Modification of primary and secondary metabolism of potato plants by nitrogen application differentially affects resistance to Phytophthora infestans and Alternaria solani.

Potato plants ( SOLANUM TUBEROSUM L. cv. Indira) were grown at two levels of N supply in the greenhouse. Plants supplied with 0.8 g N per plant (high N variant) showed significantly increased biomass as compared to plants without additional N fertilisation (low N variant). C/N ratio was lower and protein content was higher in leaves of the high N variant. The concentration of chlorogenic acids and flavonols was significantly lower in leaves from the high N variant. Whereas resistance to ALTERNARIA SOLANI increased when plants were supplied with additional nitrogen, these plants were more susceptible to PHYTOPHTHORA INFESTANS. After infection with both pathogens, we found a strong induction of p-coumaroylnoradrenaline and p-coumaroyloctopamine, which are identified for the first time in potato leaves and are discussed as resistance factors of other solanaceous plants.

Radical scavenging and anti-inflammatory properties of STW 5 (Iberogast) and its components.

A combination of ethanolic extracts from nine medicinal plants is successfully used in STW 5 (Iberogast((R))) for treatment of gastrointestinal disorders. To elucidate possible modes of action, the focus of this study is on antioxidant properties of the phytomedicine STW 5. In fact, functional gastrointestinal diseases, such as non-ulcer dyspepsia (NUD) and irritable bowel syndrome, are often initiated by or correlated to inflammatory processes, where oxidants such as reactive oxygen species (ROS) play a crucial role. Prominent in vivo sources of ROS generation are represented by the enzymes xanthine oxidase (XOD) or myeloperoxidase (MPO). Applying these enzymes in models in vitro, we show that STW 5 and its components possess strong antioxidant activities. Depending on the model investigated, even pro-oxidant activities of single components of STW 5 could be observed. Interestingly, these effects were absent in STW 5, indicating cooperation between the components. Moreover, if one of the component extracts of STW 5 is omitted, the antioxidant activity is reduced. Thus we conclude that all the single extracts combined in STW 5 are of importance for the therapeutic effect, working in concert. The component of STW 5 performing best in vitro differed with the model investigated, respectively, with ROS and ROS generators. In the XOD system, the extracts of lemon balm leaf and peppermint leaf showed the best antioxidant result, whereas concerning MPO driven chlorination reactions, bitter candy tuft extract was the most efficient antioxidant. Best protection against peroxynitrite induced oxidation of methionine like sulfur-compounds exhibited the STW 5 components lemon balm leaf, Matricaria flower and peppermint leaf.

The monoterpene terpinolene from the oil of Pinus mugo L. in concert with alpha-tocopherol and beta-carotene effectively prevents oxidation of LDL.

Antioxidants from several nutrients, e.g. vitamin E, beta-carotene, or flavonoids, inhibit the oxidative modification of low-density lipoproteins. This protective effect could possibly retard atherogenesis and in consequence avoid coronary heart diseases. Some studies have shown a positive effect of those antioxidants on cardiovascular disease. Another class of naturally occurring antioxidants are terpenoids, which are found in essential oils. The essential oil of Pinus mugo and the contained monoterpene terpinolene effectively prevent low-density lipoprotein (LDL)-oxidation. In order to test the mechanism by which terpinolene protects LDL from oxidation, LDL from human blood plasma enriched in terpinolene was isolated. In this preparation not only the lipid part of LDL is protected against copper-induced oxidation--as proven by following the formation of conjugated dienes, but also the oxidation of the protein part is inhibited, since loss of tryptophan fluorescence is strongly delayed. This inhibition is due to a retarded oxidation of intrinsic carotenoids of LDL, and not, as in the case of some flavonoids, attributable to a protection of intrinsic alpha-tocopherol. These results are in agreement with our previous results, which showed the same effects for a monoterpene from lemon oil, i.e. gamma-terpinene.

Growth parameters and resistance against Drechslera teres of spring barley (Hordeum vulgare L. cv. Scarlett) grown at elevated ozone and carbon dioxide concentrations.

