Biomedical subjects

G Lupo

Publications and source records attributed to G Lupo.

At least 19 recordsLinked to original sources

PubMed2001

High glucose and advanced glycation end products induce phospholipid hydrolysis and phospholipid enzyme inhibition in bovine retinal pericytes.

In the present study, we investigated the possible role of oxidative stress and the modulation of phospholipid turnover in two related models of pericyte injury, i.e., treatment with high glucose or advanced glycation end products (AGEs). Growing microcapillary pericytes from bovine retinas in culture were incubated, for 3 weeks, with 20-50 mM glucose or 2-20 microM AGEs, and peroxidation parameters (malondialdehyde, conjugated diene, hydroperoxide, glutathione (GSH) levels and lactate dehydrogenase (LDH) release) were evaluated. Arachidonate (AA) and choline release from membrane phospholipids was determined in pericytes prelabeled with [1-(14)C]arachidonate and [Me-(3)H]choline, respectively, and stimulated with elevated glucose or AGEs for 30 min or 2 h. [1-(14)C]arachidonate and [Me-(3)H]choline incorporation into phospholipids, for 2 h and 3 h respectively, was also studied in conditioned and serum-starved cultures. Finally, lysates of treated and control cells were assayed for cytosolic phospholipase A(2) (cPLA(2)), acyl-CoA:1-acyl-sn-glycero-3-phosphocholine O-acyltransferase (AT), CTP:phosphocholine cytidylyltransferase (CT) and microsomal choline phosphotransferase (CPT) enzyme activities. We found that high glucose and AGEs caused neither significant production of reactive oxygen species nor cell toxicity or death, unlike other cell types. Both agents had no significant effect on the cellular ultrastructure, evaluated by light and electron microscopy, AA incorporation and release, cytosolic phospholipase A(2) (cPLA(2)) and AT activities. On the contrary, choline incorporation into phosphatidylcholine, CT and CPT activities were significantly reduced either by 50 mM glucose or 20 microM AGEs. Simultaneously, [Me-(3)H]choline release was significantly stimulated by both agents. We conclude that prolonged treatments with high glucose or AGEs are not able to induce oxidative injury in bovine retinal capillary pericytes. Nevertheless, they do induce phospholipid hydrolysis and phospholipid enzyme activity inhibition.

Animals↗

PubMed2001

Amyloid beta(1-42) and its beta(25-35) fragment induce in vitro phosphatidylcholine hydrolysis in bovine retina capillary pericytes.

We describe the inhibitory effect of full-length Abeta(1-42) and Abeta(25-35) fragment of amyloid-beta peptide on phosphatidylcholine (PtdCho) metabolism in bovine retina capillary pericytes. Cell cultures were incubated with Abetas for 24 h. Peroxidation indices (malondialdehyde and lactate dehydrogenase release) significantly increased after 20-50 microM Abeta(1-42) or Abeta(25-35) treatment. In addition, [Me-3H]choline incorporation into PtdCho strongly decreased while either 3H-choline or 14C-arachidonic acid release from prelabeled cells increased, indicating PtdCho hydrolysis. The effect was very likely due to prooxidant action of both Abeta peptides. Reversed-sequence Abeta(35-25) peptide did not depress 3H-choline incorporation nor stimulate PtdCho breakdown. With addition of Abetas at low concentrations (2-20 microM) to pericytes, marked ultrastructural changes, well connected to metabolic alterations, emerged including shrinkage of cell bodies, retraction of processes, disruption of the intracellular actin network. Cells treated with higher concentrations (50-200 microM) displayed characteristics of necrotic cell death. The data suggest that: (a) Abeta(1-42) and Abeta(25-35) peptides may modulate phospholipid turnover in microvessel pericytes; (b) together with endothelial cells, pericytes could be the target of vascular damage during processes involving amyloid accumulation.

Alzheimer Disease↗

PubMed2001

t-Butyl hydroperoxide and oxidized low density lipoprotein enhance phospholipid hydrolysis in lipopolysaccharide-stimulated retinal pericytes.

