Effect of some drugs on cerebral energy state during and after hypoxia and complete or incomplete ischemia.
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Animals↗
Biomedical subjects
O Pastoris
Publications and source records attributed to O Pastoris.
In vitro action of uridine diphosphate glucose (UDPG) on phrenic diaphragm preparations.
The action of uridine-5'-diphosphoglucose (UDPG) on the contractile response of the phrenic diaphragm preparation from guinea pig was investigated. UDPG activity was assayed on the preparation at rest or during the exercise; in this case indirect electrical stimulation of phrenic diaphragm preparation or direct stimulation of denervated or curarized muscle were employed. Krebs' solutions adequately modified with regard to glucose concentration were used. The effect of UDPG on the neuromuscular junction was also investigated by recording miniature end plate potentials. An effect of the drug on neuromuscular transmission and on glucose metabolism could be demonstrated.
Action Potentials↗
Cerebral energy state during or after hypoxia and complete or incomplete ischemia.
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Animals↗
Drug action on cerebral energy state during and after various hypoxic conditions.
The behaviour of fuels (glycogen, glucose), of glycolytic pathway intermediates (glucose-6-phosphate, pyruvate) and end-product (lactate), as well as the pool of labile phosphates (ATP, ADP, AMP, creatine phosphate) and the energy charge of the brain were studied in the motor area of the cerebral cortex of beagle dogs. These parameters were evaluated both after various hypoxic conditions (hypoxic hypoxia, hypoxia plus complete or incomplete ischemia) and after 3, 15 or 30 min of post-hypoxic recovery and recirculation. The effect of some drugs (papaverine, UDP-glucose, (-)eburnamonine, suloctidil) following intracarotid perfusion has been evaluated in the various quoted experimental conditions. The tested drugs proved unable to improve the deranged brain metabolism under all the hypoxic conditions. On the contrary, an activating effect of suloctidil and (-)eburnamonine could be observed during the recovery after both hypoxia and hypoxia plus complete ischemia, papaverine being ineffective and UDP-glucose increasing the glycogen synthesis. The drugs proved unable to induce a restitution of the altered brain metabolism after hypoxia plus incomplete ischemia.
Adenosine Triphosphate↗
Metabolism and cerebral energy state: effect of acute hyperammonemia in beagle dog.
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Aerobiosis↗
Influence of training and pharmacological treatment on muscular enzymatic activities.
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Animals↗
Drugs and brain mitochondrial enzymatic activities during post-natal development in rat.
The enzymatic activities of two mitochondrial enzymes, i.e. succinate dehydrogenase and NADH-cytochrome c reductase were investigated in the brain of rats at different stages of post-natal development. In addition, the effect of the pharmacological treatment with two drugs, nicergoline and bamethan, able to interact with the alpha or the beta receptors respectively, was evaluated. The results show that both the enzymatic activities rapidly increase in the first days of extra-uterine life, thus indicating an adaptation of mitochondrial oxidative processes to post-natal environmental conditions. The pharmacological treatment with the two drugs does not induce any changes in the enzymatic activities tested.
Animals↗
Muscle metabolism investigated at rest and during exercise and/or pharmacological treatment by vasodilators.
The Ruderman's preparation was utilized to investigate in situ some aspects of the muscular metabolism both at rest and during submaximal exercise upon bilateral sciatic nerve stimulation, and/or during perfusion with some vasodilators: papaverine, caffeine, nicergoline, bamethan. O2 and glucose uptake, the production of lactate and the glycogen level of the muscle were studied. The availability of acetoacetate modifies the muscular metabolism; other fuels (e.g. the ketone body itself) are probably used for energetic purposes both under basal conditions and during exercise, even in the presence of high glycogen concentrations in the tissues. Some vasodilators increase the utilization of other fuels in replacement of glycogen (e.g. nicergoline), some others increase the ulilization of glycogen itself (e.g. bamethan and caffeine), whereas others (e.g. papaverine) do not effect the biochemical parameters studied. The present data confirm the importance both of the substrate availability and of the power of drugs to interfere with some enzymatic systems which modulate the utilization of available substrates, especially during exercise.
Animals↗
Modifications in cerebral lipid metabolism by severe glucose deprivation during aging.
Severe glucose deprivation causes extensive derangement of phospholipids, fatty acids and free fatty acids in cerebral cortex of rats of different ages. The hypoglycemia-induced cerebral loss of phospholipids and fatty acids persists after 60 min recovery. Changes in individual classes of lipids are largely affected by aging. In fact, during glucose deprivation and recovery, in adult animals no preferential loss of polyunsaturated fatty acids and ethanolamine phosphoglycerides occurs, suggesting that the loss could be related to oxidative rather than to peroxidative degradation. On the contrary, in senescent rats the quoted events occur, suggesting the hypothesis of a possible peroxidation of cerebral lipids. Pretreatment with some agents is performed to elucidate the aging mode of action. Papaverine (acting on macrocirculation) is uneffective, while raubasine (acting on microcirculation and metabolism) and almitrine (acting on oxygen availability) interfere with the phospholipid and fatty acid metabolism, their action being different according to the rat age.