Spring barley ( Hordeum vulgare L. cv. Scarlett) was grown at two CO2 levels (400 vs. 700 ppm) combined with two ozone regimes (ambient vs. double ambient) in climate chambers for four weeks, beginning at seedling emergence. Elevated CO2 concentration significantly increased aboveground biomass, root biomass, and tiller number, whereas double ambient ozone significantly decreased these parameters. These ozone-induced reductions in growth parameters were strongly overridden by 700 ppm CO2. The elevated CO2 level increased C : N ratio of the leaf tissue and leaf starch content but decreased leaf protein levels. Exposure to double ambient ozone did not affect protein content and C : N ratio but dramatically increased leaf starch levels at 700 ppm CO2. Resistance against Drechslera teres (Sacc.) Shoemaker was increased in leaves grown at double ambient ozone but was less obvious at 700 ppm than at 400 ppm CO2. Constitutive activities of beta-1,3-glucanase and chitinase were significantly higher in leaves grown at double ambient ozone compared to ambient ozone levels. The sum of methanol-soluble and alkali-released cell wall-bound aromatic metabolites (i.e., C-glycosylflavones and several structurally unidentified metabolites) and lignin contents did not show any treatment-dependent differences.

Vitamin C, vitamin E and flavonoids.

All inflammatory processes include oxygen-activating processes where reactive oxygen species are produced. Intrinsic radical scavenging systems or compounds administered with food warrant metabolic control within certain limits. Antioxidants, which in many cases are free radical scavengers or quenchers of activated states, comprise a vast number of classes of organic molecules including most prominently the phenolics. In this report, mechanisms of protection from oxidative damage by the antioxidants vitamin C and E and flavonoids, as present in most plant extracts used as natural drugs, are summarized. For this purpose the principle of oxygen activation during representative disease processes and the protective actions of antioxidants are outlined in short.

Synergistic inhibition of low-density lipoprotein oxidation by rutin, gamma-terpinene, and ascorbic acid.

Low-density lipoprotein (LDL) oxidation may play a significant role in atherogenesis. Flavonoids are well-known for their excellent antioxidative capacity in various model systems, therefore we examined the behaviour of rutin, a quercetin-3-rutinosid, in the copper-mediated LDL oxidation. Rutin alone has been shown to protect LDL against oxidation. Furthermore we investigated the combination of rutin with a hydrophilic (ascorbate) and a lipophilic antioxidant (gamma-terpinene) in copper-mediated LDL oxidation. In both cases we found a synergistic effect on lag phase prolongation. To elucidate whether this effect mainly depends on the copper chelating ability of rutin we examined its reaction in more detail. Although inhibiting the oxidation of alpha-linolenic acid in the "rose bengal system" no direct influence of a copper-rutin-complex was determined. We conclude that a redox active copper-rutin-complex is still able to initiate the LDL oxidation but may prevent copper from a reaction at the binding sites of apoB-100. The synergistic effect in preventing LDL oxidation is due to this trapping of copper in a complex in the case of ascorbate. The synergistic action of rutin and gamma-terpinene can be explained by different distribution of rutin and gamma-terpinene in, and around the LDL-particle, respectively.

PPARgamma ligands and ATRA inhibit the invasion of human breast cancer cells in vitro.

