Biomedical subjects

U Rafałowska

Publications and source records attributed to U Rafałowska.

At least 19 recordsLinked to original sources

PubMed2001

Astroglial reaction during the early phase of acute lead toxicity in the adult rat brain.

The developing nervous system is susceptible to lead (Pb) exposure but less is known about the effect of this toxic agent in adult rat brain. Since astrocytes serve as a cellular Pb deposition site, it is of importance to investigate the response of astroglial cells in the adult rat brain in a model of acute lead exposure (25 mg/kg b.w. of lead acetate, i.p. for 3 days). An increased immunoreactivity of glial fibrillary acidic protein (GFAP) on Western blots was noticeable in fractions of astroglial origin-glial plasmalemmal vesicles (GPV) and in homogenates from the hippocampus and cerebral cortex but not in the cerebellum. The features of enhanced astrocytic reactivity (i.e. large accumulation of mitochondria, activated Golgi apparatus and increment of gliofilaments) were observed in electron microscopy studies in the same tissues. Total glutathione levels increased both in GPV fractions and in brain homogenates-in the cerebellum (120% above control) and in hippocampus (30% above control). The results of current studies indicate that acute lead exposure is accompanied by astrocyte activation connected with the presence of the enhanced expression of GFAP. It may indicate lead-induced neuronal injury. At the same time, a regional enhancement of detoxicative mechanisms (GSH) was noticed, suggesting activation of astrocyte-mediated neuroprotection against toxic Pb action.

Acute Disease↗

PubMed2000

Alteration of dopamine transport and dopamine D(2) receptor binding in the brain induced by early and late consequences of global ischaemia caused by cardiac arrest in the rat.

This study was designed to determine the effects of global cerebral ischaemia caused by temporary cardiac arrest and the early and late consequences of this ischaemia on dopamine transport and dopamine D(2) receptor binding in rat brain. The effects of 10 min of global ischaemia were measured immediately and after 1 h and 7 days post-resuscitation. A decrease of dopamine uptake in the rats by synaptosomes was noted immediately following global ischaemia and 1 h after resuscitation. However, at 7 days post-resuscitation, the dopamine uptake returned to control values. Reversibility of the changes in the synaptosomal dopamine uptake is undoubtedly a favourable sign. Global ischaemia and reperfusion after 1 h or 7 days did not show altered rates of dopamine release but did affect the dopamine D(2) receptor. An observed increase of receptor affinity may be an adaptive response to the reduction in binding capacity. The reduction of visible D(2) receptor binding sites in the early post-resuscitation phase, which was extended to the period of 7 days after resuscitation without recovery, is probably associated with neuronal necrotic damage.

Animals↗

PubMed2000

Acute lead intoxication in vivo affects myelin membrane morphology and CNPase activity.

The aim of the present study was to assess the sensitivity of central nervous system myelin to acute Pb-toxicity in an animal model, that imitates lead toxicity in occupationally exposed workers, or in occasional incidents of poisoning. Our results indicated that in vivo acute lead intoxication affected both the morphology of myelin and enzymatic activity of the myelin marker, CNPase (2'3'-cyclic nucleotide 3'-phosphodiesterase). The multilayered structure of myelin sheaths was regionally disturbed, with loosely arranged membranes or ovoid-shaped swollen fragments. The activity of CNPase was diminished and Michaelis-Menten kinetics showed a decreased affinity and lower velocity of the enzyme. These data suggest that the disturbances in CNPase activity may contribute, in some extent, to the changes in myelin morphology observed in acute Pb-intoxication.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed1999

Inhibition of dopamine transport and binding of [3H] spiperone to dopamine D2 receptor by acute Pb-toxicity in vivo.

Alterations of dopamine transport and binding of [3H] spiperone to dopamine D2 receptor following acute lead intoxication in an in vivo experimental model in adult rats imitate the acute action of Pb2+ in occupationally exposed workers or in occasional incidents of poisoning. The results show that lead-intoxication causes an increased Pb level in blood, a decrease in dopamine uptake and release in synaptosomes and affects the dopamine D2 receptor. These data show that Pb-intoxication may cause severe disturbances in the transport and receptor binding of dopamine, which is involved in the regulation of a variety of functions including locomotor activity, emotion and neuroendocrine secretion.

