ubiquinone has been researched along with Brain-Ischemia* in 45 studies
1 review(s) available for ubiquinone and Brain-Ischemia
1 trial(s) available for ubiquinone and Brain-Ischemia
44 other study(ies) available for ubiquinone and Brain-Ischemia
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The neuroprotective effect of MicroRNA-149-5p and coenzymeQ10 by reducing levels of inflammatory cytokines and metalloproteinases following focal brain ischemia in rats.
The increase in some factors following cerebral ischemia, especially Matrix metalloproteinase (MMPs) and inflammatory factors lead to blood-brain barrier (BBB) damages, edema and neuronal death. Previous studies have shown that these molecules are miRNA-149-5p (miR-149) and Coenzyme (Co) Q10 targets. Therefore, in this study, the effect of mimic of miRNA-149-5p (mimic miR) and CoQ10 on the expression of metalloproteinase 1 and 2 and inflammatory cytokines following injury caused by cerebral ischemia is investigated. Cerebral ischemia was modeled by Middle Cerebral Artery Occlusion (MCAO). Male Wistar rats were randomly divided into 6 groups: sham (without surgery and treatment), control (MCAO), negative control (NC): MCAO + scrambled miR, vehicle: MCAO + Ethanole, first treatment: MCAO + mimic miR, second treatment: MCAO + Q10. Each group was divided into 6 subgroups to evaluate neurological defects, the volume of tissue damage using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, blood-brain barrier permeability using cerebral Evans Blue (EB) staining, edema by measuring the percentage of brain water, MMP-2,9 mRNA and miR-149-5p levels using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the levels of IL-6 and TNF-α proteins using ELISA. The data obtained from this study showed that the use of mimic miR and Q10 increased the level of miR-149, decreased the extent of neurological defects and tissue damage, increased BBB integrity, decreased brain water percentage and also decreased the level of inflammatory cytokines and MMPs. It seems that the use mimic of miRNA-149-5p and Q10 can have a protective effect on the brain by reducing MMPs and inflammatory factors following cerebral ischemia and this could lead to a new treatment strategy to reduce the complications of cerebral ischemia. Topics: Animals; Blood-Brain Barrier; Brain; Brain Edema; Brain Ischemia; Cytokines; Disease Models, Animal; Male; Metalloproteases; MicroRNAs; Neuroprotective Agents; Rats; Rats, Wistar; Ubiquinone | 2021 |
Neuroprotective potential of azilsartan against cerebral ischemic injury: Possible involvement of mitochondrial mechanisms.
Mitochondrial dysfunction is a major player in initiating the cellular cascades which lead to neuronal damage post cerebral ischemia. Angiotensin II Type 1 (AT1) receptor blockers are one of the most commonly employed antihypertensive drugs due to their good safety and efficacy profiles. This study was designed to investigate the neuroprotective potential of a newer AT1 receptor blocker azilsartan against global cerebral ischemia induced brain injury in Wistar rats and the possible involvement of mitochondrial restorative mechanism in its effect.. Bilateral common carotid artery occlusion (30min Ischemia and 48hr reperfusion) was performed in Wistar rats for the induction of global cerebral ischemia. Pre-treatment with azilsartan (2 and 4 mg/kg; p.o.) or coenzyme Q10 (20 and 40 mg/kg; p.o.) starting 7 days prior to BCCAO till the end of reperfusion was done.. Azilsartan and coenzyme Q10 preserved the behavioral function (locomotor activity, rota rod performance and beam balance score), arrested oxidative stress (LPO, nitrite, GSH and SOD), decreased apoptotic damage (caspase-3), neuroinflammation (TNF-α), infarct area (TTC staining) and restored histological alterations (H&E staining) as compared to vehicle treatment. Maximum effect was seen when a combination of both drugs was administered. In addition, azilsartan was able to protect the activity of mitochondrial complexes and in combination with the ubiquitous electron carrier coenzyme Q10, it significantly preserved the mitochondrial respiratory function by stimulating the oxidative phosphorylation (oxygen consumption using clarke's electrode).. These findings explicitly highlight neuroprotective properties of azilsartan against cerebral ischemia, possibly through mitochondrial mechanisms. Topics: Animals; Benzimidazoles; Brain Ischemia; Locomotion; Male; Mitochondria; Neuroprotective Agents; Oxadiazoles; Rats; Rats, Wistar; Ubiquinone | 2020 |
Effects of non-caloric ultrashort wave on the expression of CoQ10 and C1GALT1C1 in rats with cerebral ischemia reperfusion injury.