Invasion and metastasis are the main causes of death in breast cancer patients. Increased expression of matrix metalloproteinases (MMPs), especially gelatinases (MMP-2 and -9), has been closely associated with tumor progression. One of the nuclear hormone receptors (NHR), peroxisome proliferator-activated receptor gamma (PPARgamma), is a ligand-activated transcriptional factor that regulates cell proliferation, differentiation and apoptosis in both normal and cancer cells. Recent data indicate that PPARgamma activation by its ligands can also lead to the inhibition of gelatinase B (MMP-9) and the blockage of migration in macrophages and muscle cells, implying the possibility that PPARgamma ligands may possess anti-invasive activities on tumor cells. In this study, we showed that treatment of the highly aggressive human breast cancer cell line MDA-MB-231 with the synthetic PPARgamma ligands pioglitazone (PGZ), rosiglitazone (RGZ), GW7845 or its natural ligand 15-deoxy-delta 12, 14-prostaglandin J2(15d-PGJ2), at concentrations at which no obvious cytotoxicity was observed in vitro, led to a significant inhibition of the invasive capacities of this cell line through a reconstituted basement membrane (Matrigel) in a Transwell chamber model. All-trans-retinoic acid (ATRA), a ligand for retinoic acid receptor (RAR), was also studied and showed a similar inhibitory effect on invasion. Although no change was observed in the expression of MMP-9 after challenge with PPARgamma ligands and/or ATRA on this cell line, the natural tissue inhibitor of gelatinases, namely the tissue inhibitor of MMP 1 (TIMP-1) was upregulated by these treatments and the gelatinolytic activities of gelatinases in the conditioned media were decreased. Since MMP-2 was not detectable in the conditioned media of MDA-MB-231 cells, and the gelatinolytic activities of the conditioned media were reduced only by MMP-9 neutralizing antibodies, it is most likely that the reduction of gelatinolytic activities by PPARgamma ligands and/or ATRA was due to the decrease of MMP-9 activities. Because MMP-9 was absolutely required in the transmigration of this cell line through Matrigel in our in vitro model as demonstrated by neutralizing antibodies against MMP-2 and -9, we concluded that down-regulation of gelatinase activities is, at least in part, responsible for the reduction of the invasive capacities of MDA-MB-231 cell line in vitro. Our results, for the first time, indicate that PPARgamma ligands may have therapeutic value for the treatment of highly invasive breast cancer by targeting its invasive behavior.

Novel therapeutic approach: ligands for PPARgamma and retinoid receptors induce apoptosis in bcl-2-positive human breast cancer cells.

Effective treatment of tumors is often associated with activation of the endogenous apoptosis pathways. We have studied eight breast cancer cell lines (MCF-7, BT20, BT474, MDA-MB-231, MDA-MB-436, SKBR3, T-47D, ZR-75-1) possessing a variety of genetic defects. The clonogenic growth of breast cancer cell lines was inhibited by a ligand for PPARgamma (troglitazone, TGZ) combined with a ligand for either retinoid X receptor (RXR) (LG10069) (4/8 cell lines), RAR (ATRA) (5/8 cell lines) or RAR/RXR and RXR/RXR (9-cis-RA) (5/8 cell lines) independent of their expression of bcl-2, bag-1, ERalpha, and p53. The cell lines (MCF-7, T-47D, ZR-75-1), which expressed both BRCA1 and p27, were extremely sensitive to the inhibitory effect of the combination of TGZ and either ATRA or 9-cis-RA (ED90, 2-5 x 10(-11) M). However, only MCF-7, MDA-MB-231, and ZR-75-1 cells, which expressed a high level of bcl-2 protein, underwent apoptosis when exposed to the combination of TGZ and either ATRA or 9-cis-RA. Importantly, this effect was independent of expression levels of p53, ERalpha, HER-2/neu, bag-1, and BRCA1. Therefore, the combination of ligands for PPARgamma and retinoid receptors may have a therapeutic role for breast cancer.

Antioxidative effects of lemon oil and its components on copper induced oxidation of low density lipoprotein.