Aging↗
Influence of aging on the acute depletion of reduced glutathione induced by electrophilic agents.
A severe age-dependent depletion of reduced glutathione (GSH) occurs in rat forebrain at 1-3 h from intraperitoneal injection of the electrophilic agents cyclohexene-1-one and cycloheptene-1-one. Chronic pretreatment with central dopamine agonists (i.e., ergot alkaloids; particularly, dihydroergocriptine) partially counteracts the GSH depletion induced in 15-month-old forebrains by the prooxidants tested. In contrast, chronic pretreatment with a vasodilator agent (i.e., papaverine) magnifies the GSH depletion.
Aging↗
The mitochondrial electron transfer alteration as a factor involved in the brain aging.
The tissutal concentrations of reduced glutathione (GSH) and the contents of some key components in the electron transfer chain (namely ubiquinone, cytochromes b, c1, c, and aa3) of the intraterminal mitochondria are measured in the forebrains from 20-, 60-, or 100-week-old Wistar rats. Moreover, in 60-week-old rats, the biochemical analyses are performed also 18 h after the induction of a peroxidative stress by cyclohexene-1-one. The rats have been i.p. pretreated for 8 weeks (7 days/week) with agents acting on macrocirculation (papaverine), carbohydrate metabolism (hopanthenate), lipid metabolism (phosphatidylcholine), energy transduction (theniloxazine), and dopaminergic system (dihydroergocriptine). Brain aging is characterized by the decrease in both GSH and mitochondrial cytochrome aa3, without changes in ubiquinone and cytochrome b populations. In the same way, the peroxidative stress induced by cyclohexene-1-one causes both a GSH depletion and an imbalance among the concentrations of the mitochondrial electron transfer carriers. Only cytochrome aa3 retains all the partially-reduced oxygen intermediates tightly bound to its active sites. Therefore, it is possible to hypothesize that an electron leakage at the level of the auto-oxidizing chain components (i.e., cytochrome b and ubiquinone populations) increases the release of activated oxygen species (superoxide radical, hydroxyl radical). The treatment with the quoted pharmacological tools suggests that GSH and mitochondrial electron transfer carriers are functionally linked, but not interdependent one another.
Aging↗
Age-related alterations of skeletal muscle metabolism by intermittent hypoxia and TRH-analogue treatment.
The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- and 24-month-old rats in normoxia or subjected to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or the TRH-analogue posatireline was performed. The muscular concentration of the following metabolites related to the energy metabolism was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate; energy charge potential. Furthermore the maximum rate of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The age-related decrease in muscular glucose 6-phosphate, pyruvate and alanine concentrations and increase in citrate concentration were consistent with the age-related decreased hexokinase and increased citrate synthase activities. Ageing was characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential were unchanged. The chronic (4 weeks) intermittent normobaric mild and severe hypoxia-induced alterations of the components in the anaerobic glycolytic pathway, tricarboxylic acid cycle and energy storage, that were magnified in the skeletal muscle from the oldest animals. The effect of the chronic treatment with the TRH-analogue posatireline suggests that the action of central nervous system-acting drugs could also be related to their direct influence on the muscular biochemical mechanisms related to the energy transduction.
Aging↗
Influence of aging and drug treatment on the cerebral glutathione system.
Age-related changes of the components of the glutathione system (reduced and oxidized glutathione) were evaluated in forebrains from male Wistar rats aged 5, 10, 15, 20, 25, 30 and 35 months. The trend of both forms of glutathione and the glutathione redox index markedly differs with age. Reduced glutathione increases during the first third of a rat's life and decreases thereafter. In contrast, oxidized glutathione remains relatively constant during the first half of the life-span and increases thereafter. Thus, the glutathione redox index steadily declines with age after an increase during the first third of the rat's life-span. In rats aged 10, 20 or 30 months, chronic IP treatment for two months with drugs known to modify cerebral circulation (papaverine) or the cerebral metabolism (ergot alkaloids dihydroergocristine, dihydroergocriptine) indicates that, according to the age, the cerebral glutathione system may be modified by metabolic changes rather than by circulatory events.
Aging↗
Effect of hypoxia, aging and pharmacological treatment on muscular metabolites and enzyme activities.
The effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adult and mature beagle dogs. Furthermore, the possible interference of pharmacological treatment with nicergoline was evaluated in these conditions. Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose 6-phosphate, pyruvate, lactate), Kreb's cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate) and related free amino acids (glutamate, alanine), ammonium ion, energy store and mediators (ATP, ADP, AMP and creatine phosphate), and the energy charge potential were evaluated. Furthermore, in the crude extract and/or mitochondrial fraction of another portion of the same gastrocnemius muscle the maximum rate (Vmax) of some muscular enzymes related to the anaerobic glycolytic pathway (hexokinase, lactate dehydrogenase), the Kreb's cycle (citrate synthase, malate dehydrogenase), the aminoacid pool related to the Krebs' cycle (glutamate dehydrogenase and aspartate aminotransferase), the electron transfer chain (cytochrome oxidase) and NAD+/NADH exchanges (total NADH cytochrome c reductase) was evaluated. Some glycolytic metabolites and Krebs' cycle intermediates were modified by acute hypoxia, while free amino acids and energy mediators remained practically unchanged. The pharmacological treatment maintained the glucose and succinate muscular concentrations within the normal range, during hypoxia. The behaviour of muscular metabolites during hypoxia and/or post-hypoxic recovery is an age-related event. In fact, only in young-adult animals did the altered values return to normal in post-hypoxic recovery. In the present experimental conditions, only minor changes were observed as far as muscular enzyme activities are concerned. In any case, some enzyme activities tested showed different Vmax in young-adult dogs in comparison with mature ones.
Aging↗
[The influence of aging on cerebral energy metabolism following post-hypoglycemic recovery in the rat. Pharmacologic application].
Influence of aging on cerebral energetic metabolism was evaluated during and after severe hypoglycemia in rats respectively 20 (adults), 60 (matures) or 100 (senescents) week-old. Cerebral content of carbohydrates, amino-acids, ammonia, ATP, ADP, AMP, creatine phosphate and creatine was analysed after 20 min insulin induced hypoglycemia and after 20 min hypoglycemic recovery induced by glucose infusion. In the rats of different ages tested, effect of raubasine (0.85 mg X kg-1 i.p. and i.v.), almitrine (2.68 mg X kg-1 i.p. and i.v.) and association almitrine plus raubasine (at the same doses) on post-hypoglycemic recovery was tested. Aging does not affect the cerebral metabolic disorders occurring in severe hypoglycemia, but rather the metabolic changes during the post-hypoglycemic restitution. In fact there is lower restitution of the concentrations of cerebral cortical metabolites in older rats: the concentrations of many amino-acids and adenylate nucleotides remains largely abnormal. Compared with saline treated post-hypoglycemic rats, raubasine decreases by 15 to 20% cerebral glucose and pyruvate contents in "adults" and "matures" rats and by 10 to 15% glutamate content in rat of different ages tested. Almitrine decreases by 20% cerebral glucose concentration in "matures" and "senescent" rats. In this latter group, almitrine decreases lactate and ammonium contents and increases by 23% glutamine level. In rats of all ages that were submitted to 20 min insulin induced hypoglycemia followed by 20 min glucose induced post-hypoglycemic recovery, the association almitrine plus raubasine decreases by 20 to 30% cerebral glucose, pyruvate and lactate contents and decreases by 15% glutamate. In older brains the association almitrine plus raubasine decreases by 50% cerebral content in ammonium and concomitantly induces an equivalent increase in glutamine content. The effect of the combination almitrine plus raubasine is characterized by an increase in rate of metabolic recovery process in all ages tested.
Aging↗
Instrumental and metabolic evaluation of patients affected by peripheral arterial occlusive disease (PAOD) following surgical revascularization surgery.
Experiments were performed on eight subjects affected by peripheral arterial occlusive disease (PAOD) of the lower limbs. Each patient was submitted to Ecodoppler, angiography and the "Treadmill test". Two bioptic muscle of these patients. A sample was used for the spectrophotometric and spectrophotofluorimetric determinations of: glycogen, pyruvate, lactate, citrate, alpha-ketoglutarate, malate, aspartate, glutamate, AMP, ADP, ATP and creatine phosphate (CP). The other bioptic sample was used to determine the following enzyme activities: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, total NADH cytochrome c reductase, cytochrome oxidase, aspartate aminotransferase and alanine aminotransferase. Patients showed an increase in lactate dehydrogenase, total NADH cytochrome c reductase and succinate dehydrogenase activities, a decrease in glycogen, ATP and CP concentrations. Telethermographic data showed patient muscle thermic emission quantitatively different from control group. The telethermographic test can be used as an additional diagnostic tool to determine and monitor the efficiency of a muscle undergoing metabolic failure.
Adult↗