RESUMEN
Due to regular challenges of food safety, consumers put high demands on the performance of food quality systems. To deal with these requirements, food manufacturers need effective quality management. Performance of food quality systems can be partly realized by quality assurance systems, such as HACCP (hazard analysis and critical control point), ISO (international organization for standardization), and BRC (british retail consortium). However, it is still unknown to what extent these systems factually contribute to the realization of quality in the wider sense. Therefore, an instrument is needed that measures the effectiveness of quality systems. This article describes the evaluation of instruments on their suitability for the development of a diagnostic instrument that measures the effectiveness of food quality systems. For this evaluation, perspectives of quality, typical characteristics of agrifood production, quantification, and performance measurement of quality management were studied. Instruments that measure the performance of both quality management and production quality were identified and evaluated on the basis of the defined criteria. The criteria for the performance of production quality were 6 quality dimensions, i.e., product quality, availability, costs,flexibility, reliability, and service. The criteria for performance of quality management were analyses of the relationships between quality management, context of the organization, and production quality, a normative procedure, validation, applicability, classification, and a process approach. Finally, for the final instrument, the evaluation resulted in an integrated approach i.e., a technomanagerial approach, and 3 suitable instruments i.e., Wageningen Management Approach, Extended Quality Triangle, and the quality concept of Noori and Radford.
Asunto(s)
Industria de Alimentos/instrumentación , Alimentos , Control de Calidad , Comportamiento del Consumidor , Productos Agrícolas , Estudios de Evaluación como Asunto , Abastecimiento de Alimentos/normasRESUMEN
Profetas (Protein Foods, Environment, Technology and Society) is a Dutch trans-disciplinary research programme, aiming to develop more sustainable food systems. The central theme of the programme is the question: is a transition feasible from a diet based primarily on animal proteins to a diet based for a large part on new food products made from plant proteins? In the programme this question is studied from very different disciplinary perspectives. In the programme a consumer and chain oriented approach is adopted. In the experimental part of the programme, pea proteins are studied. Profetas is funded by the Netherlands Organisation for Scientific Research, with support from the Ministry of Agriculture, Nature management and Fisheries and the food industry. The programme compromises 16 PhD and post-doctoral projects.
Asunto(s)
Industria de Procesamiento de Alimentos/métodos , Pisum sativum/química , Proteínas de Vegetales Comestibles/administración & dosificación , Agricultura , Animales , Comportamiento del Consumidor , Curriculum , Preferencias Alimentarias , Tecnología de Alimentos , Industria de Procesamiento de Alimentos/organización & administración , Humanos , Productos de la Carne , Países Bajos , Investigación , GustoRESUMEN
Consumers' increasing interest in the relationship between diet and health is a sign for food producers to pay more attention to potential health-protecting compounds in new product development and food processing. From a production chain perspective the choice of the raw material that is used is important for the health-protecting potential of the end product. Four apple cultivars (Jonagold, Golden Delicious, Cox's Orange, and Elstar), which can be used as fresh apples or in processed apple products, were compared with regard to flavonol, catechins, phloridzin, and chlorogenic acid concentrations and antioxidant activity. Jonagold apples possessed the highest flavonoid concentration and the highest antioxidant activity. To study seasonal differences, apples from three different harvest years were analyzed, but in three cultivars no effect on flavonoid concentration and antioxidant activity was observed. Long-term storage, both at refrigerator temperature and under controlled atmosphere conditions, was found not to influence flavonoid concentration or antioxidant activity.