Oxidation of low density lipoprotein (LDL) has been implicated in atherogenesis since several years. Therefore many researchers are looking for potent antioxidants which are able to inhibit LDL-oxidation and thus lower the risk for atherosclerosis. In particular several flavonoids have been investigated for their antioxidant capacity and it was shown that many factors influence the ability of flavonoids to retard LDL-oxidation, among others their lipophilic character. Since essential oils and some of their components which are highly lipophilic, have been shown to possess antioxidant properties, their effects on copper-induced LDL-oxidation were analysed. Plasma was incubated with different terpenoid substances and subsequently the LDL was isolated. It could be demonstrated that the terpenoids were enriched in LDL after incubation with plasma. To follow the kinetics of copper induced LDL-oxidation formation of conjugated dienes as well as loss of tryptophan fluorescence were measured. Furthermore the antioxidants alpha-tocopherol, beta-carotene and lycopene were quantified in LDL. It could be shown that particularly lemon oil and one of its components, gamma-terpinene, are efficiently slowing down the oxidation of LDL. This effect is independent of alpha-tocopherol stability in LDL, whereas the loss of carotenoids during oxidation is strongly retarded.

Biological durability and oxidative potential of man-made vitreous fibres as compared to crocidolite asbestos fibres.

In this study we investigated relationships between redox properties and biodurability of crocidolite asbestos fibres and three different man-made vitreous fibres (MMVF): traditional stone wool fibres (MMVF 21), glass fibres (MMVF 11) and refractory ceramic fibres (RCF). Each fibre type was incubated up to 22 weeks in four different incubation media: gamble solution (GS) pH 5.0 and pH 7.4, representing blood plasma without proteins, and surfactant-like solution (SLS) pH 5.0 and pH 7.4. During incubation time aliquots of incubation mixtures were removed and analysed in a biochemical model reaction, mimicking activated phagocytes. In addition, changes of fibre morphology and chemical composition were examined using SEM- and EDX-technology. In the presence of crocidolite asbestos fibres and MMVF 21 the formation of OH*-radicals according to the Haber-Weiss sequence could be demonstrated, whereas MMVF 11 and RCF showed no reactivity. Crocidolite asbestos fibres exhibited a significant higher activity compared with the stone wool fibres at the onset of incubation. The oxidative capacities of these fibre types were shown to depend on both specific surface area and iron content. The oxidative potentials of crocidolite asbestos fibres as well as MMVF 21 were not constant during incubation over several weeks in each incubation medium. The reactivities showed sinoidal curves including reactivities much higher than those at the onset of incubation time. These irregular changes of oxidative capacity may be explained by changes of the redox state of fibre surface-complexed iron. Furthermore our results showed clear differences between incubation of fibres in GS and SLS, respectively, indicating that phospholipids play an important part in fibre dissolution behaviour and oxidative reactivity. In conclusion we suggest, that biodurability testing procedures should not exclusively concentrate on dissolution rates of fibres. They should include fibre characteristics concerning known pathogenic mechanisms to evaluate the real toxic potential of the fibre type looking at. Secondly we suggest, that phospholipids should be constituents of incubation liquids used for standardised fibre biodurability test procedures thus representing more realistic incubation conditions.

Chlorite-hemoprotein interaction as key role for the pharmacological activity of the chlorite-based drug WF10.

WF10 is a chlorite-based drug that modulates macrophages functional states and can be safely administered to humans. WF10 potentially modulates disease-related up-regulation of immune responses both in vitro and in vivo. Thus immune response is influenced in a way that inappropriate inflammatory reactions are downregulated. The molecular mechanisms involved are not completely understood. Biochemical data suggest the reaction of chlorite with hemoproteins as the central step in the activation process of the drug. Thereby a chlorinating agent is generated, resulting in the oxidation of reduced sulfur-containing molecules and in the conversion of amino residues into more or less stable chloramines. The most prominent chloramine in vivo is taurine chloramine. Taurine chloramine is a long-lived molecule with immunomodulatory properties. For instance, taurine chloramine inhibits the generation of macrophage inflammatory mediators such as nitric oxide, prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). This study on the biochemical mechanism of WF10 gives evidence that hemoprotein dependent chlorination of taurine is not only observed in vitro but also very likely in vivo. To characterize the oxidant, generated during heme activation, different methods were used: Chemiluminescence, EPR-spectroscopy, UV/VIS-spectroscopy, gas (GC) and size exclusion chromatography. In summary, the results indicate as the first products of hemoprotein catalyzed chlorite activation a chloroxygen-species (probably HOCl/OCl-) and a ferryl-oxygen species at the hemoprotein active site in analogy to the known peroxidase (compound I and II) intermediates. Moreover, hydrogen peroxide and chlorite seem to react in a similar way with heme centers. It is proposed that WF10 represents an "inactive" transport form of potentially active chlorine. Reactivity of the latter is restricted unless heme moieties in proteins or enzymes activate the "transport form" to perform reactions in analogy to peroxidases (i.e. myeloperoxidase-catalyzed formation of HOCl/OCl-).

