RESUMEN
Using laboratory experiments, we investigate the influence of water and sediment discharges on the morphology of an alluvial fan. In our flume, a single-thread laminar river deposits corundum sand into a conical fan. We record the fan progradation with top-view images and measure its shape using the deformation of a Moiré pattern. The fan remains virtually self-affine as it grows, with a nearly constant slope. We find that, when the sediment discharge is small, the longitudinal slope of the fan remains close to that of a river at the threshold for sediment transport. Consequently the slope depends on the water discharge only. A higher sediment discharge causes the fan's slope to depart from the threshold value. Due to the downstream decrease of the sediment load, this slope gets shallower towards the fan's toe. This mechanism generates a concave fan profile. This suggests that we could infer the sediment flux that feeds a fan based on its proximal slope.
RESUMEN
When they reach a flat plain, rivers often deposit their sediment load into a cone-shaped structure called alluvial fan. We present a simplified experimental setup that reproduces, in one dimension, basic features of alluvial fans. A mixture of water and glycerol transports and deposits glass beads between two transparent panels separated by a narrow gap. As the beads, which mimic natural sediments, get deposited in this gap, they form an almost one-dimensional fan. At a moderate sediment discharge, the fan grows quasistatically and maintains its slope just above the threshold for sediment transport. The water discharge determines this critical slope. At leading order, the sediment discharge only controls the velocity at which the fan grows. A more detailed analysis reveals a slight curvature of the fan profile, which relates directly to the rate at which sediments are transported.
Asunto(s)
Sedimentos Geológicos , Vidrio , Glicerol , Ríos , Agua , Modelos TeóricosRESUMEN
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes, via its metabolite MPP(+), damages of the nigrostriatal dopaminergic pathway, similar to those observed in Parkinson's disease. An intranigral injection of 10 microg MPP(+) in rat induced a decrease of about 30% of the neuronal dopamine transporter (DAT) activity 21 days after lesion. Based on the hypothesis that MPTP/MPP(+) neurotoxicity involves the nitric oxide (NO) production and/or an activation of poly(ADP-ribose) polymerase (PARP), we investigated the preventive effects of a treatment either with L-Name, a NO synthase (NOS) inhibitor or 3-aminobenzamide, a PARP inhibitor on the reduction of dopamine uptake induced by MPP(+). Rats received a daily injection i.p. of 50 mg/kg L-Name or 10 mg/kg 3-aminobenzamide 3 days before and during 21 days after the MPP(+) lesion. The results showed that inhibitors of NOS and PARP did not prevent the alteration of DAT activity induced by 10 microg MPP(+), indicating that NO and PARP were not involved in the biochemical cascade leading to the inhibition of rat DAT activity by MPP(+) in our experimental conditions.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Glicoproteínas de Membrana , Moduladores del Transporte de Membrana , Proteínas de Transporte de Membrana/antagonistas & inhibidores , Proteínas del Tejido Nervioso , Neuronas/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Trastornos Parkinsonianos/tratamiento farmacológico , Poli Adenosina Difosfato Ribosa/antagonistas & inhibidores , Sustancia Negra/efectos de los fármacos , 1-Metil-4-fenilpiridinio/farmacología , Animales , Dopamina/metabolismo , Dopamina/farmacocinética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Interacciones Farmacológicas/fisiología , Masculino , Proteínas de Transporte de Membrana/metabolismo , Neuronas/enzimología , Fármacos Neuroprotectores/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Trastornos Parkinsonianos/enzimología , Trastornos Parkinsonianos/fisiopatología , Poli Adenosina Difosfato Ribosa/metabolismo , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/metabolismo , Ensayo de Unión Radioligante , Ratas , Ratas Wistar , Sustancia Negra/enzimología , Sustancia Negra/fisiopatología , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismo , TritioRESUMEN
Previous studies have shown that dopamine (DA) uptake was decreased after preincubation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP(+)) in in vitro slice and synaptosome models. The present study, conducted with and without preincubation, attempted to determine whether inhibition results from a direct effect of neurotoxins on neuronal DA transporter or from an alteration of the transporter secondary to other toxic events. DA uptake was inhibited about 50% in the presence of MPTP+O(2) or MPP(+) (0.1, 1 and 5 mM) in rat striatal slices and synaptosomes. Such inhibition was obtained in synaptosomes preincubated for 150 min with MPP(+) and then washed. Inhibition of DA uptake was lower in slices preincubated with MPTP (5 mM)+O(2) and then washed (30%). Experiments in synaptosomes prepared from slices preincubated with MPTP or MPP(+) showed greater inhibition of DA uptake with MPTP. The results suggest that the inhibition of DA uptake in vitro by MPTP or MPP(+) results initially from a direct effect on the transporter during its penetration in nerve endings and subsequently from a transporter alteration related to toxic events. Thus, the preincubation of striatal slices followed by DA uptake measurement in synaptosomes would appear to be a good in vitro model for studying the dopaminergic toxicity of MPTP.