Acute Disease↗

PubMed1997

Lead-induced abnormalities in blood-brain barrier permeability in experimental chronic toxicity.

The aim of this paper was to determine whether prolonged drinking of lead acetate-containing water by adult rats, which imitates environmental exposure to lead (Pb), affects some morphological and biochemical properties of rat brain microvessels. We noted a significant increase of lead level in capillaries and synaptosomes obtained from brains of rats under chronic toxicity conditions. Intravenously injected horseradish peroxidase (HRP) was used to evaluate the functional state of the blood-brain barrier (BBB). The results indicate that, systematically administered at low doses, lead induces BBB dysfunction. The changes, revealed in light microscopy and confirmed by electron microscopic studies, are typical for "leaky" microvessels, reported for variety of neuropathological conditions associated with BBB damage. Enhanced pinocytotic activity of the endothelial cells and the opening of interendothelial tight junctions, together with enormous phagocytizing action of the pericytes, are the most characteristic ultrastructural features noted. The presence of specific type of perivascular cells containing droplets of lipids in the cytoplasm, together with changes in phospholipid profile in brain capillaries, suggest that altered lipid composition of membranes may, at least in part, be responsible for changes in observed membrane permeability.

Animals↗

PubMed1997

Acute lead toxicity and energy metabolism in rat brain synaptosomes.

Although the neurotoxic effects of lead (Pb) are well documented, the subcellular mechanisms of its action in the central nervous system are not fully understood. The present work examined some parameters of energy metabolism in nerve endings of the brains of adult rats exposed to Pb. We applied the model of acute Pb toxicity in vivo, imitating the acute action of lead observed in occupationally exposed workers or in occasional incidents of poisoning. The measurement of Pb levels in the synaptosomal fraction exhibited its significant accumulation under applied conditions. Oxygen consumption increased in synaptosomes from Pb-treated rats whereas the activity of cytochrome c oxidase did not change. The intrasynaptosomal levels of ATP and CrP were significantly elevated, as was the activity of creatine kinase, suggesting the activation of the CrP/CK system. On the other hand, the activity of the synaptosomal Na+,K(+)-ATP-ase decreased. We suggest that under acute Pb toxicity conditions the mobilization of CrP/CK system may take place to protect the cell against the effects of decreased Na+,K(+)-ATP-ase activity.

Animals↗

PubMed1997

Lead as an inductor of changes in the citrate transport to rat brain synaptic mitochondria.

The aim of the experiments presented here was to discern whether prolonged consumption of leaden water, that imitates environmental exposure, affects citrate transport to synaptic mitochondria. Our results indicate that during chronic lead intoxication both the velocity and the affinity of citrate transport to synaptic mitochondria decreased affecting the operation of Krebs cycle and consequently energetic processes in these mitochondria.

Animals↗

PubMed1996

Effect of acute and chronic lead exposure on the level of sulfhydryl groups in rat brain.

Lead is known to be a potent neurotoxic agent. The interactions of lead with proteins are considered to be at least one of the mechanisms due to which lead exerts its toxicity. In the present work we demonstrate that acute and chronic models of exposure to lead affected the level of total and protein-bound SH groups in homogenates and synaptosomes obtained from rat brains. The concentrations of SH groups were lowered significantly (P < 0.05) in both types of poisoning. Different classes of cellular proteins were considered to play a role in high affinity binding of lead to these ligands.

Animals↗

PubMed1996

Is lead toxicosis a reflection of altered energy metabolism in brain synaptosomes?

The aim of the experiments presented here was to discern whether prolonged consumption of leaden water, that imitates environmental exposure, affects some energetic parameters in nerve endings of adult rat brains. Our results indicated that during chronic lead intoxication the oxidation chain of synaptic mitochondria remains intact. The oxygen consumption by synaptosomes and activity of cytochrom oxidase in synaptic and pericarionic mitochondria obtained from intoxicated rats did not change in comparison to those from the control samples. Compared with the control samples, the concentration of ATP decreased and the concentration of creatine phosphate (CrP) increased drastically in fractions obtained from Pb2+ intoxicated animals with simultaneously increased activity of creatine kinase (CK). It seems likely that, the CrP/Cr/CK system constitutes a satisfactory regulatory mechanism for chronic Pb2+ toxicity effects on energy metabolism in nerve endings of the adult rats.

