ubiquinone and Cerebrovascular-Disorders

Topics: Alzheimer Disease; Animals; Antioxidants; Benzoquinones; Cerebrovascular Disorders; Friedreich Ataxia; Humans; Liver Diseases; Ubiquinone

Topics: Aged; Antidepressive Agents; Benzoquinones; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Dementia; Humans; Middle Aged; Morpholines; Ubiquinone; Vasodilator Agents

Chronic cerebral hypoperfusion (CCH) might account for the cognitive deficits associated with vascular cognitive impairment, but the mechanisms of hypoperfusion insulting to the cognition remain obscure. In the present study, Wistar rats underwent permanent occlusion of bilateral common carotid arteries to induce CCH. 2D-DIGE combined with MALDI-TOF MS was applied to determine the proteins that were differentially expressed in synaptosomes of prefrontal cortex and hippocampus. ATPsynβ, NDUFS1, UQCRC1 and Hsp70 were elevated both in synaptosomes of cortex and hippocampus at week 2 after operation, but subsided to baseline at week 4 except ATPsynβ which was still upregulated in synaptosomes of hippocampus at week 4. IDH3A and PDC-E2 were increased, respectively, in synaptosomes of prefrontal cortex and hippocampus at week 2, and showed no difference when compared to control at week 4. Malate dehydrogenase showed no difference in synaptosomes of prefrontal cortex and hippocampus at week 2, but showed an elevation in synaptosomes of prefrontal cortex at week 4. Our results imply that metabolic reserve and anti-oxidative stress might transiently exist in the early stage of CCH, which probably help cognitive save.

Topics: Analysis of Variance; Animals; Brain; Cerebrovascular Disorders; Chronic Disease; Cognition Disorders; Disease Models, Animal; Electron Transport Chain Complex Proteins; Electrophoresis, Gel, Two-Dimensional; HSP70 Heat-Shock Proteins; Malate Dehydrogenase; Male; Mitochondrial Proton-Translocating ATPases; NADH Dehydrogenase; Rats; Rats, Wistar; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Synaptosomes; Ubiquinone

Cerebral ischemia followed by oxygen reperfusion induces apoptosis in hippocampal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). The overproduction of oxygen-free radicals that occurs in the tissues of SHRSP is implicated in reoxygenation injury after hypoxia. Antioxidants inhibit reoxygenation injury in hippocampal slices, and temporal cortices in Alzheimer's disease increase sensitivity to oxygen-free radicals. Because this sensitivity may contribute to the development of the disease, we have studied hypoxia and oxygen reperfusion using cortical neurons isolated from WKY and SHRSP (at 15 days of gestation). We have tried to determine whether cortical neurons are damaged under these conditions, and whether neurons from SHRSP are more vulnerable than those from WKY. We have tried also to verify whether neuronal damage is minimized by vitamin E using the following techniques: (a) Trypan blue staining, (b) in situ staining of apoptosis, (c) ultrastructural examination, and (d) measurement of lactic dehydrogenase (LDH) activity in the bathing medium. Furthermore, we have examined the mechanisms involved in the development of neuronal damage and have studied ways of minimizing it. We demonstrated that 36 hours of hypoxia significantly increased the rate of cell death in SHRSP (p < 0.01), although 12 to 24 hours of hypoxia did not increase cell death in either WKY or SHRSP. In addition, 6 to 36 hours of hypoxia and 1.5 to 5 hours of oxygen reperfusion heavily damaged cells of both WKY and SHRSP, and most became apoptotic or necrotic. In contrast, cells incubated with 50 to 300 microg/ml of vitamin E remained intact, although 10 to 20 microg/ml of vitamin E did not totally preserve the cells. Moreover, vitamin E protected the neurons from high concentrations of sodium nitroprusside (nitric oxide donor) in a dose-dependent manner. Vitamin E, when added to the cells, increased in concentration in a time-dependent manner over a 24-hour period and in a dose-dependent manner below 200 microg/ml, and it was detected mostly in the mitochondria. We also demonstrated that serial treatments with allopurinol (a xanthine oxidase inhibitor) or superoxide dismutase preserved neurons during hypoxia and oxygen reperfusion. These data indicate that SHRSP neurons are weaker than WKY neurons in long-term hypoxia; oxygen radical generation occurs in the early minutes after reperfusion, and then the oxygen-free radicals cause hea