Properties of tomato powders as additives for food fortification and stabilization.

The antioxidant activities of two freeze-dried tomato powders as additives for food fortification and stabilization were studied. The two tomato powders were obtained from the whole fruit and from the pulp after "serum" separation, respectively. The antioxidant activity was studied by measuring (a) the inhibition of the singlet oxygen-catalyzed oxidation of alpha-linolenic acid, in the presence or absence of copper ions, as a model of the oxidative processes occurring in foods, and (b) the inhibition of xanthine oxidase (XOD)- and myeloperoxidase (MPO)-catalyzed reactions and copper-induced lipid peroxidation. The partial separation of "serum" decreased the freeze-drying time by 50%. The partially fractionated tomato powder had a 60% lower phenolic content and an 11-fold higher lycopene content than the whole tomato powder, on a dry weight basis. Ascorbic acid was almost completely removed by fractionation. Both the powder obtained from the whole tomato and that obtained from the partially fractionated tomato had antioxidant activity in all the model systems used. Based on these results, we conclude that tomato powders have multifunctional properties, which could address the prevention of oxidative degradations both in foods and in vivo. Therefore, tomato can be regarded as source of food additives for fortification and stabilization, even if it is submitted to technological processes that can cause the loss of the more labile hydrophilic antioxidants.

Vitamin D(3) and its synthetic analogs inhibit the spontaneous in vitro immunoglobulin production by SLE-derived PBMC.

The production of high-affinity pathogenic autoantibodies in systemic lupus erythematosus (SLE) may result from aberrant immune regulation. Since 1,25 dihydroxy vitamin D(3) (1,25 D(3)) has immunoregulatory activity, we examined effects of 1,25 D(3) and its analogs HM, V, MC1288, and KH1060 on autoantibody production and proliferation of SLE PBMC. We found, in SLE, a higher percentage of T, B, and NK expressing vitamin D(3) receptors (VDRs) (P = 0.034, 0.006, 0.012, respectively). Incubating SLE PBMC with 1,25 D(3) compounds significantly reduced proliferation, polyclonal and anti-dsDNA IgG production, and the percentages of CD3(+)/DR(+) T and B (CD19(+)) cells, while elevating NK (CD16(+)) cells (P < 0.001). 1,25 D(3) analogs were more potent than the natural compound: KH1060 up-regulated CD14 expression by SLE monocytes (P < 0.001), inhibited polyclonal and anti-dsDNA IgG production by SLE-derived B lymphoblasts, and induced apoptosis of activated B lymphoblasts. These data suggest that 1,25 D(3) compounds can offer novel approaches to the clinical management of SLE.

Biochemical activities of extracts from Hypericum perforatum L. 5th communication: dopamine-beta-hydroxylase-product quantification by HPLC and inhibition by hypericins and flavonoids.

Extracts from the herb "St. John's wort" (Hypericum perforatum L.) exhibit beneficial effects on patients suffering from mental depressions. Lack of catecholamine neurotransmitters may be one biochemical mechanism for this problem under discussion. It has been recently reported that alcoholic extracts from Hypericum perforatum inhibit dopamine-beta-hydroxylase (D-beta-H) with an I50 of 0.1 mumol/l on the basis of total hypericin content and with an I50 of 21 mumol/l with pure commercial hypericin. As test system polarographic determination of oxygen uptake with tyramine as a substrate analogue was used. In the present paper the quantification of the enzymatic activity and the potential influence of inhibitors are reported using dopamine as substrate and product (noradrenaline) quantification by HPLC. With this test system it could be shown that D-beta-H is strongly inhibited by pseudohypericin (I50 = approx. 3 mumol/l) and hypericin (I50 = approx. 5 mumol/l), whereas the I50-values of various flavonoids (quercitrin, isoquercitrin, hyperoside, rutin, quercetin, amentoflavone, kaempferol) are in the range of 50 mumol/l or higher.

