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Biomedical subjects

G Benzi

Publications and source records attributed to G Benzi.

At least 91 records · Page 5Linked to original sources
PubMed1989

Experimental subarachnoid hemorrhage. Lipid peroxidation and Na+,K(+)-ATPase in different rat brain areas.

Subarachnoid hemorrhage (SAH) was produced in Sprague Dawley rats by injection of 0.30 mL of autologous arterial blood into the cisterna magna. Tissue lipid peroxide, quantified as thiobarbituric acid reactive material (TBAR), and Na+,K(+)-ATPase activity were assayed in three different rat brain areas (cerebral cortex, hippocampus, and brain stem) of sham-operated rats and in four hemorrhagic rat groups at 30 min, 1 h, 6 h, and 2 d after SAH. Na+,K(+)-ATPase activity decreased in the cerebral cortex at 30 min, 1 h, and 6 h and in the brain stem at 1 h after SAH induction, whereas enzymatic activity was unchanged in the hippocampus. There was no evident difference in lipid peroxide content between sham-operated animals and hemorrhagic animals. These results indicate that little modifications in lipid peroxidative process (as expressed in TBAR) are not responsible for changes in the ATPase activity.

Animals↗
PubMed1989

Relationship between aging, drug treatment and the cerebral enzymatic antioxidant system.

Four different brain regions (parieto-temporal cortex, caudate-putamen, substantia nigra, and thalamus) were examined in rats aged 5, 10, 15, 20, 25, 30, and 35 months. The following enzyme activities related to the antioxidant system were measured: glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione peroxidase, glutathione reductase, and superoxide dismutase (as total). Specific enzyme activities vary markedly with age, according to the various regions studied, indicating nonhomogenous vulnerability of different brain regions to aging. In general, both superoxide dismutase and glutathione reductase tended to decline during the last half of life, while glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase tended to increase slightly with age. In rats of 10, 20, or 30 months, chronic treatment for two months with a vasodilator (papaverine) or a calcium-blocker (nicardipine) indicated that the antioxidant enzyme activities are partially influenced according to the exogenous agent used, the brain region tested, and the age of the animals.

Aging↗
PubMed1989

Cerebral enzyme antioxidant system. Influence of aging and phosphatidylcholine.

To obtain a comprehensive profile of the age-related changes of the antioxidant enzyme system in discrete brain regions (cortex, caudate-putamen, substantia nigra, thalamus), the present study involved practically the total life span of male Wistar rats (from 5 to 35 months of age). The activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase increase from 5 to 25 months of life and remain relatively constant or decrease scantily thereafter. In thalamus, the activity of total superoxide dismutase (SOD) increases from 5 to 20 months of rat life and decreases thereafter. Conversely, in both substantia nigra and caudate-putamen, enzyme activity declines steadily with age, while in parietotemporal cortex enzyme activity deteriorates from the 25th month onward. In both caudate-putamen and parietotemporal cortex, the activity of glutathione peroxidase increases from 5 to 20 months of life and remains relatively constant thereafter, while in substantia nigra the enzyme activity is practically unmodified during the life span. Furthermore, the activity of glutathione reductase in parietotemporal cortex declines from the 20th month onward, while in caudate-putamen and thalamus, enzyme activity deteriorates after an increase from 5 to 20 months of life. The interference of phosphatidylcholine and/or its metabolite(s) with the cerebral enzyme antioxidant system shows a characteristic specificity as regards both the time of onset and the enzyme activities involved, namely, SOD and glutathione reductase. The interference with SOD is related to the cytosolic form of the enzyme and affects the cortex only of 5-month-old animals and also extends to the thalamus of 15-month-old rats and all regions in 25-month-old ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Effects of nicardipine on the ex vivo release of eicosanoids after experimental subarachnoid hemorrhage.