Topics: Animals; Antioxidants; Apoptosis; Benzoquinones; Cerebral Cortex; Cerebrovascular Disorders; Free Radical Scavengers; Genetic Predisposition to Disease; Hypoxia, Brain; Necrosis; Neurons; Nitric Oxide; Osmolar Concentration; Oxygen; Rats; Rats, Inbred SHR; Rats, Wistar; Reperfusion; Superoxide Dismutase; Ubiquinone; Vitamin E

We investigated the effects of the combination of idebenone, an energy metabolism enhancer, and manidipine 2HCl, a dihydropyridine-derivative calcium antagonist, on neurological deficits and histological changes in the brain and kidneys of stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions (stroke). The SHRSP were kept on a 1% NaCl solution as their drinking water to synchronize the onset of stroke. After the onset of stroke symptoms, the salt solution was replaced with tap water. On the day following the onset of stroke, idebenone (50 mg/kg), manidipine 2HCl (2 mg/kg) or a combination of idebenone (50 mg/kg) and manidipine 2HCl (2 mg/kg) was administered orally once a day for 3 weeks. In the combination group and manidipine 2HCl-treated group, the neurological deficits after the onset of stroke were ameliorated during the entire experimentalperiod. Especially, the combination significantly decreased the number of days with severe neurological deficits as compared to the control group. The combination and manidipine 2HCl significantly recovered the decrease in body weight and ameliorated the increase of brain weight, which was mainly caused by edema, significantly as compared to the control group. Manidipine 2HCl ameliorated the histological changes in the brain. In the combination group, the histological changes in both the brain and the kidneys were ameliorated. In conclusion, the combination of idebenone and manidipine 2HCl significantly ameliorated the neurological deficits and the histological changes in the brain and the kidney of SHRSP with stroke as compared to each individual treatment. We concluded that manidipine 2HCl enhances the therapeutic effect of idebenone in the treatment of cerebrovascular diseases.

Topics: Administration, Oral; Animals; Benzoquinones; Brain; Calcium Channel Blockers; Cerebrovascular Disorders; Dihydropyridines; Drug Combinations; Drug Synergism; Drug Therapy, Combination; Kidney; Male; Nitrobenzenes; Piperazines; Rats; Rats, Inbred SHR; Ubiquinone

The effect of oxiracetam (CGP 21690E, CAS 62613-82-5) on cerebrovascular impairment was investigated in rats. 1. After injection of tranylcypromine (a MAO inhibitor), spontaneously hypertensive rats (SHR) which had been previously infused with norepinephrine (NE) for 14 days displayed stroke-related behaviour including kangaroo-like posture, seizures and death. Administration of oxiracetam at doses of 400 and 800 mg/kg/d p.o. for 14 days before tranylcypromine injection inhibited the stroke-related behaviour. 2. Bilateral common carotid and vertebral artery occlusion induced electroencephalogram (EEG) flattening, the EEG recovering gradually after re-perfusion of cerebral blood flow. Oxiracetam administered after the re-perfusion at a dose of 100 mg/kg, i.v. accelerated the recovery. This facilitatory effect was not seen when either piracetam (50 and 100 mg/kg i.v.) or idebenone (50 and 100 mg/kg i.v.) were administered. 3. Occlusion of middle cerebral artery produced cerebral infarction and disturbed the circadian rhythm of spontaneous motor activity with an relative increase of activity in the light period. Treatment with oxiracetam (400 mg/kg/d p.o.) for 14 days after the occlusion showed a tendency to an improvement in the disturbed circadian rhythm but did not influence the size of brain infarction. From these results, oxiracetam is thought to have a protective effect in cerebrovascular impairment.

Topics: Animals; Behavior, Animal; Benzoquinones; Blood Pressure; Cerebral Arteries; Cerebral Infarction; Cerebrovascular Disorders; Electroencephalography; Male; Motor Activity; Norepinephrine; Piracetam; Pyrrolidines; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Tranylcypromine; Ubiquinone

Many CoQ trials for mitochondrial encephalomyopathy are reported, however, the action of CoQ in the central nervous system is unknown. We administered CoQ to a patient with MELAS, and decreasing CSF lactate and pyruvate levels were revealed. This reduction in CSF lactate and pyruvate may be evidence that CoQ acts directly on the CNS. There have been no other descriptions of evidence of CoQ effective action in the central nervous system, a finding unique to this report.