Biochemical model reactions indicative of inflammatory processes. Activities of extracts from Fraxinus excelsior and Populus tremula.

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. All inflammatory processes include such oxygen activating processes where reactive oxygen species (ROS) are produced. Dependent on the strength of these impact(s), 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 vast number of classes of organic molecules including phenolics as the most prominent ones. In this publication the activities of extracts from Fraxinus excelsior, Populus tremula and Solidago virgaurea as components of the drug Phytodolor and their mechanisms of protection from oxidative damage are summarized. In addition, new results on tyrosine nitration, a process characteristic for sites of inflammation, and its inhibition by these plant extracts, is reported.

Effects of long-term administration of vitamin D3 analogs to mice.

This study explores the effects of chronic administration of vitamin D(3) compounds on several biological functions in mice. Knowledge of long-term tolerability of vitamin D(3) analogs may be of interest in view of their potential clinical utility in the management of various pathologies such as malignancies, immunological disorders and bone diseases. Four unique vitamin D(3) analogs (code names, compounds V, EO, LH and LA) and 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)) were administered i.p. for 55 weeks to Balb/c mice. Each analog had previously been shown to have potent in vitro activities. After 55 weeks of administration, the mice had a profound decrease in their serum levels of interleukin-2 (IL-2). Likewise, several analogs depressed serum immunoglobulin G concentrations (compounds LH and LA), but levels of blood lymphocytes and splenic lymphocyte subsets (CD4, CD8 and CD19) were not remarkably depressed. The percent of committed myeloid hematopoietic stem cells was 4- to 5-fold elevated in the bone marrow of the mice that received analogs LH and V; nevertheless, their peripheral blood white and red cell counts and platelets were not significantly different in any of the groups. The mice that received 1,25(OH)(2)D(3) had a decrease in bone quantity and quality with a decrease in cross-sectional area and cortical thickness, and a 50% reduction in both stiffness and failure load compared with the control group. In contrast, the cohort that received a fluorinated analog (compound EO) developed bones with significantly larger cross-sectional area and cortical thickness as well as stronger mechanical properties compared with the control group. At the conclusion of the study, body weights were significantly decreased in all experimental mice. Their blood chemistries were normal. Extensive gross and microscopic autopsy analyses of the mice at the conclusion of the study were normal, including those of their kidneys. In conclusion, the vitamin D(3) analogs were fairly well tolerated. They did suppress immunity as measured by serum IL-2 and may provide a means to depress the immune response after organ transplantation and for autoimmune diseases. Use of these analogs prevented the detrimental effects of vitamin D(3) administration on mechanical and geometric properties of bone, while one analog (compound EO) actually enhanced bone properties. These results suggest that long-term clinical trials with the analogs are feasible.

Antioxidant properties of essential oils. Possible explanations for their anti-inflammatory effects.

Pathogenesis and symptoms of inflammatory processes are accompanied and/or initiated by the production of reactive oxygen species (ROS). The effects of essential oils on these processes have been studied with the aid of biochemical model reactions simulating these pathological events. It can be shown that Myrtol Standardized and Eucalyptus oil ameliorate inflammatory processes by interacting with aggressive oxygen radicals of the OH.-type and interfere with leukocyte activation. These activities partially allow attenuation of oxidative attack and damage introduced by infections or environmental impacts.

Novel therapeutic approach: organic arsenical melarsoprol) alone or with all-trans-retinoic acid markedly inhibit growth of human breast and prostate cancer cells in vitro and in vivo.