Asunto(s)
Antioxidantes/farmacología , Flavonoides , Malus/metabolismo , Fenoles/farmacología , Polímeros/farmacología , Manipulación de Alimentos , Malus/química , Polifenoles , Estaciones del AñoRESUMEN
A rapid in vitro method for measuring antioxidant activity is presented, which enables the evaluation of health claims and the optimization of product development with respect to health protecting compounds. Antioxidant activity is assessed in a system in which lipid peroxidation is induced in male rat liver microsomes by ascorbic acid and FeSO(4). This method has been significantly improved by enabling the use of microtiter plates and an ELISA reader. Large numbers of samples can be analyzed with good reproducibility, which is necessary when dealing with microsomes possessing biological variability. An objective mathematical procedure has been developed to translate data obtained from the lipid peroxidation assay into a value describing the antioxidant activity. As an illustration the method has been applied to measure antioxidant activity of individual flavonoids and apple juice.
Asunto(s)
Antioxidantes/farmacología , Bebidas/análisis , Flavonoides/farmacología , Rosales/química , Animales , Técnicas In Vitro , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Ratas , Ratas WistarRESUMEN
The formation of mutagens after the heating of sugar-casein model systems at 120 degrees C was examined by the Ames test, using Salmonella typhimurium strain TA100. Several sugars (glucose, fructose, galactose, tagatose, lactose, and lactulose) were compared in their mutagenicities. Mutagenicity could be fully ascribed to Maillard reaction products and strongly varied with the kind of sugar. The differences in mutagenicity among the sugar-casein systems were caused by a difference in reaction rate and a difference in reaction mechanism. Sugars with a comparable reaction mechanism (glucose and galactose) showed a higher mutagenic activity corresponding with a higher Maillard reactivity. Disaccharides showed no mutagenic activity (lactose) or a lower mutagenic activity (lactulose) than their corresponding monosaccharides. Ketose sugars (fructose and tagatose) showed a remarkably higher mutagenicity compared with their aldose isomers (glucose and galactose), which was due to a difference in reaction mechanism.
Asunto(s)
Caseínas/farmacología , Disacáridos/farmacología , Hexosas/farmacología , Reacción de Maillard , Mutágenos/farmacología , Salmonella typhimurium/efectos de los fármacos , Pruebas de Mutagenicidad , Salmonella typhimurium/genéticaRESUMEN
The intake of several bioactive components in food products has been associated with lower incidence in various ageing diseases. A group of compounds that is receiving a lot of attention in this respect is the group of natural antioxidants that are present in many food products of plant origin. It is important to know what the effects of processing steps are on the level and activity of these compounds in processed foods. With this information, more accurate figures can be given for epidemiological work. Also product development can be directed to consumer foods with an optimal content and activity of natural antioxidants. Results from studies on the effects of processing on the level and activity of antioxidants in apple and tea are presented as examples of such an approach. A combination of using analytical techniques for the determination of the level of bioactive compounds and in vitro techniques for the determination of the biological activity of the final food product and the intermediate products has been applied. Both decreases as well as increases in the level and activity of antioxidants have been observed depending on the processing conditions. A comparison is made between the measured antioxidant activity of a food product and the predicted activity based on a model taking into account the level and activity of the individual components as determined in the analytical assays. The correlation between these figures is quite good for tea, but for apple juice about 80% of the activity cannot be explained by the measured antioxidants. Matrix effects or the presence of yet unidentified antioxidants in the product can be responsible for this discrepancy.
RESUMEN
This paper discusses possibilities to measure healthiness of a food product. It is argued that besides measurement of concentration of biologically active compounds it is also necessary to measure biological activity of such compounds in a food. In doing so, it becomes possible to substantiate health claims associated with a food, as well as to optimize food processing with respect to healthiness. Two examples are given of measuring bioactivity in a food, antioxidant activity of apple juice, and (anti)mutagenicity of heated milk. It is also stressed that optimization with respect to healthiness should be done taking other quality aspects (such as organoleptic properties, safety and nutritional value) into account.
Asunto(s)
Manipulación de Alimentos , Tecnología de Alimentos , Alimentos , Antimutagênicos/química , Antioxidantes/química , Bioensayo/métodos , Manipulación de Alimentos/métodos , Tecnología de Alimentos/métodos , Fenómenos Fisiológicos de la Nutrición , Factores de TiempoRESUMEN
This research focuses on determining the concentration and antioxidant activity of flavonoids in apples and apple products as a function of storage and processing. The results will be used to optimise apple products with respect to both flavonoid content and antioxidant activity.