The activation of lipid peroxidation and the enhancement of arachidonic acid metabolism have been demonstrated as indicators of brain damage after subarachnoid hemorrhage (SAH). Meanwhile, the final common pathway of neuronal damage seems to be related to the impaired homeostasis of Ca++. The present study evaluated the effect of the calcium-antagonist nicardipine on arachidonate metabolism after experimental induction of SAH. The ex vivo release of four eicosanoids (prostaglandin (PG)D2, PGE2, 6-keto-PGF1 alpha, and leukotriene (LT)C4) was measured at different intervals after SAH induction. Rats were separated into the following three groups: a sham-operated group, an SAH group (rats were injected with 0.3 ml autologous arterial blood), and an SAH-treated group (after SAH induction, rats were treated with nicardipine 1.2 mg/kg intraperitoneally). Nicardipine significantly decreased the ex vivo release of PGD2 at 48 hours after SAH (p less than 0.01). The release of PGE2 was significantly enhanced at 6 hours after SAH, while in the nicardipine-treated group PGE2 release is significantly reduced. Nicardipine also affects the lipoxygenase pathway, reducing the release of LTC4 at 1, 6, and 48 hours after SAH induction. The results of the present study show that nicardipine treatment exerts an inhibitory effect on both biochemical pathways of arachidonic acid metabolism; aside from vascular effects, nicardipine could exert a protective role against the release of arachidonate metabolites, which could play a significant role in the pathogenesis of brain damage after SAH.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Action of L-acetylcarnitine on age-dependent modifications of mitochondrial membrane proteins from rat cerebellum.

Protein patterns of mitochondrial outer membrane, inner membrane, and matrix from non-synaptic (free) mitochondria from rat cerebellum at different ages (4, 8, 12, 16, 20, and 24 months) were analyzed by gel electrophoresis. Acute L-acetylcarnitine treatment was performed by a single i.p. injection (100 mg/kg body weight) of the substance 60 min before the sacrifice of the animals. Different age-dependent changes were obtained for the proteins of the three fractions. The amount of some protein subunits increased and/or decreased after drug treatment. In particular, protein composition of the inner mitochondrial membrane showed significant age-related modifications. This result probably indicates differences in protein synthesis and/or turnover rates in the various mitochondrial compartments during aging. Acute L-acetylcarnitine treatment caused: a high increase in the amount of one inner membrane protein with Mw 16 kDa, at all the ages studied; a decrease in the amount of many other inner membrane proteins; modifications of some matrix proteins. Our results show that in vivo administration of L-acetylcarnitine affects mainly the inner membrane protein composition of cerebellar mitochondria.

Acetylcarnitine↗
PubMed1988

Changes induced by aging and drug treatment on cerebral enzymatic antioxidant system.

The age-related modifications of the participants to the cerebral enzymatic antioxidant system (superoxide dismutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase) were evaluated in four brain regions from male Wistar rats aged 5, 10, 15, 20, 25, 30, and 35 months. Both the specific enzyme activity and the profile of any enzyme tested markedly differ with age according to the region examined: parieto-temporal cortex, caudate-putamen, substantia nigra and thalamus. This inhomogeneous age-related profile of enzyme activities could explain both the controversial data of literature and the different regional vulnerability of the brain tissue to damage with aging. In rats aged 10, 20, or 30 months, the chronic i.p. treatment for two months with papaverine or ergot alkaloids (dihydroergocristine, dihydroergocornine, dehydroergocriptine) suggests that the antioxidant enzyme activities may be influenced according to the agent utilized, the brain region tested, and the age of the animal. In any case, small differences in the drug structure support marked differences in the type and extent of the intervention on the antioxidant enzymatic system.

Aging↗
PubMed1988

Bioenergetics of different brain areas after experimental subarachnoid hemorrhage in rats.

We studied energy metabolism after experimental subarachnoid hemorrhage in rats. Four different cerebral areas were tested: frontal cortex, occipital cortex, hippocampus, and brainstem. Vmax of the following enzymatic activities was evaluated: in the homogenate: hexokinase, phosphofructokinase, and lactate dehydrogenase for the glycolytic pathway, and glucose-6-phosphate dehydrogenase for the hexose monophosphate shunt; in the purified nonsynaptic mitochondria: NAD+-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase for the Krebs cycle, and cytochrome oxidase for the electron transfer chain. We also evaluated some parameters related to the respiration of nonsynaptic mitochondria (State 3, State 4, uncoupled state, respiratory control ratio, and ADP:O ratio). Subarachnoid hemorrhage did not significantly affect Vmax of the enzymatic activities related to anaerobic and aerobic metabolism; however, mitochondrial respiration was affected, particularly in the presence of NADH-producing substrates (glutamate + malate).