To examine the changes of coenzyme Q10 (CoQ10) and β. Fifty SD rats were randomly divided into 5 groups (. The infarct volume percentage after TTC staining was zero in the sham group. With the progress of disease and USW therapy, the infarct volume percentage was decreased in the experimental groups (all. Non-caloric USW therapy may upregulate the expression of CoQ10 to suppress the expression of C1GALT1C1 in rats, leading to alleviating cerebral ischemic reperfusion injury. Topics: Animals; Brain; Brain Ischemia; Molecular Chaperones; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ubiquinone | 2020 |
[Neuroprotective mechanisms of the ubiquinol action in experimental focal ischemia].
Ischemic stroke is one of the most socially important diseases characterized by impaired cerebral circulation with focal damage of the brain tissue and decreased functionality. Despite the successes of modern pharmacology, possibilities of pharmacotherapy for stroke remain limited, and the research for new drugs with neuroprotective effects that can prevent brain cell death is still relevant. In this study we have investigated the neuroprotective activity of ubiquinol as a part of an innovative form on a rat model of irreversible 24 h-cerebral ischemia with evaluation of the mechanisms of its neuroprotective effect. Ubiquinol (30 mg/kg), administered intravenously in the acute period of irreversible 24 h focal cerebral ischemia, had a direct neuroprotective effect, characterized by a decrease in the volume of brain tissue necrosis. The protective effect of ubiquinol is due to its ability to inhibit the development of oxidative stress by the direct anti-radical action, preventing the increase in the lipid hydroperoxide content in the brain tissue adjacent to the focus of necrosis, lowering the lipid oxidation rate in plasma against under conditions of increased total antioxidant activity in the brain and blood of experimental animals. In vitro experiments have shown the ability of ubiquinol to prevent cell death in primary culture of cerebral neurons of rat brain under 4 h oxygen/glucose deprivation followed by 20 h reoxygenation.. Ishemicheskiĭ insul't – odno iz naibolee sotsial'no-znachimykh zabolevaniĭ, kharakterizuiushchikhsia narusheniem mozgovogo krovoobrashcheniia s ochagovym povrezhdeniem tkani golovnogo mozga i narusheniem ego funktsiĭ. Nesmotria na uspekhi sovremennoĭ farmakologii, vozmozhnosti farmakoterapii insul'ta ostaiutsia ogranichennymi, i aktual'nym iavliaetsia poisk novykh lekarstvennykh preparatov neĭroprotektornogo deĭstviia, sposobnykh predotvratit' gibel' kletok golovnogo mozga. V dannoĭ rabote provedeno izuchenie neĭroprotektornoĭ aktivnosti ubikhinola v sostave innovatsionnoĭ formy na modeli neobratimoĭ 24 ch ishemii golovnogo mozga u krys s otsenkoĭ mekhanizmov ego neĭroprotektornogo deĭstviia. Pri vnutrivennom vvedenii v doze 30 mg/kg v ostrom periode 24 ch neobratimoĭ fokal'noĭ ishemii golovnogo mozga ubikhinol okazyval priamoe neĭroprotektornoe deĭstvie, kharakterizuiushcheesia umen'sheniem ob"ema ochaga nekroza tkani golovnogo mozga. Zashchitnyĭ éffekt ubikhinola obuslovlen sposobnost'iu prepiatstvovat' razvitiiu okislitel'nogo stressa za schet priamogo antiradikal'nogo deĭstviia putem predotvrashcheniia rosta lipidnykh gidroperekiseĭ v tkani mozga, prilezhashcheĭ k ochagu nekroza, snizheniia skorosti okisleniia lipidov v plazme krovi na fone povysheniia obshcheĭ antioksidantnoĭ aktivnosti kak v mozge, tak i krovi éksperimental'nykh zhivotnykh. V éksperimentakh in vitro pokazana sposobnost' ubikhinola predotvrashchat' gibel' neĭronov pervichnoĭ kul'tury kory bol'shikh polushariĭ golovnogo mozga krysy v usloviiakh 4 ch gliukozo-kislorodnoĭ deprivatsii s 20 ch reoksigenatsieĭ. Topics: Animals; Antioxidants; Brain Ischemia; Neurons; Neuroprotective Agents; Oxidative Stress; Primary Cell Culture; Rats; Ubiquinone | 2020 |
Idebenone attenuates cerebral inflammatory injury in ischemia and reperfusion via dampening NLRP3 inflammasome activity.