Asunto(s)
1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Sinaptosomas/metabolismo , 1-Metil-4-fenilpiridinio/toxicidad , Animales , Proteínas Portadoras/metabolismo , Cuerpo Estriado/química , Dopamina/farmacocinética , Dopaminérgicos/farmacología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Relación Dosis-Respuesta a Droga , Técnicas In Vitro , Masculino , Modelos Biológicos , Ratas , Ratas Wistar , Sinaptosomas/efectos de los fármacosRESUMEN
Previous experiments reported that an incubation of striatal synaptosomes with 4-hydroxynonenal (4-HNE) resulted in an inhibition of dopamine (DA) uptake and Na+/K+ adenosine triphosphate (ATPase) activity. The present work investigated whether theses inhibitions are related to a 4-HNE binding to the DA transporter (DAT) and the Na+/K+ ATPase. The number of specific [125I]-PE21 binding sites on the DAT was significantly reduced after incubation with 4-HNE. The Na+/K+ ATPase activity decrease induced by 4-HNE was partially reversed, in a dose-dependent manner, by veratridine, a pump stimulator agent. Our previous data (Morel, P., Tallineau, C., Pontcharraud, R., Piriou, A. and Huguet, F., Effects of 4-hydroxynonenal, a lipid peroxidation product, on dopamine transport and Na+/K+ ATPase in rat striatal synaptosomes. Neurochem. Int., 33 (1999) 531-540) combining with the data observed in this study suggest that changes in DA uptake in striatal synaptosomes are directly related to 4-HNE binding to the DAT, whereas the decrease in Na+/K+ ATPase activity resulted only partially from 4-HNE binding to the pump and is mainly secondary to membrane lipid disruption.
Asunto(s)
Adenosina Trifosfatasas/efectos de los fármacos , Aldehído Deshidrogenasa/antagonistas & inhibidores , Aldehídos/farmacología , Proteínas Portadoras/efectos de los fármacos , Proteínas de Transporte de Catión , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Sinaptosomas/efectos de los fármacos , Adenosina Trifosfatasas/metabolismo , Animales , Proteínas Portadoras/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Masculino , Ratas , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio , Sinaptosomas/metabolismo , Veratridina/farmacologíaRESUMEN
The synthesis and in vitro antioxidant activity of 17 new tetraarylpyrroles are investigated by 2 tests highly documented in the literature: capability to prevent Fe(2+)-induced lipid peroxidation on microsomes, which is a membrane preparation rich in polyunsaturated fatty acids, and direct scavenging effect on a stable free radical, 1,l-diphenyl-2-picryl-hydrazyl (DPPH). For the Fe(2+)-induced microsomal lipid peroxidation system, the results show that molecules which possess 2-pyrazinyl or 2-pyridyl in the 3- and 4-positions on the pyrrole ring are the most efficient. Introduction of methoxy groups on the phenyl ring in the 2- and 5-positions increases the effects but the higher activity is obtained with 2-furyl or 2-thienyl. The only compounds which possess a direct scavenger effect on trapping the stable free radical DPPH are those which have 2-pyridyl in the 3- and 4-positions and 2-furyl or 2-thienyl in the 2- and 5-positions.
RESUMEN
Incubation of rat striatal slices induced a large decrease (about 50%) of DA uptake and a slight desialylation of polysialogangliosides (GT1b, GD1b, GD1a) with an increase of monosialogangliosides (GM1). Moreover, a pretreatment of slices by exogenous added neuraminidase of Vibrio cholerae did not modify DA uptake, although the pattern of gangliosides was modified and there was considerable loss (about 45%) of sialic acid in gangliosides and glycoproteins. It was verified that neuraminidase activity occured in synaptic membrane. Thus, DA uptake was apparently not altered by desialylation of plasma membrane carbohydrate conjugates.