Asunto(s)
Manipulación de Alimentos , Frutas/metabolismo , Quercetina/metabolismo , Antioxidantes/metabolismoRESUMEN
Glucosinolates constitute a well-defined group of secondary plant metabolites in cruciferous plants. They occur especially in brassica vegetables, which represent a major part of the human diet. Glucosinolates undergo hydrolysis, catalysed by an endogenous plant enzyme, known as myrosinase, into a range of biological active compounds. Some compounds, for example isothiocyanates, show an anticarcinogenic action by inducing phase II biotransformation enzyme activity (Jongen, Proc. Nutr. Soc. 1996; 55: 433-446). Processing of brassica vegetables influences glucosinolate degradation and therefore the biological activity. We investigate the effects of processing conditions on glucosinolates and their breakdown products. Besides measurement of concentrations also the biological activity of these compounds will be analysed.
Asunto(s)
Manipulación de Alimentos , Glucosinolatos/metabolismo , Verduras/metabolismoRESUMEN
The effect of several tumor promoters (12-O-tetradecanoyl-phorbol-13-acetate (TPA); 1,1'-(2,2,2-trichloroethylidene)bis[4-chlorobenzene] (DDT); Aroclor1260, and clofibrate) on the inhibition of gap junctional intercellular communication (GJIC) and intracellular calcium concentration ([Ca(2+)](i)) was studied in a cell line consisting of initiated cells (3PC). In addition, the effect of different extracellular calcium concentrations ([Ca(2+)](e)) on the effects of tumor promoters on both GJIC and [Ca(2+)](i) were studied. Agents with GJIC inhibiting capacity increased [Ca(2+)](i). However, the increase of [Ca(2+)](i) did not (always) precede GJIC inhibition. The effect of tumor promoters on GJIC were similar under low (0.05 mM) and high (1.20 mM) Ca(2+)(e) conditions, while different effects on [Ca(2+)](i) were found. These results suggest that tumor promoters can inhibit GJIC and change [Ca(2+)](i), but that there is no direct relationship between these two processes.
RESUMEN
Differences in calcium-mediated regulation of gap junctional intercellular communication (GJIC) between a cell line consisting of mouse epidermal initiated cells (3PC) and a mouse epidermal carcinoma-derived cell line (CA3/7) were studied. Under low extracellular calcium ((Ca2+)e) conditions (0.05 mM) CA3/7 cells showed a low level of GJIC compared with 3PC cells. High (Ca2+)e (1.20 mM) raised GJIC between CA3/7 cells to the GJIC level of 3PC cells, which in turn remained unchanged under these conditions. Raising the free intracellular calcium concentration ((Ca2+)i), using a calcium ionophore (ionomycin) or the Ca2+-ATPase inhibitor thapsigargin under low (Ca2+)e conditions, did not affect the GJIC level between 3PC cells, and increased GJIC between CA3/7 cells. Intracellular calcium chelation in 3PC cells under low (Ca2+)e conditions by ethylene glycol-bis(beta-amino-ethyl ether) N,N,N',N'-tetra-acetic acid acetoxy-methyl ester (EGTA-AM) decreased GJIC in this cell line. High (Ca2+)e conditions protected both cell lines from a decreased GJIC by EGTA-AM exposure. Inhibition of calmodulin (CaM) by calmidazolium (CDZ) or N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7) under low (Ca2+)e conditions, inhibited GJIC in 3PC cells and increased GJIC in CA3/7 cells. Inhibition of Ca2+/CaM-dependent protein kinase (Ca2+/CaM-PK) by 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-7) decreased GJIC in both cell lines. Western analysis showed that Cx43 was more phosphorylated in both cell lines in concurrence with different effects on the GJIC level. Under conditions in which GJIC was inhibited, a decreased immunostaining of Cx43 on the plasma membrane was found. The level of immunostaining of the cell adhesion molecule E-cadherin on the plasma membranes of both cell types remained unchanged under conditions in which GJIC was changed by modulaters of (Ca2+)i, CaM activity, or the Ca2+/CaM-PK activity. These results indicate that differences exist between 3PC cells and CA3/7 cells in the GJIC regulation by intracellular calcium and calmodulin.