Idebenone is a well-appreciated mitochondrial protectant while the mechanisms underlying the neuroprotection in cerebral ischemia and reperfusion (I/R) remain elusive. It has been manifested NLRP3 inflammasom activation contributed to I/R induced damage. It raises questions how exactly NLRP3 inflammasom was activated in microglia and neuron and whether idebenone reverses the process in I/R.. I/R rat model was utilized and BV2, primary microglia and PC12 cells were subjected to oxygen-glucose deprivation (OGD). Then, western-blotting, q-PCR, immunofluorescence staining, ELISA, flow cytometry and immunoprecipitation analysis were performed.. We found ROS-NLRP3 singaling was activated in BV2 cells at OGD/R 24 h. Importantly, microglial NLRP3 activation was essential for NLRP3 activation in PC12 cells under microglial-neuronal co-culture circumstance, which has been confirmed to induced neuronal apoptosis. Further, we found mitochondrial dysfunction in OGD/R led to mt-DNA translocation as well as generation of mt-ROS, resulting cytosolic accumulation of oxidized mt-DNA. Ultimately, oxidized mt-DNA binding to NLRP3 contributed to further activation of NLRP3 and dramatically augmented inflammation in BV2 and PC12 cells. Furthermore, idebenone treatment inhibited the process, thus suppressing the NLRP3-mediated inflammatory injury after OGD/R. In vivo, NLRP3 was activated in microglia of I/R rats and inhibition of NLRP3 was observed in idebenone treatment group, which had less neurological deficit and less infarct volume.. Our data revealed the anti-inflammatory effects of idebenone via suppressing activation of NLRP3 and ameliorating NLRP3-mediating damage in I/R, which may provide new insight in therapeutic strategy for ischemic stroke. Topics: Animals; Animals, Newborn; Brain Ischemia; Cells, Cultured; Encephalitis; Inflammasomes; Male; Mice; Mice, Inbred C57BL; Neuroprotection; NLR Family, Pyrin Domain-Containing 3 Protein; PC12 Cells; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Stroke; Ubiquinone | 2020 |
Preventive Effects of Neuroprotective Agents in a Neonatal Rat of Photothrombotic Stroke Model.
Neonatal ischemic stroke has a higher incidence than childhood stroke. Seizures are the first sign for the need for clinical assessment in neonates, but many questions remain regarding treatments and follow-up modalities. In the absence of a known pathophysiological mechanism, only supportive care is currently provided. Stroke-induced microglia activation and neuroinflammation are believed to play a central role in the pathological progression of neonatal ischemic stroke. We induced a photothrombotic infarction with Rose Bengal in neonatal rats to investigate the effects of pre- and post-treatment with Aspirin (ASA), Clopidogrel (Clop), and Coenzyme Q10 (CoQ10), which are known for their neuroprotective effects in adult stroke. Pre-stroke medication ameliorates cerebral ischemic injury and reduces infarct volume by reducing microglia activation, cellular reactive oxygen species (ROS) production, and cytokine release. Post-stroke administration of ASA, Clop, and CoQ10 increased motor function and reduced the volume of infarction, and the statistical evidence was stronger than that seen in the pre-stroke treatment. In this study, we demonstrated that ASA, Clop, and CoQ10 treatment before and after the stroke reduced the scope of stroke lesions and increased behavioral activity. It suggests that ASA, Clop, and CoQ10 medication could significantly have neuroprotective effects in the neonates who have suffered strokes. Topics: Animals; Animals, Newborn; Aspirin; Brain Ischemia; Clopidogrel; Disease Models, Animal; Inflammation; Neuroprotective Agents; Rats; Rose Bengal; Stroke; Ubiquinone | 2020 |
Coenzyme Q10 supplementation improves acute outcomes of stroke in rats pretreated with atorvastatin.