Free radicals induced by organic peroxides or oxidized low density lipoprotein (oxLDL) play a critical role in the development of atherosclerosis. In investigating this process, and the concomitant inflammatory response, the role of pericytes, cells supporting the endothelial ones in blood vessels, has received little attention. In this study we tested the hypothesis that tert-butyl hydroperoxide (t-BuOOH) and oxLDL, administered in sublethal doses to the culture medium of retinal pericytes, function as prooxidant signals to increase the stimulation of the peroxidation process induced by lipopolysaccharide (LPS). Confluent cell monolayers were exposed to t-BuOOH (25-400 microM), native LDL or oxLDL (3.4-340 nmol hydroperoxides/mg protein, 1-100 micro). LPS (1 microg/ml), t-BuOOH (200 microM), and oxLDL (100 microM), but not native LDL, incubated for 24 h with cells, markedly increased lipid peroxidation, cytosolic phospholipase A2 (cPLA2) activity and arachidonic acid (AA) release in a time- and dose-dependent manner. AACOCF(3), a potent cPLA2 inhibitor, and the antioxidant alpha-tocopherol strongly inhibited the prooxidant-stimulated AA release. Long-term exposure to maximal concentrations of t-BuOOH (400 microM) or oxLDL (100 microM) had a sharp cytotoxic effect on the cells, described by morphological and biochemical indices. The presence of t-BuOOH or oxLDL at the same time, synergistically increased phospholipid hydrolysis induced by LPS alone. 400 microM t-BuOOH or 100 microM oxLDL had no significant effect on the stimulation of an apoptosis process estimated by DNA laddering and light and electron microscopy. The results indicate that (i) pericytes may be the target of extensive oxidative damage; (ii) activation of cPLA2 mediates AA liberation; (iii) as long-term regulatory signals, organic peroxide and specific constituents of oxLDL increase the pericyte ability to degrade membrane phospholipids mediated by LPS which was used, in the present study, to simulate in vitro an inflammatory burst in the retinal capillaries.

Animals↗

PubMed2001

Expression of the Xvax2 gene demarcates presumptive ventral telencephalon and specific visual structures in Xenopus laevis.

vax2 is a recently isolated homeobox gene, that plays an important role in controlling the dorso-ventral patterning of the retina. In this paper we present a thorough description of the Xvax2 expression pattern all along Xenopus embryogenesis, and compare this pattern in detail to that shown by Xvax1b and Xpax2, two genes also involved in ventral eye development. At early neurula stages, while Xpax2 starts to be expressed within the eye field, both Xvax2 and Xvax1b are exclusively activated in the presumptive ventral telencephalon. Since midneurula stages, Xvax2 and Xvax1b are also transcribed in the medial aspect of the eye field. At tailbud and tadpole stages, Xvax2, Xvax1b and Xpax2 expression overlaps in the optic stalk and nerve and in the optic disk, while Xvax2 and Xvax1b also display specific activation domains in the ventral retina as well as in the ventral telencephalon and diencephalon. Finally, during metamorphosis a high level of both Xvax2 and Xvax1b transcription is maintained in the optic chiasm. In addition, Xvax1b is transcribed in the ventral hypothalamus and in the hypophysis, whereas a strong Xvax2 expression is retained in the ventral portion of the mature retina.

Animals↗

PubMed2000

Xotx5b, a new member of the Otx gene family, may be involved in anterior and eye development in Xenopus laevis.

We describe the cloning, expression pattern and functional overexpression analysis of Xotx5b, a new member of the Otx gene family in Xenopus laevis. Early expression of Xotx5b resembles that of Xotx2, being detected in the organizer region at early gastrula stage, and, shortly after, also in anterior neuroectoderm. During neurula stages Xotx5b exhibits a changing and dynamic pattern of expression. After neural tube closure, Xotx5b is expressed in the eye and pineal gland, both involved in photoreception. Overexpression of Xotx5b has a similar effect to that of Xotx2, producing posterior truncations and inducing ectopic cement gland and neural tissue in whole embryos. In animal cap assays, Xotx5b and Xotx2 are both able to activate XAG, to strongly suppress the expression of the epidermal marker XK81, and to reciprocally activate each other. Finally, in einsteck transplantation assays, Xotx5b is able to respecify a tail/trunk organizer to a head organizer.

Amino Acid Sequence↗

PubMed2000

Homeobox genes in the genetic control of eye development.