Asunto(s)
Metabolismo de los Hidratos de Carbono , Membrana Celular/metabolismo , Cuerpo Estriado/metabolismo , Dopamina/farmacocinética , Ácido N-Acetilneuramínico/metabolismo , Animales , Cuerpo Estriado/efectos de los fármacos , Gangliósido G(M1)/metabolismo , Gangliósidos/metabolismo , Glicoproteínas/metabolismo , Técnicas In Vitro , Masculino , Neuraminidasa/análisis , Neuraminidasa/farmacología , Concentración Osmolar , Ratas , Ratas Wistar , Tritio , Vibrio cholerae/químicaRESUMEN
Aerobically-incubated brain homogenates are known to undergo autoxidation characterized by spontaneous TBARS production, presumably as a result of lipid peroxidation. However, TBARS measurement alone, because of its lack of specificity, is not sufficient to demonstrate the occurrence of lipid peroxidation in complex biological systems. This study, undertaken to determine whether or not spontaneous oxidation of rat brain homogenate is due to lipid peroxidation, measured different specific markers of this process (fatty acids, lipid aldehydes and the formation of fluorescence products) and studied changes in alpha-tocopherol. Incubation of rat brain homogenates at 37 degrees C under air led to spontaneous TBARS formation, which was accompanied by lipid aldehydes and lipid fluorescence products as well as polyunsaturated fatty acid (PUFA) degradation. Alpha-tocopherol was also consumed. On the whole, these results demonstrate that autoxidation of brain homogenate is a spontaneous lipid peroxidation process. When homogenates were exposed to Fe2+ and ascorbic acid-induced oxidative stress, lipid peroxidation was enhanced. However, spontaneous and stimulated peroxidation showed similar patterns not characteristic of classical lipid peroxidation, i.e. without the lag and accelerating phases typical of a propagating chain reaction. PUFA degradation was limited despite stimulation of peroxidation.
Asunto(s)
Ácido Ascórbico/farmacología , Encéfalo/metabolismo , Hierro/farmacología , Peroxidación de Lípido/efectos de los fármacos , Animales , Biomarcadores , Encéfalo/efectos de los fármacos , Ácidos Grasos/aislamiento & purificación , Ácidos Grasos/metabolismo , Fluorescencia , Metabolismo de los Lípidos , Masculino , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Vitamina E/metabolismoRESUMEN
Many recent studies have suggested that oxidative damage is an important factor in several neurodegenerative disorders. Our investigations considered whether autoxidation of rat striatal slices modified dopamine uptake. Biochemical assays (TBARS, MDA-TBA complex, aldehydes, and fluorescent lipid-soluble products) and a [3H]DA uptake assay were performed on nonincubated striatal slices and on slices incubated for 150 min at 37 degreesC in Krebs-Ringer buffer without addition of free-radical generators. The results showed that spontaneous lipid peroxidation occured during incubation and that DA uptake kinetic was biphasic (high-affinity uptake1 and low-affinity uptake2) with a significant decrease of maximal velocity of uptake. Ascorbate, a known antioxidant, was used to determine whether a relationship existed between lipid peroxidation and reduced dopamine uptake. Addition of ascorbate (100 and 500 microM) in Krebs-Ringer buffer for 150 min at 37 degreesC failed to indicate whether decreased [3H]DA uptake resulted from lipid peroxidation. In fact, ascorbate acted as a prooxidant, only preventing decreased DA uptake2 at 100 microM. Trolox, another antioxidant, inhibited lipid peroxidation by about 95% with a concentration of 700 microM and protected only uptake1. With a concentration of 5000 microM, Trolox also protected uptake2. On the whole, these results indicate that spontaneous autoxidation in rat striatal slices was associated with a lipid peroxidation process that altered the DA uptake system.