The organic arsenical known as melarsoprol (Mel-B) is used to treat African trypanosomiasis. Recently, another arsenical, As2O3 was shown to be effective in treatment of acute promyelocytic leukaemia. We have investigated the anti-tumour activities of Mel-B either with or without all-trans-retinoic acid (ATRA) using the MCF-7 human breast cancer cells, as well as the PC-3 and DU 145 human prostate cancer cells both in vitro and in vivo. The antiproliferative effects of Mel-B and/or ATRA against breast and prostate cancer were tested in vitro using clonogenic assays and in vivo in triple immunodeficient mice. Furthermore, the mechanism of action of these compounds was studied by examining the cell cycle, levels of bcl-2, apoptosis and antiproliferative potency using a pulse-exposure assay. Clonogenic assays showed that the cancer cell lines were sensitive to the inhibitory effect of Mel-B (effective dose that inhibited 50% clonal growth [ED50]: 7 x 10(-9) M for MCF-7, 2 x 10(-7) M for PC-3, 3 x 10(-7) M for DU145 cells. Remarkably, the combination of Mel-B and ATRA had an enhanced antiproliferative activity against all three cancer cell lines. Furthermore, the combination of Mel-B and ATRA induced a high level of apoptosis in all three cell lines. Treatment of PC-3 and MCF-7 tumours growing in triple immunodeficient mice with Mel-B and ATRA either alone or in combination markedly retarded tumour size and weight of the tumours without major side-effects. In conclusion, our results suggest that either Mel-B alone or with ATRA may be a useful, novel therapy for breast and prostate cancers.

Coenzyme Q10, vitamin E, and dihydrothioctic acid cooperatively prevent diene conjugation in isolated low-density lipoprotein.

Coenzyme Q (Q10) and alpha-tocopherol cooperatively delay the onset of diene conjugation in isolated human low density lipoprotein if supplied in water-soluble preparations to blood serum. Both copper ions and morpholino sydnonimine (in the presence of glucose; SIN-1-glucose) -driven diene conjugation is measurable as soon as both reduced Q10 and tocopherol are oxidized, where tocopherol oxidation starts after 80-90% consumption of reduced Q10. LDL-bound Q10 in turn can be rapidly reduced by dihydrolipoic acid (thioctic acid). This reaction is at least 10 times faster than reduction by ascorbic acid.

Evaluation of radical scavenging activity of fresh and air-dried tomatoes by three model reactions.

The radical scavenging activity and the antioxidant content of fresh and air-dried tomatoes were investigated. Tomato halves were dried in a pilot-scale dryer under the following conditions: air temperature, 80 degrees C; air flow rate, 1.5 m/s; drying time, 400 min; final moisture, 25%. Carotenoid (lycopene, beta-carotene, lutein) and ascorbic acid were analyzed by HPLC with a spectrophotometric and an electrochemical detector, respectively. Total phenolics were determined by using the Folin-Ciocalteu reagent. The radical scavenging activity was studied in three model systems: (a) the xanthine oxidase and xanthine system, which generates superoxide radical and hydrogen peroxide; (b) the 3-morpholinosydnonimine system, which releases spontaneously superoxide radical and nitrogen monoxide, forming peroxynitrite; (c) the linoleic acid and CuSO(4) system, which promotes lipid peroxidation. These model systems allow the simulation of key reactions involved in the pathogenesis of certain chronic diseases and may be related to the in vivo activity of tomato antioxidants. Hence, these measurements can be used for optimizing tomato processing and storage. The drying process resulted in a decrease of ascorbic acid content, whereas phenol reagent reducing compounds increased. Carotenoid levels were substantially unchanged upon drying. Fresh and air-dried tomato extracts could act as radical scavengers both in the reactive oxygen species-mediated reactions and in lipid peroxidation. Drying affected the antioxidant effectiveness as measured in the xanthine/xanthine oxidase system, which was found to be the most sensitive method for the measurement of tomato antioxidant activity (lower I(50)) but retained the antioxidant effectiveness in the other two systems.