Vertebrate eye formation is a complex process which involves early specification of the prospective eye territory, induction events, patterning along the polarity axes and regional specification, to bring about the proper morphogenetic movements, cell proliferation, cell differentiation and neural connections allowing visual function. The molecular machinery underlying such complex developmental events is presently under an intense research scrutiny and many associated genetic factors have been isolated and characterized. These studies produced striking knowledge in the field, especially with respect to uncovering the role of key genes and their possible evolutionary conservation. Presently, a major task is to define the complex interactions connecting the multiplicity of molecular players that regulate eye development. We recently identified two homeobox genes, Xrx1 and Xvax2, and studied their function by using the Xenopus embryo as a developmental model system. Xrx1 and Xvax2 control key aspects of eye development. In particular, Xrx1 appears to play a role in the early specification of anterior neural regions fated to give rise to retina and forebrain structures, and in promoting cell proliferation within these territories. On the other hand, Xvax2 is involved in regulating the eye proximo-distal and/or dorsoventral polarity, and the morphogenetic movements taking place during formation of the optic stalk and cup. Here we review the experimental results addressing the roles of Xrx1 and Xvax2 and their vertebrate orthologues, and discuss their relationship with other molecules also playing a related function in eye development.

Animals↗

PubMed1999

A homeobox gene, vax2, controls the patterning of the eye dorsoventral axis.

We have identified a transcription factor specifically expressed in the developing vertebrate eye. We named this gene vax2 because of the high degree of sequence similarity to the recently described vax1. Both in the human and mouse genomes, vax2 is localized in the vicinity of the emx1 gene. This mapping assignment, together with the previously reported colocalization of Vax1 and Emx2 in mouse, indicates that the vax and the emx genes may be organized in clusters. vax2 has a remarkable expression domain confined to the ventral portion of the prospective neural retina in mouse, human, and Xenopus. The overexpression of either the frog Xvax2 or the human VAX2 in Xenopus embryos leads to an aberrant eye phenotype and, in particular, determines a ventralizing effect on the developing eye. The expression domain of the transcription factor Xpax2, normally confined to the ventral developing retina, extends to the dorsal region of the retina after overexpression of vax2. On the other hand, the expression of Xvent2, a molecular marker of the dorsal retina, is strongly reduced. Furthermore, vax2 overexpression induces a striking expansion of the optic stalk, a structure deriving from the ventralmost region of the eye vesicle. Altogether, these data indicate that vax2 plays a crucial role in eye development and, in particular, in the specification of the ventral optic vesicle.

Amino Acid Sequence↗

PubMed1999

Amyloid beta but not bradykinin induces phosphatidylcholine hydrolysis in immortalized rat brain endothelial cells.

We describe the inhibitory effect of A beta (25-35) fragment of amyloid-beta peptide and bradykinin (BK) on phosphatidylcholine (PtdCho) metabolism in immortalized rat brain GP8.39 endothelial cells (EC). Cultures were incubated either with A beta for 24-48 h, or with BK for 30 min-4 h. The peroxidation indices (malondialdehyde, conjugated dienes) and lactate dehydrogenase (LDH) release significantly increased after A beta peptide (10-50 microM) treatment. The BK (10 microM) stimulation of cells brought about an increase in conjugated dienes and LDH release only after 4 h. Following 24 h treatment with 50 microM A beta peptide, the [Me-3H]choline incorporation into PtdCho strongly decreased while the [3H]choline release increased, indicating PtdCho hydrolysis. The effect was most likely due to peptide prooxidant effect. After 4 h preincubation with BK, the [Me-3H]choline incorporation into PtdCho strongly decreased, but no significant [3H]choline release was found. Following long-term treatment, the action of 50 microM A beta on [3H]choline release was not enhanced by 10 microM BK. Cell exposure to alpha-tocopherol (1 mM) prior to the addition of both agents did not abolish stimulated PtdCho breakdown. The data suggest that: (a) A beta peptide and BK may modulate phospholipid turnover in microvessel cells; (b) they could not synergistically interact in vascular EC damage during processes involving amyloid accumulation and inflammatory response.

Amyloid beta-Peptides↗

PubMed1998

Arachidonate transport through the blood-retina and blood-brain barrier of the rat after reperfusion of varying duration following complete cerebral ischemia.