Topics: Acidosis, Lactic; Adult; Agnosia; Cerebrovascular Disorders; Delirium; Dose-Response Relationship, Drug; Hemianopsia; Humans; Lactates; Lactic Acid; Magnetic Resonance Imaging; Male; Mitochondria, Muscle; Neurologic Examination; Neuromuscular Diseases; Pyruvates; Pyruvic Acid; Syndrome; Ubiquinone

Two patients with mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS) in one family are reported. Pathological examination of case 1 showed ragged-red fibers, with 7% of the fibers being unstained by cytochrome c oxidase stain, peripheral nerve damage, multiple areas of softening in the cerebrum and midbrain, and spongy changes in the cerebrum, optic nerve and pons. Electron microscopic examination revealed abnormal accumulations of mitochondria in the skeletal muscle, smooth muscle and cardiac muscle. The activity of cytochrome c oxidase in the brain and liver showed a tendency to decrease. In case 2 (maternal aunt of case 1), muscular weakness and peripheral nerve damage improved by treatment with coenzyme Q10. By adding idebenone to the coenzyme Q10 therapy, the EEG and Wechsler's Adult Intelligence Scale (WAIS) improved. Furthermore, in the cerebral spinal fluid (CSF), the protein, lactate, and pyruvate decreased, and the monoamines and monoamine metabolites increased.

Topics: Acidosis, Lactic; Adolescent; Benzoquinones; Brain Diseases; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Mitochondria, Muscle; Quinones; Syndrome; Ubiquinone

The effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone) on neurological deficits following cerebrovascular lesions were examined in stroke-prone spontaneously hypertensive rats (SHRSP). The SHRSP were maintained on a 1% NaCl solution as drinking water to shorten the onset time of cerebrovascular lesions (stroke). After the onset of stroke, the salt solution was exchanged for tap water, and idebenone (30 and 100 mg/kg) was administered orally once daily for 3 weeks. The neurological deficits were evaluated by a specially designed scoring system or by an open-field test. Idebenone decreased the severity of the neurological deficits in a dose-dependent manner and this was statistically significant in the high-dose group. The severity of neurological changes was inversely related to the motor activity in the open-field test performed when the experiment was terminated, indicating the appropriateness of the scoring system. Moreover, the compound (100 mg/kg) significantly ameliorated a decrease in food intake (anorexia) that followed the onset of stroke. These results suggest that idebenone may be useful to treat patients with cerebrovascular lesions.

Topics: Animals; Benzoquinones; Body Weight; Brain; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Eating; Male; Motor Activity; Quinones; Rats; Rats, Inbred SHR; Ubiquinone

The effects of idebenone, a cerebral metabolic enhancer, on learning and memory impairment in two rat models with central cholinergic or serotonergic dysfunction were investigated using positively reinforced learning tasks. A delayed alternation task using a T maze was employed to test the effect of idebenone on short-term memory impairment induced by a cholinergic antagonist, scopolamine. A correct response, defined as a turn toward the arm opposite to that in the forced run, was rewarded with food pellets. Scopolamine (0.2 and 0.5 mg/kg, i.p.) significantly decreased the correct responses to the chance level in the 60-s-delayed alternation task. The scopolamine (0.2 mg/kg, i.p.)-induced impairment of short-term memory was improved by idebenone (3-30 mg/kg, i.p.) or an acetylcholinesterase inhibitor, physostigmine (0.1 and 0.2 mg/kg, i.p.), administered simultaneously. The central serotonergic dysfunction model was produced by giving rats a diet deficient in tryptophan, a precursor of serotonin. The rats fed on a tryptophan-deficient diet (TDD) showed a slower learning process in the operant brightness discrimination task (mult V115 EXT) than did rats fed on a normal diet. Idebenone (60 mg/kg/day) admixed with the TDD decreased the number of lever-pressing responses emitted during the extinction periods. The percentage of correct responses was significantly higher in the idebenone-treated group than in the control TDD group. These results suggest that idebenone may improve both the impairment of short-term memory induced by a decreased cholinergic activity and the retardation of discrimination learning induced by central serotonergic dysfunction.