Asunto(s)
Calcio/fisiología , Comunicación Celular/fisiología , Células Epidérmicas , Uniones Comunicantes/fisiología , Neoplasias Cutáneas/patología , Animales , Cadherinas/metabolismo , Cadherinas/fisiología , Calcio/farmacología , Calmodulina/metabolismo , Calmodulina/fisiología , Línea Celular , Conexinas/metabolismo , Conexinas/fisiología , Epidermis/metabolismo , Ratones , Fosforilación , Neoplasias Cutáneas/metabolismo , Células Tumorales CultivadasRESUMEN
We recently reported that tumor necrosis factor alpha is able to cause a dose-dependent and persistent reduction in gap junctional intercellular communication between primary human smooth muscle cells. In order to study whether this observed persistent reduction in gap junctional intercellular communication is a unique feature for tumor necrosis factor alpha, the present study focuses on the effects of other growth factors and cytokines on gap junctional intercellular communication. Platelet-derived growth factor AA and BB (PDGF-AA, PDGF-BB), basic fibroblast growth factor (bFGF), interleukin-6 and interferon-gamma were able to modulate gap junctional intercellular communication between primary human smooth muscle cells in vitro. However, our results demonstrate that the magnitude and nature of the observed effects are growth factor- and cytokine-specific. PDGF-AA, PDGF-BB and interleukin-6 caused a transient reduction in gap junctional intercellular communication, while bFGF induced a transient increase in gap junctional intercellular communication. Interferon-gamma was shown to be capable of causing a persistent reduction in gap junctional intercellular communication. In addition, PDGF-AA, PDGF-BB, bFGF, interleukin-6, interferon-gamma and tumor necrosis factor alpha all stimulated smooth muscle cell proliferation. These observations suggest a more complex relationship between modulation of gap junctional intercellular communication and cell proliferation than current hypotheses imply. The implications of the observed effects of growth factors and cytokines on gap junctional intercellular communication between smooth muscle cells in relation to the process of atherosclerosis is discussed.
Asunto(s)
Comunicación Celular/efectos de los fármacos , Uniones Intercelulares/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/farmacología , Arteriosclerosis/inducido químicamente , Arteriosclerosis/etiología , Becaplermina , Comunicación Celular/fisiología , Células Cultivadas/efectos de los fármacos , Factores de Crecimiento de Fibroblastos/farmacología , Humanos , Uniones Intercelulares/fisiología , Interferón gamma/farmacología , Interleucina-6/farmacología , Proteínas Proto-Oncogénicas c-sis , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) and benzoyl peroxide (BoP) on gap junctional intercellular communication (GJIC) and the amount and localization of E-cadherin was studied in initiated mouse epidermal cells (3PC) and in carcinoma cells (CA3/7) originating from the same cell type. In addition, the localization and phosphorylation of connexin43 was studied in both cell lines and in primary keratinocytes. GJIC inhibition by TPA and BoP was stronger in primary keratinocytes compared with both cell lines. BoP strongly decreased the amount of E-cadherin protein and the level occurring in the membranes in both cell lines, whereas TPA caused a translocation of E-cadherin from the membrane towards the cytosol, without decreasing the total amount of E-cadherin present. The effect of both tumor promoters on connexin43 phosphorylation and localization was agent as well as cell dependent. These results show for the first time that tumor promoters can decrease the quantity and membrane localization of E-cadherin in different cell types.