Asunto(s)
Dopamina/metabolismo , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Neostriado/metabolismo , Proteínas del Tejido Nervioso , Animales , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Proteínas Portadoras/metabolismo , Cromanos/farmacología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Colorantes Fluorescentes , Técnicas In Vitro , Peroxidación de Lípido/fisiología , Masculino , Malondialdehído/metabolismo , Oxidación-Reducción , Terminales Presinápticos/metabolismo , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
As chronic consumption of a diet devoid of n-3 fatty acid induced modification of neurotransmission pathways in the frontal cortex of rats, plasmalogen alteration could occur in this area. Because of the propensity to facilitate membrane fusion, plasmenylethanolamine (PmE), a major plasmalogen of brain, may be involved in synaptic transmission. Female rats were fed diet containing peanut oil [(n-3)-deficient diet] through two generations. Two weeks before mating, half of the female rats of the second generation received a diet containing peanut oil and rapeseed oil (control group). The distribution and acyl composition of major phospholipids, phosphatidylethanolamine and PmE, were measured in the frontal cortex, striatum, and cerebellum of the male progeny of the two groups at 60 d of age. The n-3 polyunsaturated fatty acid (PUFA) deficiency had no effect on the distribution of phospholipids in all brain regions but affected their acyl composition differently. The level of 22:6n-3 was significantly lower and compensated for by higher levels of n-6 fatty acids in all regions and phospholipids studied. However, docosahexaenoic acid, being more concentrated in the PmE of frontal cortex, is also more decreased in the n-3-deficient rats compared to the striatum. By contrast, striatum PmE has retained more 22:6n-3 than PmE of the other regions. In addition, the increase of n-6 PUFA was significantly lower in frontal cortex PmE compared to the striatum and cerebellum PmE. In association with altered neurotransmission observed in frontal cortex of n-3-deficient rats, our results suggest that frontal cortex PmE might be more affected in chronically alpha-linolenic-deficient rats. However, by retaining 22:6n-3, striatum PmE could be most resilient.
Asunto(s)
Química Encefálica , Cerebelo/anatomía & histología , Cuerpo Estriado/anatomía & histología , Grasas Insaturadas en la Dieta/metabolismo , Etanolaminas/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos/metabolismo , Lóbulo Frontal/anatomía & histología , Fosfatidiletanolaminas/metabolismo , Plasmalógenos/metabolismo , Animales , Peso Corporal , Cerebelo/química , Cerebelo/metabolismo , Cuerpo Estriado/química , Cuerpo Estriado/metabolismo , Grasas Insaturadas/química , Ácidos Grasos/química , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Lóbulo Frontal/química , Lóbulo Frontal/metabolismo , Masculino , Tamaño de los Órganos , Fosfatidiletanolaminas/química , Fosfolípidos/química , Fosfolípidos/metabolismo , Plasmalógenos/química , Ratas , Ratas WistarRESUMEN
Lactate accumulation, amino acid aspartate and glutamate levels, and hypoxanthine, xanthine and malondialdehyde (MDA) concentrations were compared in neonate rat brain after transient global hypoxia induced alone or in association with unilateral ligation of a carotid artery. Lactate production in both hemispheres was higher in cerebral hypoxia-ischemia (CHI) than in cerebral hypoxia (CH), and was lower in CHI after 2 h than at 15 min of recovery. Aspartate and glutamate levels were reduced 15 min after CHI in both hemispheres, but aspartate alone was decreased 2 h after CHI in the ipsilateral (left) hemisphere and 15 min after CH in both hemispheres. Hypoxanthine was increased 15 min after CHI in the ipsilateral hemisphere but decreased at 2 h, whereas xanthine was increased. MDA production was not modified after CH or CHI. These data, compared to those obtained in adult animals suggest that glutamate release and the capacity to generate oxygen-derived radicals are lower in neonates after ischemia. These differences might explain why the brain of the mammalian neonate is much more resistant to CH and CHI than that of the adult.