Topics: Acetylcholine; Animals; Benzoquinones; Cerebral Cortex; Cerebrovascular Disorders; Discrimination Learning; Learning Disabilities; Male; Memory Disorders; Memory, Short-Term; Quinones; Rats; Rats, Inbred Strains; Scopolamine; Serotonin; Ubiquinone

Two rat models of memory impairment in passive avoidance learning induced by cerebrovascular disturbance, were established to estimate the effects of a cerebral metabolic enhancer, idebenone. Transient and global cerebral ischemia in rats, produced by 4-vessel occlusion for 200 s immediately after the acquisition trial of passive avoidance learning, shortened the latencies in the retention test trial performed 24 h later. This retrograde amnesia was reversed significantly by idebenone administered orally or intraperitoneally at the doses of 10 and 30 mg/kg before the retention test trial. Idebenone at a dose of 10 mg/kg, given intraperitoneally before or immediately after the ischemia, also markedly inhibited the appearance of amnesia. In the second model, permanent and cerebral hemisphere embolization produced by injecting 2,000 microspheres into the internal carotid artery, significantly impaired passive avoidance learning performed 7 days later. The repeated administration of idebenone (30 mg/kg, i.p.). once a day after the embolization, significantly improved the impairment of passive avoidance learning in the embolized rats. Furthermore, physostigmine and arginine-vasopressin as reference compounds improved the impairment of passive avoidance learning in these models. These findings suggest that idebenone ameliorates memory impairment induced by cerebral vascular disturbance in rats.

Topics: Administration, Oral; Animals; Avoidance Learning; Benzoquinones; Brain Ischemia; Cerebrovascular Disorders; Injections, Intraperitoneal; Intracranial Embolism and Thrombosis; Male; Memory Disorders; Quinones; Rats; Rats, Inbred Strains; Ubiquinone

To investigate the possible action sites of a cerebral metabolism activator, idebenone, (6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone), its distribution in the brain and effect on local cerebral glucose utilization (LCGU) were studied in normal (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions. 14C-Idebenone distributed rapidly into the brain after intravenous administration (10 mg/kg), and the total 14C contents in the brain at peak time corresponded to 0.45-0.56% of the dosages. An autoradiographic study showed that the 14C levels were higher in the white than in the gray matter. When 14C-idebenone was administered orally (100 mg/kg) and intraperitoneally (30 mg/kg), the total 14C levels were not markedly different among the brain regions of the rats. The concentration of unchanged idebenone was higher in the cerebral cortex, thalamus, and cerebellum than that in the other brain regions. Studies on LCGU demonstrated that idebenone (30 mg/kg/day, i.p., for 3 days) improved the reduction of LCGU in SHRSP with stroke, especially in the temporal cortex, thalamus dorsomedial nucleus, subthalamic nucleus, mamillary body, hippocampus dentate gyrus, caudate-putamen, inferior colliculus, and cerebellar nucleus. Based on these results, possible action sites of idebenone for its main pharmacologic effects are discussed.

Topics: Animals; Benzoquinones; Brain; Cerebrovascular Disorders; Glucose; Male; Quinones; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Ubiquinone

Stroke-prone spontaneously hypertensive rats (SHRSP) were kept on a 1% NaCl solution as drinking water to shorten the onset-time of a stroke. The level of lipoperoxide (LPO) in the erythrocytes of SHRSP loaded with salt for 22 days was significantly higher than that of the controls. Idebenone treatment (30 mg/kg per day, p.o.) markedly decreased the LPO to the level of the controls. Hemolysis in SHRSP was accelerated by the salt-loading. Idebenone significantly inhibited the hemolysis in a dose-dependent manner. These results suggest that idebenone inhibits lipid peroxidation in erythrocytes and stabilizes the erythrocyte membrane.

Topics: Animals; Benzoquinones; Cerebrovascular Disorders; Erythrocytes; Hemolysis; Hypertension; Lipid Peroxidation; Male; Quinones; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Ubiquinone

A daily dose of 90 mg of idebenone was given to nine patients with cerebrovascular disorders to investigate its effects on clinical symptoms and electroencephalograms (EEG). Changes in EEG before and after the administration were compared quantitatively by computer analysis using the wave-form recognition method. Significant increase in frequency in the alpha band (O1) and trends of increased appearance of beta waves, decreased appearance of alpha 1 bands, and lowered amplitude in the alpha 1 and alpha 2 bands were observed after administration of idebenone. The theta waves of 30 microV and over had a significantly diminished maximum amplitude (C3) and a tendency to appear less often. Mean frequency of the EEG and appearance of fast waves apparently increased in the patients showing improvement of the clinical symptoms as compared with those not showing improvement. The results suggested that idebenone improved the EEG in the patients with cerebrovascular disorders, causing changes in EEG similar to those observed with psychostimulants.