Adenosine Diphosphate↗
PubMed1987

Phenobarbital and 6-aminonicotinamide effect on cerebral enzymatic activities related to energy metabolism in different rat brain areas.

The effect of phenobarbital (100 mg/kg i.p.) and 6-aminonicotinamide (6AN) (35 mg/kg i.p.) on enzyme activities related to energy transduction was investigated on the homogenate "in toto", non-synaptic mitochondrial fraction and synaptosomal fraction isolated from different rat brain areas (cerebral cortex, hippocampus, hypothalamus, striatum, and medulla oblongata). 6AN treatment decreased: phosphofructokinase in all the areas tested; lactate dehydrogenase on the homogenate "in toto" in striatum and hypothalamus, and on the synaptosomal fraction in cerebral cortex and corpus striatum; succinate dehydrogenase on non-synaptic mitochondrial fraction in hippocampus and striatum. Finally, aspartate aminotransferase was increased on non-synaptic mitochondrial fraction in striatum and medulla oblongata. Phenobarbital treatment induced an increase of total NADH cytochrome c reductase on mitochondrial fraction in hippocampus and hypothalamus, and a decrease of cytochrome oxidase activity on non-synaptic mitochondrial fraction in hypothalamus and medulla oblongata.

6-Aminonicotinamide↗
PubMed1987

Changes of synaptosomal energy metabolism induced by hypoxia during aging.

Synaptosomes were isolated from the motor area of the cerebral cortex of normoxic or hypoxic (PaO2 = 17-19 mmHg, for 15 min) beagle dogs of different ages. Synaptosomes were incubated in Krebs-Henseleit-Hepes buffer (for 10 min at 24 degrees C) and the energetic state was defined by: the balance of the labile phosphates (ATP, ADP, AMP, and creatine phosphate); the respiratory rate; the redox state of the intramitochondrial NAD-couple. By the present experimental model, it is possible to evaluate the potential damage (induced by the "in vivo" hypoxic insult) that synaptosomes cannot reverse under optimal incubation. Aging affected the phosphorylation state of the post-hypoxic incubated synaptosomes. The oxygen consumption rate was quite similar in the synaptosomal fractions from the motor area of hypoxic beagle dogs of different ages, but the cytochrome c and a contents were lower in the preparations from hypoxic older brains. In dogs of different ages, hypoxia always lowered the respiration of the synaptosomes, but aging affected the oxygen consumption rates only in post-hypoxic synaptosomes incubated with succinate. The synaptosomal energetic state was defined also by the redox state of the intramitochondrial NAD-couple (delta Gox-red) and the phosphorylation state of adenine nucleotide system (delta GATP). The free-energy change (delta delta G) for the coupled reactions was calculated, too. In synaptosomes isolated from the cerebral cortex of dogs submitted to hypoxia, the equilibrium (calculated for the mitochondrial electron transfer chain and the phosphorylation of adenine nucleotides) was markedly altered as function of aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1987

Energetic state of aged brain during hypoxia.

Synaptosomes isolated from the forebrain of rats of different ages (20, 60, 100 and 140 weeks of age) and incubated in Krebs-Henseleit-Hepes pH 7.4 buffer (for 10 min at 24 degrees C) were utilized to define the redox state of the intramitochondrial NAD couple (delta Gox-red) and the phosphorylation state of adenine nucleotide system (delta GATP). The free-energy change (delta delta G) for the coupled reactions was calculated. The animals were subjected for 10 min to different degrees of in vivo hypoxia (52 greater than or equal to PaO2 greater than or equal to 11 mm Hg). In synaptosomes isolated from the forebrain of animals submitted to moderate degrees of hypoxia, the trend of delta delta G was quite similar to that observed in normoxia. In synaptosomes isolated from the forebrain of rats submitted to severe degrees of hypoxia, the delta delta G was markedly altered as function of both aging and severity of hypoxemia. The extensive delta delta G changes were largely supported by alteration of the phosphorylation state of adenine nucleotides. However, in synaptosomes from severely hypoxic rats, aging affected the redox state, too.