The permeability-surface area product (PS) of [1-14C]arachidonate at the blood-retina and blood-brain barrier was determined by short carotid perfusion in young Wistar rats 1 or 6 h after recovery period following complete cerebral ischemia induced by temporary cardiac arrest. For the retina and structures of visual system, hypothalamus and olfactory bulb there was no significant difference over sham-operated rats among mean PSs. For cortex, hippocampus and striatum, significant increases were found at both time intervals of recovery after cardiac arrest. The ischemia-reperfusion model was characterized by a significant increase in tissue conjugated diene in the hippocampus and microsomal lysophosphatidylcholine acyltransferase activity in the cortex. Consistent with these findings, we also show ultrastructural evidence mainly represented by partial opening of interendothelial junctions and mild signs of tissue edema in surrounding neuropil, suggesting barrier leakiness predominantly in the cortex, hippocampus and striatum but almost absent in the retina microvessels. Our results indicate that ischemia-reperfusion does affect influex through blood-brain barrier into regional structures of rat central nervous system of arachidonate, a metabolic substrate and lipid mediator rapidly incorporated into microcapillary and brain lipids. The data also suggested that: (i) reactive oxyradicals were moderately generated during the early phase of ischemic-reperfusion process in the rat; (ii) after reperfusion, in vitro susceptibility of different brain regions to iron-induced peroxidation was highest in the hippocampus and lowest in the cortex and striatum; (iii) membrane phospholipid repair mechanisms were activated at the same time.

Acyltransferases↗

PubMed1998

The Xenopus Emx genes identify presumptive dorsal telencephalon and are induced by head organizer signals.

We have isolated and studied the expression pattern of Xemx1 and Xemx2 genes in Xenopus laevis. Xemx genes are the homologues of mouse Emx genes, related to Drosophila empty spiracles. They are expressed in selected regions of the developing brain, particularly in the telencephalon, and, outside the brain, in the otic vesicles, olfactory placodes, visceral arches and the developing excretory system. We also report on experiments concerning the tissue and molecular signals responsible for their activation in competent ectoderm. Xemx genes are activated in ectoderm conjugated with head organizer tissue, but not with tail organizer tissue. Furthermore, they are not activated in animal cap either by noggin or by Xnr3, thus suggesting that a different inducer or the integration of several signals may be responsible for their activation.

Amino Acid Sequence↗

PubMed1996

Phosphatidylcholine synthesis-related enzyme activities of bovine brain microvessels exhibit susceptibility to peroxidation.

In microvessels isolated from bovine brain, microsomal enzyme activities involved in phosphatidylcholine biosynthesis and degradation were determined. The microvessels possessed acyl-CoA:1-acyl-sn-glycero-3-phosphocholine (AT) and glycerophosphocholine phosphodiesterase (GroPChoPDE) activity at a higher level compared with bovine and rat brain or rat liver microsomes whereas they expressed CTP:phosphocholine cytidylyltransferase (CT) and choline phosphotransferase (CPT) activity at a lower level. Each enzyme has been characterized in terms of response to inhibitors or activators revealing properties very similar to those in brain and liver microsomes. In the homogenate prepared from t-butylhydroperoxide-treated microvessels (10 min exposure to 10 microM up to 1 mM concentrations), AT and CPT activities exhibited a significant dose-dependent inhibition. In contrast, GroPChoPDE activity was unaffected. CT was inhibited only at 1 mM concentration. Short treatment of microvessels with Fe2+ (20 microM)-ascorbate (0.25 mM) or 100 microM linoleate hydroperoxide did not have any effect on the activity of the four enzymes. Strong inhibition of all enzymes was noted when the linoleate hydroperoxide system was fortified by Fe2+ ions (100 microM). AT inactivation was also found when oxidized low density lipoprotein was preincubated with microvessels. On the other hand, oxidized LDL left unchanged CPT and GroPChoPDE activities whereas it promoted a slight stimulation of cytidylyltransferase activity. Overall, the results suggest a link between oxygen radical generation and the perturbation of the microvessel membrane structure in which the four enzymes are incorporated, coupled to a direct sulfhydryl protein modification.

Animals↗

PubMed1995

Evidence that phosphatidylserine is imported into mitochondria via a mitochondria-associated membrane and that the majority of mitochondrial phosphatidylethanolamine is derived from decarboxylation of phosphatidylserine.