Asunto(s)
Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Metabolismo Energético , Aminoácidos Excitadores/metabolismo , Hipoxia/metabolismo , Animales , Animales Recién Nacidos , Ácido Aspártico/metabolismo , Ácido Glutámico/metabolismo , Hipoxantina/metabolismo , Malondialdehído/metabolismo , Ratas , Ratas Wistar , Xantina/metabolismoRESUMEN
Previous results have shown that modifications of dopamine (DA) high-affinity uptake1 and those of DA low-affinity uptake2 in rat striatal slices were different after autoxidation of this model and in the presence of antioxidants. The aim of this study was to determine whether these two DA uptake systems correspond to two different dopamine transporters or rather to a single one. A lesion into the substantia nigra of animals by injection of 6-hydroxydopamine, a neurotoxic substance of nigrostriatal dopaminergic neurons led to the suppression of both DA uptake systems. These two DA uptake systems were not modified when animals were treated by reserpine or tetrabenazine, which inhibit the vesicular monoamine transporter. Moreover, they were sodium- and temperature-dependent. Experiments with specific inhibitors showed that 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)-piperazine dihydrochloride (GBR-12935) and (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-tolyl ) nortropane chloride (PE2I), two selective DA uptake inhibitors, were significantly more potent than fluoxetine and nisoxetine (selective serotonin and norepinephrine uptake inhibitors respectively) in both DA uptake systems. However, the concentrations of these products inhibiting low-affinity uptake2 by 50% were much greater than those for high-affinity uptake1. Our data indicate that both DA uptake systems are neuronal, independent of the vesicular monoamine transporter, active and specific for dopamine. Our results suggest that high-affinity uptake1 and low-affinity uptake2 correspond to the same dopamine transporter, but would be situated at different levels in the striatal slice model. Uptake1 could take place at the periphery of the slice whereas uptake2 in the depth of the slice.
Asunto(s)
Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Animales , Cuerpo Estriado/efectos de los fármacos , Inhibidores de Captación de Dopamina/farmacología , Fluoxetina/análogos & derivados , Fluoxetina/farmacología , Técnicas In Vitro , Masculino , Actividad Motora/efectos de los fármacos , Norepinefrina/metabolismo , Nortropanos/farmacología , Oxidopamina/farmacología , Piperazinas/farmacología , Ratas , Ratas Wistar , Reserpina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Tetrabenazina/farmacologíaRESUMEN
Several in vitro studies have shown that lactic acidosis plays a role in brain damage by enhancing free radical formation and lipid peroxidation. The purpose of this study was to determine whether gangliosides are affected by lactic acid-induced oxidation in rat brain tissues. Cortical brain slices were incubated at 37 degrees C for 5 or 17 h in Krebs-Ringer buffer containing 20 mM lactic acid (final pH 5.5) previously equilibrated with 100% O2. Damage from lipid peroxidation was estimated by measurement of thiobarbituric acid-reactive substances (TBARS) and analysis of polyunsaturated fatty acids (PUFAs). Gangliosides were studied by high-performance thin-layer chromatography. Incubation with lactic acid induced overproduction of TBARS, whereas PUFAs were only slightly degraded, even after 17 h of incubation. However, the major modifications in the ganglioside profile occurred after 17 h of incubation. Gangliosides GD1a and GT1b decreased in conjunction with a substantial increase in the GM1 percentage. The addition of butylated-hydroxytoluene and desferrioxamine in the incubation medium, or incubation under 100% nitrogen, abolished TBARS production but not the ganglioside modifications, indicating that the change in ganglioside distribution was not related to oxidative stress induced by lactic acid. To investigate the possibility of an enzymatic process activated by the pH shift, slices were incubated with lactic acid in presence of 2,3-dehydro-2-deoxy-N-acetylneuraminic acid, a specific inhibitor of sialidase. In these conditions, no change in gangliosides profile occurred. These results demonstrate that sialidase is responsible for the alterations in the gangliosides composition of rat cortical brain slices during lactic acidosis.
Asunto(s)
Acidosis Láctica/metabolismo , Corteza Cerebral/metabolismo , Gangliósidos/metabolismo , Estrés Oxidativo , Animales , Cromatografía en Capa Delgada/métodos , Radicales Libres , Técnicas In Vitro , Peroxidación de Lípido , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Vitis vinifera cell suspensions were used to isolate and characterize the flavonoids (anthocyanins, catechins) and non-flavonoids (stilbenes) found in red wine. Furthermore, we showed that astringin is produced although this stilbene has not previously been reported to be a constituent of V. vinifera or wine. The ability of these compounds to act as radical scavengers was investigated using 1,1-diphenyl-2-picryl-hydrazyl (DPPH), a stable free radical. Antioxidant activities were assessed by their capacity to prevent Fe2+-induced lipid peroxidation in microsomes and their action on Cu2+-induced lipid peroxidation in low-density lipoproteins. The results showed that astringin has an important antioxidant effect similar to that of trans-resveratrol, and a higher radical scavenger activity than the latter. Astringinin appeared to be more active. These data indicate that phenolic compounds (stilbenes, catechins, anthocyanins) exhibit interesting properties which may account in part for the so-called "French paradox," i.e. that moderate drinking of red wine over a long period of time can protect against coronary heart disease.
