HB with mercapto compounds in dimethyl sulfoxide containing ammonium hydroxide proceeded very quickly, and the mono- or di-substituted HB derivatives were formed. Their significantly enhanced red absorptivities and strong 1O 2-generating functions may qualify them as promising PDT agents. In addition, the semiquinone radical anion of HB (HB −.) was one of the reaction intermediates detected by ESR and Uv-vis spectrum. Moreover, the effect of free radical quenchers on this reaction have also been investigated. On the basis of the experimental evidence, the mechanism of free radical addition and nucleophilic addition are proposed.