Asunto(s)
Peróxido de Benzoílo/farmacología , Cadherinas/metabolismo , Carcinógenos/farmacología , Comunicación Celular/fisiología , Uniones Comunicantes/fisiología , Acetato de Tetradecanoilforbol/farmacología , Animales , Cadherinas/efectos de los fármacos , Comunicación Celular/efectos de los fármacos , Línea Celular , Membrana Celular/metabolismo , Células Cultivadas , Conexina 43/metabolismo , Citosol/metabolismo , Uniones Comunicantes/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Queratinocitos/fisiología , Ratones , Fosforilación , Células Tumorales CultivadasRESUMEN
The effects of the glycoalkaloids alpha-solanine, alpha-chaconine and alpha-tomatine on different cell types were studied in order to investigate the membrane action of these compounds. Hemolysis of erythrocytes was compared to 6-carboxyfluorescein leakage from both ghosts and erythrocyte lipid vesicles, whereas leakage of enzymes from mitochondria and the apical and baso-lateral side of Caco-2 cells was determined. Furthermore, the effects of glycoalkaloids on the gap-junctional communication between Caco-2 cells was studied. From these experiments, it was found that glycoalkaloids specifically induced membrane disruptive effects of cholesterol containing membranes as was previously reported in model membrane studies. In addition, alpha-chaconine was found to selectively decrease gap-junctional intercellular communication. Furthermore, the glycoalkaloids were more potent in permeabilizing the outer membrane of mitochondria compared to digitonin at the low concentrations used.
Asunto(s)
Permeabilidad de la Membrana Celular/efectos de los fármacos , Membrana Celular/fisiología , Colesterol , Alcaloides Solanáceos/farmacología , Adenilato Quinasa/metabolismo , Animales , Células CACO-2 , Digitonina/farmacología , Membrana Eritrocítica , Eritrocitos , Fluoresceínas , Colorantes Fluorescentes , Uniones Comunicantes/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , L-Lactato Deshidrogenasa/metabolismo , Masculino , Mitocondrias Hepáticas/fisiología , Ratas , Ratas WistarRESUMEN
The effects of five non-mutagenic carcinogens--Aroclor 1260, benzoyl peroxide (BP), phenobarbital (PB), 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 1,1'-(2,2,2-trichloroethylidene)bis[4-chlorobenzene] (DDT)--on gap junctional intercellular communication (GJIC) were tested in a cell line consisting of initiated cells (3PC). Four agents suspected of tumor promotion activity--o-anisidine, clofibrate, L-ethionone and d-limonene--were also tested for their effects on GJIC. Finally sodium fluoride (NaF), whose carcinogenic property is still unclear, was tested for its effects on GJIC in the 3PC cell line. Four of the five selected tumor promoters (Aroclor 1260, BP, DDT and TPA) decreased GJIC between these initiated epidermal cells. The four non-mutagenic carcinogens with tumor-promoting activity in vivo (o-anisidine, clofibrate, L-ethionine and d-limonene) all inhibited GJIC, whereas NaF had no effect. Seven compounds (o-anisidine, Aroclor 1260, BP, DDT, L-ethionine, d-limonene and TPA) had a dose-dependent as well as time-dependent inhibitory effect on GJIC. Under the experimental conditions used, clofibrate showed only a dose-related inhibition of GJIC. PB showed no inhibitory effect on GJIC in the 3PC cell line. In order to determine the role of biotransformation in the tumor-promoting activity of PB, its effect on GJIC was also examined in the presence of an Aroclor 1254-induced rat liver homogenate (S9 mix) and in the hepatoma cell line HepG2. In the presence of rat liver homogenate PB decreased GJIC in the 3PC cell line, whereas in the HepG2 cells PB showed a time- and dose-dependent inhibitory effect. To study the potential differences in susceptibility of cells representing different stages in the process of tumor formation, the effect of the selected tumor promoters on GJIC was also investigated in primary mouse keratinocytes and in a mouse skin carcinoma-derived cell line (CA3/7). Primary keratinocytes were sometimes more (BP and clofibrate) and sometimes less sensitive (ethionine and limonene) for inhibitory effects on GJIC compared to the effects in the cell line 3PC. Except for TPA and anisidin, GJIC between the CA3/7 cells was less affected by the selected agents compared to the 3PC cell line. These results show that, during the process of tumor formation the susceptibility of cells to inhibition of GJIC by tumor promoters is variable. Overall the CA3/7 cells are less sensitive compared to 3PC cells. The susceptibility of primary keratinocytes is variable compared to 3PC cells, depending on the agent used. These results also show that GJIC is a valid parameter for testing the tumor-promoting activity of compounds. Finally, this study demonstrates that mouse keratinocyte cell lines could serve as an in vitro model for the detection of non-mutagenic carcinogens with diverse target organs in vivo. For this use the cell line consisting of initiated cells (3PC) is more sensitive than the carcinoma-derived cell line CA3/7.