Asunto(s)
Antioxidantes/farmacología , Depuradores de Radicales Libres/farmacología , Fenoles/farmacología , Picratos , Rosales/química , Animales , Bepridil/análogos & derivados , Bepridil/farmacología , Compuestos de Bifenilo , Células Cultivadas , Peroxidación de Lípido , Lipoproteínas LDL/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Ratas , Rosales/citología , VinoRESUMEN
We investigated the effects of an OH. (Fe2+/H2O2) generator system on erythrocyte membrane, particularly the time-course of lipid peroxidation as estimated by measurement of conjugated dienes, thiobarbituric reactive substances (TBARS), lipofuscin-like pigments, and alpha-tocopherol. Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (20:4 omega 6) and docosahexenoic acid (22:6 omega 3), were also measured. Erythrocyte membranes were suspended in phosphate buffer containing Fe2+ (200 microM) and H2O2 (1.42 mM), and incubated in a shaking water bath at 37 degrees C. Initially, there was an increase in TBARS and lipofuscin-like pigments, two well-known end products of PUFA oxidative degradation, whereas PUFAs remained unchanged (incubation time: 1 h). After two or more hours of incubation, marked lipid peroxidation was noted, with the appearance of conjugated dienes and a decrease of PUFAs, indicating that lipid peroxidation had occurred after a lag phase during which TBARS were not produced from PUFAs. This suggests that another OH. target was involved.
Asunto(s)
Membrana Eritrocítica/metabolismo , Ácidos Grasos Insaturados/sangre , Radical Hidroxilo/farmacología , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Ácido Araquidónico/sangre , Ácidos Docosahexaenoicos/sangre , Humanos , Peróxido de Hidrógeno , Hierro , Cinética , Lipofuscina/sangre , Vitamina E/sangreRESUMEN
The aim of this study was to determine: 1) the source of Thiobarbituric Reactive Substances (TBARS) spontaneously produced during rat brain homogenate incubation; 2) the cellular components involved; 3) the reason why brain and liver homogenates did not have the same behaviour. Measurements of TBARS, Polyunsaturated Fatty Acids (PUFAs), aldehydes coming from PUFAS breakdown, vitamin E and Schiff's bases levels were performed on brain and liver homogenates, membrane fractions (Mb) and medium containing soluble cytoplasmic components (CS). Mb and CS were prepared by differential centrifugation. Brain homogenate incubation, contrary to liver homogenate, led to an increase in TBARS amount, while PUFAS, aldehydes and vitamin E levels remained unchanged. No TBARS accumulation arose when Mb or CS were separately incubated. However, it was of interest to note that liver or brain incubation of Mb with CS led to an overproduction of TBARS. These results suggested that spontaneous oxidation of brain homogenate was not due to lipid peroxidation. On the other hand, the fact that, contrary to the liver homogenate, liver Mb incubated with CS led to an increase in TBARS level, supports the idea that a "protective agent" was eliminated during centrifugation. It can be speculated that this "agent" is not effective in the brain.
Asunto(s)
Química Encefálica , Hígado/química , Aldehídos/análisis , Animales , Membrana Celular/química , Ácidos Grasos Insaturados/análisis , Hígado/citología , Masculino , Mitocondrias/química , Mitocondrias Hepáticas/química , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Vitamina E/análisisRESUMEN
To investigate the suppressive effect of somatostatin on growth hormone secretion, a consistent, potent stimulus to growth hormone release is required. The antilipolytic compound 3,5-dimethylpyrazole (DMP) gave a rapid rise in plasma immunoreactive growth hormone following iv administration to fasting sheep. The dose response relationship for iv DMP was defined in 12 sheep, and a rise in growth hormone levels from a baseline of 2.1 +/- 0.4 ng/ml (mean +/- SE) to 38.9 +/- 3.9 ng/ml was achieved in 40 min with 0.1 mg/kg bw of DMP given as a bolus. Infusion of graded doses of somatostatin (50, 100 and 200 micrograms) in 4 sheep over a 90 min period resulted in a dose-dependent suppression of the DMP-provoked growth hormone secretion below the responses observed during saline infusion. This experimental model should facilitate further studies of the inhibitory effects of somatostatin, its analogues and other drugs which suppress growth hormone secretion.