Aging↗
PubMed1986

Brain enzyme adaptation to mild normobaric intermittent hypoxia.

The adaptation to repeated periods of intermittent normobaric hypoxia (oxygen:nitrogen = 10:90, 12 hr daily for 5 days) of some specific enzymatic activities related to energy metabolism has been observed in different rat brain areas (cerebral cortex, hippocampus, corpus striatum, hypothalamus, cerebellum, and medulla oblongata). The evaluation of the maximum rate (Vmax) of the enzymes was carried out on: the homogenate "in toto," the nonsynaptic mitochondrial fraction, and the crude synaptosomal fraction. The adaptation to intermittent normobaric hypoxic exposure was characterized by significant modifications of some enzyme activities in the homogenate "in toto" (decrease of hexokinase activity in cerebellum), in the nonsynaptic mitochondrial fraction (increase of succinate dehydrogenase activity in corpus striatum and decrease of cytochrome oxidase activity in cerebral cortex), and, particularly, in the synaptosomal fraction (decrease of cytochrome oxidase activity in cerebral cortex, hippocampus, corpus striatum, and cerebellum, and decrease of malate dehydrogenase and lactate dehydrogenase activity in cerebellum). The adaptation to normobaric intermittent hypoxia differs according to the brain area, subcellular fraction, and enzyme activity tested.

Adaptation, Physiological↗
PubMed1986

[Danazol: a new hormonal post-coital contraceptive method].

During a 9-month period, 84 female patients received post-coital contraception consisting either of an association of ethinyl estradiol/norgestrel or of danazol, in order to compare the safety and any adverse reaction of these 2 treatments. Overall, the patients treated with danazol presented 1/3 as many side effects. Nausea was reduced to 1/3 in frequency and vomiting to 1/9 in this group. 5 pregnancies were confirmed in the ethinyl estradiol/norgesterol group and 2 in the danazol group. Although more cases are needed, it would appear that danazol is characterized by greater efficacy and patient acceptability.

Biology↗
PubMed1986

Hopantenate interference on the adaptation of muscular energy metabolism to intermittent hypoxia.

In rat gastrocnemius muscle, the concentrations of glycolytic fuels, intermediates and end-products; Krebs cycle intermediates and related free amino acids; ammonia; energy store and mediators; and the energy charge potential were evaluated in normoxia or after repeated, alternate hypoxic and normoxic exposures (12 hr of hypoxia daily; for 5 days) with or without treatment with hopantenate (HOPA). Furthermore, in the crude extract and/or mitochondrial fraction the maximum rate (Vmax) of some muscular enzymes related to the anaerobic glycolytic pathway; the tricarboxylic acid cycle; and the electron transfer chain were evaluated. Hopantenate was administered daily at the dose of 250 mg.kg-1 i.p., for 5 days, 30 min before the beginning of the experimental normobaric hypoxia. The biochemical adaptation to intermittent normobaric hypoxic-normoxic exposures was characterized by the decrease of the muscular concentrations of citrate, alpha-ketoglutarate and glutamate, in absence of changes in the Vmax of the muscle enzymes related to energy transduction. In gastrocnemius muscle from hypoxic rats, by HOPA treatment, both citrate and alpha-ketoglutarate maintained normal values, aspartate decreased, while glutamate remained reduced to subnormal values. In the muscle from hypoxic animals, by hopantenate treatment the Vmax of the mitochondrial enzymes tested (citrate synthase, malate dehydrogenase, total NADH cytochrome c reductase, cytochrome oxidase) decreased in comparison with both hypoxic and normoxic untreated animals. This behaviour could be tentatively related to a mitochondrial sparing action concomitant with an intervention of the glutamate group of amino acids, even if the results do not allow a clear interpretation of the mechanism of HOPA action.

Animals↗
PubMed1986

Action of L-acetylcarnitine on different cerebral mitochondrial populations from hippocampus.