Coenzyme Q10 (CoQ10, ubiquinone) stands among the safest supplements in the elderly to protect against cardiovascular disorders. Noteworthy, CoQ10 deficiency is common in many surviving stroke patients as they are mostly prescribed statins for the secondary prevention of stroke incidence lifelong. Accordingly, the current study aims to experimentally examine whether CoQ10 supplementation in animals receiving atorvastatin may affect acute stroke-induced injury.. Adult rats underwent transient middle cerebral artery occlusion after atorvastatin pretreatment (5 or 10 mg/ kg/day; po; 30 days) with or without CoQ10 (200 mg/kg/day). After 24 hours ischemic/reperfusion injury, animals were subjected to functional assessments followed by cerebral molecular and histological to detect inflammation, apoptosis and oxidative stress.. Animals dosed with 10 mg/kg presented the worst neurological function and brain damage in the acute phase of stroke injury. CoQ10 supplementation efficiently improved functional deficit and cerebral infarction in all stroke animals, particularly those exhibiting statin toxicity. Such benefits were associated with remarkable anti-inflammatory and anti-apoptotic effects, based on the analyzed tumor necrosis factor-α, interleukin-6, Bax/Bcl2 and cleaved caspase 3/9 immunoblots. Importantly, our fluoro-jade staining data indicated CoQ10 may revert the stroke-induced neurodegeneration. No parallel alteration was detected in stroke-induced oxidative stress as determined by malondialdehyde and 8-oxo-2'-deoxyguanosine levels.. These data suggest that all stroke animals may benefit from CoQ10 administration through modulating inflammatory and degenerative pathways. This study provides empirical evidence for potential advantages of CoQ10 supplementation in atorvastatin-receiving patients which may not shadow its antioxidant properties. Topics: Animals; Apoptosis; Atorvastatin; Brain Ischemia; Encephalitis; Male; Neuroprotective Agents; Oxidative Stress; Rats, Wistar; Stroke; Treatment Outcome; Ubiquinone | 2019 |
Effect of Coenzyme Q10 on Expression of UbiAd1 Gene in Rat Model of Local Cerebral Ischemia.
The study examined the effect of endogenous lipid-soluble antioxidant coenzyme Q10 on the expression of UbiA gene of prenyltransferase domain-containing protein 1 (UbiAd1) involved in synthesis of vitamin K2 (and probably of coenzyme Q10) on a rat model of ischemic stroke provoked by ligation of the middle cerebral artery in the left hemisphere. Ischemia enhanced expression of mRNA of UbiAd1 gene in both cerebral hemispheres, but the effect was significant only in the contralateral one. The study revealed no effect of intraperitoneal injection of coenzyme Q10 (30 mg/kg) on ischemia-produced elevation of mRNA of UbiAd1 gene. Further studies are needed to assess possible neuroprotective effects of antioxidant coenzyme Q10. Topics: Animals; Brain Ischemia; Cerebral Infarction; Dimethylallyltranstransferase; Male; Neuroprotective Agents; Rats; Ubiquinone | 2018 |
Coenzyme Q10 ameliorates cerebral ischemia reperfusion injury in hyperglycemic rats.