Adenosine Triphosphate↗

PubMed1994

Lead as an inductor of some morphological and functional changes in synaptosomes from rat brain.

1. The effect of lead (in vivo) on the uptake of GABA, dopamine, and histidine as a precursor of histamine in synaptosomes obtained from chronically lead-treated rats was studied. 2. Lead decreased the uptake of GABA, increased the uptake of dopamine, and did not change the uptake of histidine. These effects were independent of calcium concentration. 3. Lead administration to the rat changed the morphology of the synaptosomes, as manifested in the decreased number of synaptic vesicles and disturbed mitochondrial structure. 4. The results suggest the existence of several mechanisms of lead toxicity on uptake, related to individual neurotransmitters, which are not necessarily connected with a Pb2+/Ca2+ interaction.

Animals↗

PubMed1994

The effect of lead on dopamine, GABA and histidine spontaneous and KCl-dependent releases from rat brain synaptosomes.

The effect of lead on the release of [14C]GABA, [3H]dopamine and [14C]histidine (as a precursor of histamine) was studied in synaptosomes obtained from chronically lead-treated rats and in synaptosomes with in vitro lead added. In vivo treatment of rats with lead acetate results in a decrease in the K(+)-depolarization-dependent release of GABA and dopamine and histidine. Lead given in vitro itself (independently of depolarizing condition) stimulated the release of previously accumulated neurotransmitters in synaptosomes (GABA and dopamine). This effect depends on lead acetate concentration. On the other hand lead, in different concentrations, did not cause changes in the histidine release. The results show that lead can attack the synaptic neurotransmission in two ways: by depressing the Ca-KCl-evoked release of GABA, dopamine and histidine and by a selective stimulation of a spontaneous release (independent of depolarization conditions) of GABA and dopamine but not histidine.

Animals↗

PubMed1991

Peroxidation-induced changes of histamine metabolism and transport of its precursor histidine in rat brain synaptosomes.

The metabolism of histamine and transport of its precursor histidine were investigated in rat brain synaptosomes which underwent the ADP-Fe/ascorbate-induced peroxidation. Peroxidation impaired histidine uptake by 40%, and veratridine induced release of it by 25% of maximal uptake. Simultaneously, marked decrease of synaptosomal histamine (HA) content, to about 30% of control value, was found (p less than 0.01). Activity of the two histamine-metabolizing enzymes, histidine decarboxylase (HD) and histamine N-methyl-transferase (HMT), were drastically lowered, by 40% (p less than 0.02) and 60% of control (p less than 0.05), respectively. Pretreatment of rats with glucocorticoid analog, dexamethasone (DMX), 1 mg/kg of body weight, given twice, 20 and 2 h before decapitation, did not influence significantly the effects invoked by peroxidation on HA levels and the activity of HD and HMT, but impaired histidine transport. These results indicate that iron-dependent peroxidation decreases both neuronal pool of histamine and its turnover, which may affect the function of central nervous system. Short pretreatment with dexamethasone does not seem to influence this effect.

Animals↗

PubMed1991

Effect of hyperoxia on histamine metabolism in rat brain synaptosomes: preliminary observations.

Adult male Wistar rats were submitted to normobaric hyperoxygenation for 1 and 4 hours, then brain synaptosomes were isolated and uptake and release of the histamine precursor - histidine (His), histamine (HA) level and His metabolizing enzymes activities were measured. This uptake in hyperoxic synaptosomes was inhibited by about 20%. After 1-hour hyperoxia, a tendency towards an increase of the HA level, but a significant increase histidine decarboxylase (HD) and histamine methyltransferase (HMT) activities were observed. Four-hour hyperoxia caused a decrease of both the HA level and the activities of both enzymes, especially HMT. The changes were reversed in 1-hour posthyperoxic recovery, except for histidine uptake which remained inhibited.

Animals↗

PubMed1990

Activation of arginine metabolism to glutamate in rat brain synaptosomes in thioacetamide-induced hepatic encephalopathy: an adaptative response?