Asunto(s)
Comunicación Celular/efectos de los fármacos , Uniones Intercelulares/efectos de los fármacos , 9,10-Dimetil-1,2-benzantraceno , Animales , Arocloros/toxicidad , Peróxido de Benzoílo/metabolismo , Peróxido de Benzoílo/toxicidad , Biotransformación , Calcio/farmacología , Carcinógenos/toxicidad , Diferenciación Celular/efectos de los fármacos , Línea Celular , Ciclohexenos , DDT/toxicidad , Queratinocitos/efectos de los fármacos , Limoneno , Ratones , Fenobarbital/toxicidad , Ratas , Terpenos/farmacología , Acetato de Tetradecanoilforbol/toxicidad , Células Tumorales CultivadasRESUMEN
In this study the interaction between the glycoalkaloids alpha-chaconine, alpha-solanine and alpha-tomatine and sterols in model membranes was analysed systematically using techniques like membrane leakage, binding experiments, detergent extraction, electron microscopy, NMR and molecular modelling. The most important properties for sterols to interact with glycoalkaloids turned out to be a planer ring structure and a 3 beta-OH group, whereas for alpha-chaconine the 5-6 double bond and the 10-methyl group were also of importance. The importance of sugar-sugar interactions was illustrated by the high synergistic effect between alpha-chaconine and alpha-solanine, the leakage enhancing effect of glycolipids, and the almost complete loss of activity after deleting one or more mono-saccharides from the glycoalkaloids. The formed complexes which were resistant against detergent extraction existed of glycoalkaloid/sterol in a 1:1 ratio and formed tubular structures (alpha-chaconine) with an inner monolayer of phospholipids, whereas with alpha-tomatine also spherical structures were formed. Based on the results a molecular model for glycoalkaloid induced membrane disruption is presented.
Asunto(s)
Membranas Artificiales , Solanina/análogos & derivados , Solanina/química , Tomatina/química , Secuencia de Carbohidratos , Espectroscopía de Resonancia Magnética , Microscopía Electrónica , Modelos Moleculares , Datos de Secuencia Molecular , Esteroles/químicaRESUMEN
Inhibition of intercellular communication is an important feature in the tumour promotion phase of a multistage carcinogenesis model. In atherosclerosis inhibition of cell-cell communication by atherogenic compounds, e.g., low density lipoproteins (LDL), also seems to be important. For testing atherogenic compounds we used an atherosclerosis relevant cell type, namely human smooth muscle cells. In order to investigate which part of the LDL particle would be involved in inhibition of metabolic co-operation between human smooth muscle cells in culture we tested several fatty acids and their breakdown products, namely aldehydes. Unsaturated C-18 fatty acids markedly influenced gap-junctional intercellular communication (GJIC), whereas saturated (C18:0, C16:0) and unsaturated fatty acids with > 20 carbon atoms did not inhibit GJIC. In the case of oleic and elaidic acid, orientation seemed important; however, after exposure to palmitoleic and palmitelaidic acid no differences were found. The most potent inhibitor of GJIC was linoleic acid, which inhibited GJIC by 75%. No correlation was found between degrees of unsaturation and ability to inhibit GJIC. Of the tested aldehydes, hexanal, propanal, butanal and 4-hydroxynonenal did significantly inhibit GJIC, while pentanal had no effect. Since modification of LDL was shown to be important in order for LDL to inhibit GJIC, these results show that fatty acids and their oxidative breakdown products may be of importance for the inhibition of GJIC by LDL.