Topics: Adult; Aged; Aged, 80 and over; Benzoquinones; Cerebrovascular Disorders; Electroencephalography; Female; Humans; Male; Middle Aged; Quinones; Ubiquinone

A male with mitochondrial myopathy, encephalopathy, lactic acidemia, and strokelike episodes is reported. He had also recurrent episodes of ileus. Muscle biopsy revealed ragged-red fibres. The cytochemistry of cytochrome c oxidase (CCO) showed scattered nonstained fibres, while all muscle fibres were heavily stained by immunocytochemistry using CCO antibody. These findings suggest that partical CCO deficiency may be present in the skeletal muscles of the patient. NADH cytochrome c reductase in the patient's muscle mitochondria was low compared with normal controls (about 26%), although succinate cytochrome c reductase was normal. Coenzyme Q10 administration (90 mg/day) did not improve CSF lactate levels, but did decrease plasma lactate levels. His muscle weakness slightly improved.

Topics: Acidosis, Lactic; Adult; Brain Diseases; Cerebrovascular Disorders; Coenzymes; Electron Transport Complex IV; Humans; Intestinal Obstruction; Male; Mitochondria, Muscle; Muscular Diseases; Recurrence; Ubiquinone

Elucidation of the alterations of intracerebral neurotransmitters in cerebrovascular dementia is of prime importance not only in revealing patho-physiological mechanism but also in developing the therapy for the disease. We measured monoamine metabolites and norepinephrine (NE) in cerebrospinal fluid of patients with cerebrovascular dementia, to study the effects of administration of 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-metyl-1,4-benzoquinone (idebenone, CV-2619). Six patients with cerebral infarction and 1 with cerebral hemorrhage, at the mean age of 65.4 years, were enrolled as subjects. All patients had mental and intelligent impairment, and the Hasegawa's Dementia Rating (DR) Scale was performed. The patients were medicated with 90 mg daily dose of CV-2619 for 1 to 2 months, and homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylethylenglycol (MHPG), NE in cerebrospinal fluid were determined by high-performance liquid chromatography before and also after the medication. Before the medication, HVA was 21.7 +/- 1.4 ng/ml (mean +/- SE), which was significantly low (p less than 0.01), compared with controls at a similar age: 5-HIAA was 18.5 +/- 2.7 ng/ml, and MHPG, 9.5 +/- 0.7 ng/ml, both of which were not significantly low, but tended to be low, compared with the controls. NE was similar to the control value. With the administration of CV-2619, HVA measured 27.1 +/- 3.2 ng/ml, showing a tendency to increase; 5-HIAA was 26.7 +/- 2.3 ng/ml, and MHPG, 10.7 +/- 0.6 ng/ml, both of which increased significantly (p less than 0.05), compared with the respective premedication values.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Benzoquinones; Biogenic Amines; Cerebrovascular Disorders; Chromatography, High Pressure Liquid; Dementia; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Quinones; Ubiquinone

To investigate the possible action-sites of a cerebral metabolism activator, idebenone (CV-2619), its distribution in the brain and effect on local cerebral glucose utilization (LCGU) were studied both in normal rats (WKY) and in stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions. At 5 min after intravenous administration of [14C] CV-2619 (10 mg/kg), the distribution ratio in the brain was 0.45-0.56% of the dosage. Autoradiographic study showed that 14C levels were higher in the white matter than in the grey matter. When [14C] CV-2619 was administered orally (100 mg/kg) and intraperitoneally (30 mg/kg), 14C levels in eleven brain regions (15 min after administration) were 0.22-0.39 microgram/g (CV-2619 equivalent) and 1.11-1.30 micrograms/g, respectively, in WKY and 0.17-0.28 microgram/g and 1.66-1.87 microgram/g, respectively, in SHRSP. Total 14C levels were not markedly different among the brain regions of the rats. The analysis of unchanged CV-2619 and its metabolites revealed that unchanged CV-2619 in the cerebral cortex, thalamus and cerebellum was relatively higher than that in the other brain regions. Studies on LCGU demonstrated that CV-2619 (30 mg/kg/day, i.p., for 3 days) improved the decrement of LCGU in the temporal cortex, thalamus dorsomedial nucleus, subthalamic nucleus, mamillary body, hippocampus dentate gyrus, caudate-putamen, inferior colliculus and cerebellar nucleus of SHRSP with stroke. Based on these results, the possible action-sites of CV-2619 for its main pharmacological effects were discussed.