The purpose of this study is to investigate the effect of coenzyme Q10 (CoQ10) on focal cerebral ischemia/reperfusion (I/R) injury in hyperglycemic rats and the possible involved mechanisms. In this study, we established the transient middle cerebral artery occlusion (MCAO) for 30min in the rats with diabetic hyperglycemia. The neurological deficit score, 2,3,5-triphenyltetrazolium chloride (TTC) staining and pathohistology are applied to detect the extent of the damage. The expression of Fis1, Mfn2 and Lc3 in the brain is investigated by immunohistochemical and Western blotting techniques. The results showed that the streptozotocin-induced diabetic hyperglycemia and MCAO-induced focal cerebral ischemia were successfully prepared in rats. In the hyperglycemic group, the neurological deficit scores, infarct volumes, and number of pyknotic cells were higher than that in the normalglycemic group at 24h and/or 72h reperfusion. Pretreated with CoQ10 (10mg/kg) for four weeks could significantly reduce the neurological scores, infarct volume, and pyknotic cells at 24h and/or 72h reperfusion of the hyperglycemic rats compared with non-CoQ10 pretreated hyperglycemic animals. Immunohistochemistry and Western blotting showed that pretreatment with CoQ10 or insulin could significantly reduce the expression of Fis1 protein in the brain at 24h and 72h reperfusion. Inversely, a significantly increased expression of Mfn2 was observed in the rats CoQ10 or insulin pretreated at 24h and/or 72h reperfusion when compared with matched hyperglycemic rats. These results demonstrated that hyperglycemia could aggravate ischemic brain injury. Pretreatment with CoQ10 might ameliorate the diabetic hyperglycemia aggravated I/R brain damage in the MCAO rats by maintain the balance between mitochondrial fission and fusion. Topics: Animals; Brain; Brain Ischemia; Diabetes Mellitus, Experimental; Hyperglycemia; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ubiquinone | 2017 |
Intravenous Treatment With Coenzyme Q10 Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Brain Ischemia in Rats.
Coenzyme Q10 (CoQ10) crosses the blood-brain barrier when administered intravenously and accumulates in the brain. In this study, we investigated whether CoQ10 protects against ischemia-reperfusion injury by measuring neurological function and brain infarct volumes in a rat model of transient focal cerebral ischemia. In male Wistar rats, we performed transient middle cerebral artery occlusion (tMCAO) for 60 minutes, followed by reperfusion for 24 hours or 7 days. Forty-five minutes after the onset of occlusion (or 15 minutes before reperfusion), rats received a single intravenous injection of solubilized CoQ10 (30 mg·mL(-1)·kg(-1)) or saline (2 mL/kg). Sensory and motor function scores and body weights were obtained before the rats were killed by decapitation, and brain infarct volumes were calculated using tetrazolium chloride staining. CoQ10 brain levels were measured by high-performance liquid chromatography with electrochemical detection. CoQ10 significantly improved neurological behavior and reduced weight loss up to 7 days after tMCAO (P < 0.05). Furthermore, CoQ10 reduced cerebral infarct volumes by 67% at 24 hours after tMCAO and 35% at 7 days (P < 0.05). Cerebral ischemia resulted in a significant reduction in endogenous CoQ10 in both hemispheres (P < 0.05). However, intravenous injection of solubilized CoQ10 resulted in its increase in both hemispheres at 24 hours and in the contralateral hemisphere at 7 days (P < 0.05). Our results demonstrate that CoQ10 is a robust neuroprotective agent against ischemia-reperfusion brain injury in rats, improving both functional and morphological indices of brain damage. Topics: Animals; Brain Ischemia; Cerebral Infarction; Injections, Intravenous; Male; Nervous System Diseases; Neuroprotective Agents; Rats; Rats, Wistar; Treatment Outcome; Ubiquinone | 2016 |
[Intravenous injection of coenzyme Q10 increases its level in rat brain].
It is established that intravenous injection of solubilized coenzyme Q10 provides quick and lasting increase in its level in the brain as compared to control intact rats and those with cerebral ischemia. These new data provide a basis for studying the efficacy of coenzyme Q10 as a neuroprotective agent in ischemic stroke. Topics: Animals; Brain; Brain Ischemia; Injections, Intravenous; Male; Neuroprotective Agents; Rats; Rats, Wistar; Stroke; Ubiquinone | 2014 |
[Coenzyme Q10 enhances the expression of Bcl-2 and inhibits the expressions of Bax and GSK-3β in the hippocampus of rats exposed to ischemia/reperfusion injury].