Asunto(s)
Aldehídos/farmacología , Comunicación Celular/efectos de los fármacos , Uniones Intercelulares/efectos de los fármacos , Lipoproteínas LDL/farmacología , Músculo Liso Vascular/efectos de los fármacos , Células Cultivadas , Ácidos Grasos/farmacología , Humanos , L-Lactato Deshidrogenasa/metabolismo , Músculo Liso Vascular/citologíaRESUMEN
In this study the effects of the glycoalkaloids alpha-solanine, alpha-chaconine, alpha-tomatine and the aglycone solanidine on model membranes composed of PC in the absence and presence of sterols have been analysed via permeability measurements and different biophysical methods. The main result is that glycoalkaloids are able to interact strongly with sterol containing membranes thereby causing membrane disruption in a way which is specific for the type of glycoalkaloid and sterol. For this dual specificity both the sugar moiety of the glycoalkaloid and the side-chain of the sterol on position 24 turned out to be of major importance for the membrane disrupting activity. The order of potency of the glycoalkaloids was alpha-tomatine > alpha-chaconine > alpha-solanine. The plant sterols beta-sitosterol and fucosterol showed higher affinity for glycoalkaloids as compared to cholesterol and ergosterol. The mode of action of the glycoalkaloids is proposed to consist of three main steps: (1) Insertion of the aglycone part in the bilayer. (2) Complex formation of the glycoalkaloid with the sterols present. (3) Rearrangement of the membrane caused by the formation of a network of sterol-glycoalkaloid complexes resulting in a transient disruption of the bilayer during which leakage occurs.
Asunto(s)
Membrana Celular/efectos de los fármacos , Alcaloides Solanáceos/farmacología , Esteroles/metabolismo , Rastreo Diferencial de Calorimetría , Secuencia de Carbohidratos , Membrana Celular/metabolismo , Diosgenina , Técnica de Fractura por Congelación , Membrana Dobles de Lípidos , Microscopía Electrónica , Datos de Secuencia Molecular , Solanina/análogos & derivados , Solanina/farmacología , Especificidad por Sustrato , Tomatina/farmacologíaRESUMEN
4-chloro-methoxyindole is a naturally occurring compound in Vicia faba which can easily react with nitrite to form a N-nitroso compound. In this in vitro study, the potential genotoxic effects of nitrosated 4-chloro-6-methoxyindole and its structural analogue 4-chloroindole were evaluated for the first time by using both Salmonella and Chinese hamster V79 cells. Additionally, the inhibition of gap junctional intercellular communication in V79 cells by these compounds was determined; this is a validated parameter for tumor-promoting activity. Most assays were also performed with nitrosated indole-3-acetonitrile, a naturally occurring compound in brassicas. Both nitrosated chloroindoles were highly mutagenic to Salmonella typhimurium TA100 without the need of exogenous metabolic activation and were potent inducers of Sister Chromatid Exchanges. Nitrosated indole-3-acetonitrile generated the same effects, although at much higher concentrations. Equivocal results were obtained for the nitrosated chloroindoles in a forward mutation assay using the hypoxanthine guaninephosphoribosyltransferase locus. All nitrosated indole compounds significantly inhibited gap junctional intercellular communication. These results indicate that nitrosated chloroindoles and nitrosated indole-3-acetonitrile should be considered as mutagens and agents with potential tumor-promoting capacity.