Crude (P2) synaptosomes derived from rats with acute hepatic encephalopathy (HE) induced with thioacetamide showed a slightly increased uptake of radiolabeled arginine (ARG) and a 2.5-fold enhanced conversion of newly taken-up ARG to both glutamate (GLU) and gamma-aminobutyric acid (GABA) as compared with control synaptosomes. Pulse treatment of the preloaded synaptosomes with a high potassium medium decreased their radioactive GLU and GABA content without affecting the content of the precursor ARG. This result, which was identical with control or HE preparations, appears to indicate that ARG contributes at least, in part, to the synthesis of neurotransmitter GLU or GABA. As measured in purified synaptosomal preparations, HE increased by about 50% the activities of arginase and ornithine-delta-aminotransferase--the two enzymes of the ARG to GLU shunt. It is postulated that increased conversion of ARG to GLU may compensate for excessive utilization of the latter amino acid as an ammonia trap during HE and, as such, may be considered as an adaptative response of the synaptic compartment to this pathological condition.

Acetamides↗

PubMed1989

Effect of in vivo glucocorticoid administration on histamine metabolism in rat brain synaptosomes.

The effect of in vivo administration of acetonide triamcinolone (AT) on histamine (HA) metabolism in synaptosomes, highly purified from rat brain by discontinuous Ficoll-sucrose gradient centrifugation, was investigated. AT decreases ability of synaptosomes to actively accumulate HA precursor, L-[U-14C]histidine, measured after rapid centrifugation of synaptosomes through silicone oil, as well as lowers activity of HA catabolizing enzyme histamine N-methyltransferase (by 57%). In contrast, no changes in the level of HA, assayed by the single isotope enzymatic method, and the activity of HA synthesizing enzyme, histidine decarboxylase, were found. The results indicate that under applied conditions glucocorticoid administration may decrease turnover of neuronal pool of HA without significant effect on HA level.

Animals↗

PubMed1988

Hypoxia and ischemia modifies histamine metabolism and transport in brain synaptosomes.

Histamine level (HA), the activities of the HA synthetizing enzyme--histidine decarboxylase (HD) and HA metabolizing enzyme--histamine methyltransferase (HMT) and the uptake and release of histidine and histamine were analyzed in synaptosomal preparations obtained from rats with brain hypoxia and ischemia. Hypoxia produced only non-significant changes in all the parameters studied, whereas ischemia induced increase of both enzyme activities and histidine release, with simultaneous decreased of histidine uptake and HA level. The effect of ischemia appeared to be reversible; the changes retreated within 1 h of resuscitation together with the vital functions of rats.

Animals↗

PubMed1987

Is neurotransmitter histamine predominantly inactivated in astrocytes?

Rat synaptosomes and astroglia cell-enriched fraction were tested for the uptake of histamine (HA) and its precursor histidine, and the activities of the HA-synthesizing enzyme, histidine decarboxylase (HD) and HA-metabolizing enzyme, histamine methyltransferase (HMT). While histidine uptake was more active into synaptosomes than into astrocytes, only astrocytes were capable of a significant HA uptake. Kinetic analysis of the astrocytic HA uptake revealed a high affinity-low capacity system (Km = 5 X 10(-7) M, Vmax = 1.6 X 10(-12) mol.min-1 X mg-1) similar to the astroglial transport systems for other neurotransmitters. HMT was 70% more active in astrocytes than in synaptosomes, whereas HD activity was not different in these two preparations. The results indicate that astrocytes could be the major site of neurotransmitter HA inactivation.

Animals↗

PubMed1987

Cerebral oxygen consumption in experimental hepatic encephalopathy: different responses in astrocytes, neurons, and synaptosomes.

Oxygen consumption was measured polarographically in fractions enriched in astrocytes or neurons, and in synaptosomes derived from rats in which two subsequent stages of acute hepatic encephalopathy were induced by thioacetamide treatment. A 30% decrease of oxygen consumption was noted in astrocytes from animals with coma, well in agreement with the decrease of whole cerebral oxygen consumption and the increase of whole brain ammonia. In contrast, at the same stage the oxygen consumption in neurons was increased by some 35%, whereas synaptosomes remained unaffected. The results are in keeping with the view that astrocytes are the cells whose metabolism is primarily affected during hepatic encephalopathy. On the other hand, they support recent pathophysiologic evidence that ammonia-induced neuronal dysfunction is not a consequence of impaired energy metabolism in the nerve cells.

Animals↗