Phosphatidylserine is synthesized in both the endoplasmic reticulum and a unique membrane fraction, the mitochondria-associated membrane (MAM) (Vance, J.E. (1990) J. Biol. Chem. 265, 7248-7256). In Chinese hamster ovary cells labeled with [3H]serine or [3H]ethanolamine, we found that the majority of mitochondrial phosphatidylethanolamine was derived from phosphatidylserine decarboxylation. Essentially no mitochondrial phosphatidylethanolamine, especially that in the inner membrane, was imported from the endoplasmic reticulum. We tested the hypothesis that phosphatidylserine made in the endoplasmic reticulum is delivered via the MAM to mitochondria for decarboxylation to phosphatidylethanolamine. Cells were pulse-labeled with [3H]serine and subsequently incubated either in the presence of hydroxylamine (for inhibition of phosphatidylserine decarboxylation) or under conditions for which cellular ATP had been depleted (for inhibition of phosphatidylserine import into mitochondria). In hydroxylamine-treated cells, within 2 h, the amount of radiolabeled phosphatidylserine in the MAM and mitochondria, but not microsomes, was greater than in untreated cells. Moreover, in ATP-depleted, but not in control, cells the amount of radiolabeled phosphatidylserine in the MAM approximately doubled by 3 h. These observations are consistent with the hypothesis that newly synthesized phosphatidylserine normally traverses the MAM en route to mitochondria.

Animals↗

PubMed1995

Lipid peroxidation inhibits acyl-CoA:-1-acyl-sn-glycero-3-phosphocholine O-acyltransferase but not CTP: phosphocholine cytidylyltransferase activity in rat brain membranes.

In brain tissue in vivo peroxidized according to three model systems, we determined two microsomal enzyme activities involved in phospholipid biosynthesis. The first, short-term model, was based on the i.v. administration to normal rats, twice a day, for a period of 1 week, of a sonicated emulsion of a peroxidized mixture of phospholipids and linoleate (4:1, w/w; 500 mg/day; hydroperoxides: 200-250 nmol/mg lipid). The half-life time of the injected toxic lipid species in the blood circulation was about 1 h. At the end of the week's treatment, brain and liver malondialdehyde, conjugated diene and lipid hydroperoxide levels were significantly higher in treated rats than in the controls. The second model consisted of the acute injection of aqueous Fe2+ solution (50 mM) into lateral ventricles, and the collection of brain tissue 2 h later. The third model was based on two consecutive injections of hydroperoxylinoleate (1 mg each) into lateral ventricles over a period of 18 h, and the collection of brain tissue 2 h after the second administration. In brain microsomal membranes prepared from peroxide- or iron-treated rats, lysophosphatidylcholine acyltransferase activity exhibited a significant inhibition. On the contrary, in microsomal preparations derived from the short-term model, CTP:phosphocholine cytidylyltransferase activity was slightly stimulated. Intraventricular injection of linoleate or linoleic acid hydroperoxide left this enzyme activity unchanged. The effect of in vitro membrane peroxidation on both microsomal enzyme activities was investigated. By using an Fe2+ (20 microM)-ascorbate (0.25 mM) peroxidation system, the residual acyltransferase and cytidylyltransferase activities were 80 and 72% of initial activity respectively. Significant dose-dependent inactivation of acyltransferase (maximum loss of 45% of initial activity) was seen when 0.1-10 mumol of photooxidized phospholipids were preincubated with 100 micrograms of microsomal membranes. Unoxidized or photooxidized phospholipids (1 mM) promoted a slight stimulation of cytidylyltransferase activity. Altogether, the results suggest a link between oxygen radical generation and the perturbation of the membrane structure in which the enzymes are located.

1-Acylglycerophosphocholine O-Acyltransferase↗

PubMed1995

Evolutionary comparison of enzyme activities of phosphatidylcholine metabolism in the nervous system of an invertebrate (Loligo pealei), lower vertebrate (Mustelus canis) and the rat.

While steady-state kinetic parameters (metabolite pools, Km and activation energies) are partially known for the enzymes involved in phosphatidylcholine synthesis and degradation in mammalian brain, they are not available for the nervous system of lower vertebrates or invertebrates. Since the extent of evolutionary development of an enzyme is not known a priori, we evaluated the kinetic and thermodynamic parameters of choline kinase, CTP:phosphocholine cytidylyltransferase, choline phosphotransferase and glycerophosphorylcholine phosphodiesterase in squid (Loligo pealei) optic lobe, dogfish (Mustelus canis) and rat brain. For all these enzyme activities, basic similarities in Km and inhibitor effect were found. The same was true for the activation energies Ea, with the exception of squid choline kinase and dogfish cytidylyltransferase. Treatment of microsomal membranes with phospholipase C sharply inhibited cytidylyltransferase activity in all three animal species. In dogfish brain, glycerophosphorylcholine phosphodiesterase activity was undetectable. Our results are consistent with the notion that the kinetic properties of the enzyme activities leading to the preservation of the phosphatidylcholine membranous pool may have appeared early in metazoan evolution and been fully conserved in mammals.