Topics: Administration, Oral; Animals; Benzoquinones; Brain; Cerebrovascular Disorders; Glucose; Injections, Intravenous; Male; Quinones; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Ubiquinone

Coenzyme Q10 (CoQ10) and the opiate antagonist naloxone were compared as to their effect on the survival of mongolian gerbils with unilateral carotid ligation-induced stroke. Without medication all of the stroke gerbils died within 28 hours, but with a subcutaneous implantation of a 10 mg pellet of naloxone, 20% of the gerbils lived for 4 weeks. When a 250 mg pellet of CoQ10 was implanted subcutaneously, a definite effect on survival was observed, with 45% of the stroke gerbils living for 4 weeks. Considering that the action mechanisms of CoQ10 and naloxone are different, the combined use of these drugs in the treatment of stroke needs to be investigated.

Topics: Animals; Cerebrovascular Disorders; Coenzymes; Electron Transport; Gerbillinae; Levallorphan; Naloxone; Time Factors; Ubiquinone

The effects of CV-2619 on the half-life and hemolysis of red blood cells (RBC) in stroke-prone spontaneously hypertensive rats (SHRSP) were examined. The half-life of RBC in SHRSP was shorter than that in control Wistar Kyoto rats (WKY) and was significantly prolonged in SHRSP kept on a diet containing 0.1% (w/w) of CV-2619 (calculated at 71.0 mg/kg/day): 11.7 +/- 0.4 days in untreated SHRSP (n = 11); 13.8 +/- 0.1 days in treated SHRSP (n = 5, P less than 0.01); and 14.8 +/- 0.5 days in WKY (n = 6). The hemolysis of RBC in salt-loaded SHRSP was accelerated compared with that in WKY. In SHRSP given CV-2619 (20 or 70 mg/kg/day, p.o.) for 2 weeks, the hemolysis was significantly inhibited; the percent hemolysis was 43.9 +/- 0.9% (n = 10) in the control, 39.5 +/- 0.9% (n = 9, P less than 0.01) in the group given 20 mg/kg CV-2619, and 37.1 +/- 0.8% (n = 9, P less than 0.001) in the group given 70 mg/kg CV-2619. These results suggest that the stabilizing effect of CV-2619 on the membrane of RBC is involved in its therapeutic effects in cerebral vascular disorders.

Topics: Animals; Benzoquinones; Cerebrovascular Disorders; Erythrocyte Aging; Half-Life; Hemolysis; Male; Quinones; Rats; Rats, Inbred SHR; Ubiquinone

The effects of a novel compound, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619), on cerebral and renal vascular changes were examined in stroke-prone spontaneously hypertensive rats (SHRSP) and in rats with experimentally induced hypertension. CV-2619 (35 mg/kg/day, p.o.) significantly inhibited the onset of cerebrovascular lesions (stroke) and the elevation of blood pressure in SHRSP with mild hypertension. A higher dose (2 X 50 mg/kg/day, p.o.) clearly delayed the onset of both stroke and proteinuria without any effect on the blood pressure in SHRSP with severe hypertension. In DOCA-salt hypertensive rats, CV-2619 (2 X 5 or 2 X 25 mg/kg/day, p.o.) dose-dependently inhibited decreases in body weight and water balance and the development of cerebral and renal vascular changes. These results suggest that CV-2619 inhibits the development of stroke and renal vascular lesions in hypertensive rats.

Topics: Animals; Benzoquinones; Blood Pressure; Body Weight; Brain; Cerebrovascular Disorders; Hypertension; Kidney; Male; Quinones; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors; Ubiquinone; Water-Electrolyte Balance