The maximal rate (Vmax) of some mitochondrial enzymatic activities related to the energy transduction (citrate synthase, malate dehydrogenase, NADH cytochrome c reductase as total, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase) were evaluated in non-synaptic (free) and synaptic mitochondria from rat brain hippocampus. Three types of mitochondria were isolated from rats subjected to single i.m. treatment with L-acetylcarnitine (308 mg X kg-1) or to sub-chronic i.m. treatment with L-acetylcarnitine at three different dose levels (38; 154; 614 mg X kg-1, 5 days a week, for 4 weeks). With respect to the enzymatic pattern of three types of non-synaptic and synaptic mitochondria, in hippocampus a different maximal rate of both total NADH-cytochrome c reductase and cytochrome oxidase was observed, these activities being lower in "synaptic heavy" mitochondrial subfraction rather than that in both "free" and "synaptic light" ones. This confirms that in various types of brain mitochondria a different metabolic machinery exists. Acute treatment with L-acetylcarnitine decreased citrate synthase and glutamate dehydrogenase activities only in mitochondria obtained from synaptosomes. The sub-chronic treatment with L-acetylcarnitine decreased the activity of citrate synthase and total NADH-cytochrome c reductase activities only in the same type of mitochondria, i.e. synaptic mitochondria. Therefore in vivo administration of L-acetylcarnitine mainly affects some specific enzyme activities (suggesting a specific molecular trigger mode of action) of the intrasynaptic mitochondria (suggesting a specific subcellular trigger site of action).

Acetylcarnitine↗
PubMed1985

Influence of aging and exogenous substances on cerebral energy metabolism in posthypoglycemic recovery.

In rats of different ages, acute severe hypoglycemia with isoelectric EEG induced extensive deterioration of the energy state and gross alteration of amino acid contents. During recovery of adult animals, tissue glucose concentration returned to normal, while the rate of glycogen synthesis was slow, both lactate and pyruvate concentrations increasing above normal. In the recovery period of "adult" rats, the ATP concentration increased but the adenine nucleotide pool remained reduced, even if the ADP and AMP concentrations were close to normal. Phosphocreatine was restored to normal concentrations with reciprocal changes in creatine content. In adult rats, during the recovery there was a rise in glutamate and glutamine concentrations, gamma-aminobutyrate concentration returning to normal value. Ammonia and aspartate decreased below normal, while alanine increased above normal. Aging does not affect the cerebral metabolic derangement occurring in severe hypoglycemia, but rather the metabolic changes that the brain tends to reverse during the posthypoglycemic restitution. In fact, there was lower restitution of the concentrations of cerebral cortical metabolites of "mature" and "senescent" rats in comparison with "adult" ones. Particularly, in older brains the concentrations of many amino acids and adenylate nucleotides remained largely abnormal. The effect of some agents on the posthypoglycemic recovery was tested: (a) dihydroergocristine; (b) eburnamonine; (c) raubasine; (d) almitrine; (e) piracetam. During the posthypoglycemic recovery, these different agents exhibited different interferences on glycolytic metabolites, amino acids and energy-rich phosphates. However, a more limited effect of the tested agents, which decrease with aging, was observed.

Aging↗
PubMed1985

Free mitochondria and synaptosomes from single rat forebrain. A comparison between two known subfractionation techniques.

Two published subcellular subfractionation techniques employing Ficoll-sucrose or sucrose-density gradient centrifugation, respectively, are evaluated for their capacity to yield fractions containing free mitochondria and synaptosomes from a single rat forebrain. The enzymes lactate dehydrogenase, acetylcholinesterase, NAD(P)H-cytochrome c reductase, and citrate synthase, markers of different subcellular components, were used to assess the purity and integrity of the fractions. Judged by the distribution of these specific enzymatic markers, the free mitochondria obtained by the Ficoll-sucrose gradient technique were less contaminated by synaptosomes and had greater biochemical integrity than those obtained by the sucrose-gradient technique. By contrast, the synaptosomes obtained by the Ficoll-sucrose gradient technique resulted in more contamination by microsomes than those prepared in a sucrose gradient.

Acetylcholinesterase↗