Animals↗

PubMed1995

Human tails.

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Humans↗

PubMed1995

A phase I study of intravesical continuous perfusion of recombinant interleukin-2 in patients with superficial bladder cancer.

A Phase I study was started to evaluate the locoregional and/or systemic toxic effects of the continuous perfusion of recombinant interleukin-2 (rIL-2) in superficial bladder cancer. Three different dose levels were used: 3 x 10(6) IU/day (3 patients), 9 x 10(6) IU/day (3 patients) and 27 x 10(6) IU/day (3 patients). Two patients (one treated with 3 x 10(6) and another with 27 x 10(6) IU/day of rIL-2) had hematuria after the end of the treatment, one patient had fever (grade I) and 7 of 9 patients experienced hypotension (grade I-II). All effects were not dose related. Routine laboratory tests indicated that no significant variations of biochemical parameters occurred. A phenotypic analysis of white blood cells detectable in the bladder, showed an evident locoregional activation of lymphoid cells. In particular, T lymphocytes expressed activation antigens (such as CD25 and HLA-DR) following treatment with rIL-2. A 6- to 12-month clinical follow-up, showed that all patients but one (which recurred after 5 months) are alive and disease-free. This therefore indicates that the locoregional perfusion of rIL-2 is safe and gives clinical results similar to those obtained using Calmette-Guérin bacillus locoregional instillation, in patients who underwent a transurethral resection of superficial bladder cancer.

Administration, Intravesical↗

PubMed1994

1-Acyl-2-lysophosphatidylcholine transport across the blood-retina and blood-brain barrier.

The transport of lysophospholipids through the rat blood-retina and blood-brain barrier was determined by using radioactive 1-palmitoyl-2-lysophosphatidylcholine (Pam-lysoPtdCho) and by measuring the uptake of this labeled compound into the retina and various brain regions after short in situ carotid perfusion. The transport was not affected by probenecid (0.25 mM), but it was inhibited, in a dose-dependent manner, by circulating albumin which is able to bind tightly to lysophosphatidylcholine and lowered the availability of the latter for tissue extraction. Radiotracer transfer in the retina was higher than in brain regions. The permeability-surface area products (PS) changed with the inclusion of unlabeled Pam-lysoPtdCho, showing that transport across retinal and brain microvessels is mainly saturable. The data provided an estimate of transport constants (Vmax, Km and non-saturable constant Kd). However, we could not distinguish whether this saturable process represents the saturation of a transport carrier or simple passive diffusion followed by the saturation of enzymatic reactions. In brain tissue lipid extract, 20 s after carotid injection, radiolabel was associated by 45% to unmetabolized Pam-lysoPtdCho. Partial acylation to phosphatidylcholine, as well as hydrolysis and redistribution of the fatty acyl moiety into main phospholipid classes also occurred. The present results, compared to our previous data, indicate that PamlysoPtdCho is transported faster and/or in greater amounts than unesterified fatty acids.

Animals↗

PubMed1994

Lipid hydroperoxides induce changes in palmitate uptake across the rat blood-retina and blood-brain barrier.

The blood-retina and blood-brain transport of fatty acids was studied in control and lipid hydroperoxide-treated rats by measuring the permeability-surface area product (PS) to [1-14C]palmitate. An in situ carotid perfusion method was used. PS values were evaluated: (1) just after intracarotid injection of hydroperoxides; or (2) after a short-term systemic treatment for 1 week with sonicated emulsion of phospholipids-linoleate peroxidized mixture. Compared with saline-treated rats, PS remarkably decreased in the retina and most brain regions studied after acute, arterial injection of hydroperoxide preparations. On the contrary, the transport index significantly increased in the retina and almost all the brain areas after 7 days i.v. treatment with hydroperoxide emulsion. It is suggested that hydroperoxides acutely administered before transport radiotracer brought about a reinforcement of microvasculature junctional area or hampered substrate diffusion across endothelial membrane. On the other hand, upon short-term i.v. administration, hydroperoxides presumably triggered a lipid structure derangement of endothelial cell membranes and zonulae occludens due to their local accumulation and/or high capability of generating oxygen-free radicals.

Animals↗