To investigate the effects of coenzyme Q10 pretreatment on the expressions of Bcl-2, Bax and glycogen synthase kinase-3β (GSK-3β) in rats suffering from ischemia/reperfusion injury.. Thirty-six adult male SD rats were randomly assigned into 3 groups: sham-operated group (sham), ischemia/reperfusion group (I/R) and coenzyme Q10 preconditioning group (Q10). Focal cerebral ischemia/reperfusion models were established in experimental rats by blocking middle cerebral artery with suture. Histological changes of hippocampal neurons were observed by HE staining. The expressions of Bcl-2, Bax and GSK-3β were detected by immunohistochemistry and Western blotting.. Immunohistochemistry showed that the percentage of Bcl-2 positive cells increased in the hippocampus, while the percentages of Bax and GSK-3β positive cells decreased in Q10 group compared with I/R group. Western blotting revealed that the expression level of Bcl-2 was higher and the expression levels of Bax and GSK-3β were lower in Q10 group than in I/R group. There were significant differences between the two groups (P<0.05).. Coenzyme Q10 promoted the expression of Bcl-2 and suppressed the expressions of Bax and GSK-3β in the hippocampus of rats exposed to cerebral ischemia/reperfusion. Topics: Animals; bcl-2-Associated X Protein; Brain Ischemia; CA1 Region, Hippocampal; Disease Models, Animal; Gene Expression Regulation; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Male; Proto-Oncogene Proteins c-bcl-2; Rats; Reperfusion Injury; Ubiquinone | 2013 |
Effect of coenzyme Q10 on ischemia and neuronal damage in an experimental traumatic brain-injury model in rats.
Head trauma is one of the most important clinical issues that not only can be fatal and disabling, requiring long-term treatment and care, but also can cause heavy financial burden. Formation or distribution of free oxygen radicals should be decreased to enable fixing of poor neurological outcomes and to prevent neuronal damage secondary to ischemia after trauma. Coenzyme Q₁₀ (CoQ₁₀), a component of the mitochondrial electron transport chain, is a strong antioxidant that plays a role in membrane stabilization. In this study, the role of CoQ₁₀ in the treatment of head trauma is researched by analyzing the histopathological and biochemical effects of CoQ₁₀ administered after experimental traumatic brain injury in rats. A traumatic brain-injury model was created in all rats. Trauma was inflicted on rats by the free fall of an object of 450 g weight from a height of 70 cm on the frontoparietal midline onto a metal disc fixed between the coronal and the lambdoid sutures after a midline incision was carried out.. In the biochemical tests, tissue malondialdehyde (MDA) levels were significantly higher in the traumatic brain-injury group compared to the sham group (p < 0.05). Administration of CoQ₁₀ after trauma was shown to be protective because it significantly lowered the increased MDA levels (p < 0.05). Comparing the superoxide dismutase (SOD) levels of the four groups, trauma + CoQ₁₀ group had SOD levels ranging between those of sham group and traumatic brain-injury group, and no statistically significant increase was detected. Histopathological results showed a statistically significant difference between the CoQ₁₀ and the other trauma-subjected groups with reference to vascular congestion, neuronal loss, nuclear pyknosis, nuclear hyperchromasia, cytoplasmic eosinophilia, and axonal edema (p < 0.05).. Neuronal degenerative findings and the secondary brain damage and ischemia caused by oxidative stress are decreased by CoQ₁₀ use in rats with traumatic brain injury. Topics: Animals; Brain Injuries; Brain Ischemia; Chromatography, High Pressure Liquid; Disease Models, Animal; Neurons; Rats; Ubiquinone; Vitamins | 2011 |
Possible role of vitamin E, coenzyme Q10 and rutin in protection against cerebral ischemia/reperfusion injury in irradiated rats.
To investigate the possible role of vitamin E, coenzyme Q10 and rutin in ameliorating the biochemical changes in brain and serum induced by cerebral ischemia/reperfusion (I/R) in whole body γ-irradiated rats.. Cerebral ischemia was induced in male Wistar rats (either irradiated or non-irradiated) followed by reperfusion.. I/R increased brain content of malondialdehyde (MDA) and depleted its glutathione (GSH) content with a compensatory elevation in cytosolic activities of glutathione peroxidase (GPx) and glutathione reductase (GR) enzymes. It also raised brain cytosolic lactate dehydrogenase (LDH) activity and calcium (Ca(2+)) level. Furthermore, I/R provoked an inflammatory response reflected by an increment in serum levels of the proinflammatory cytokines tumour necrosis factor-α (TNF-α) and interlukin-1β (IL-1β). Moreover, induction of I/R in irradiated rats resulted in a further increase in brain oxidative stress and cytosolic LDH activity, disturbed brain Ca(2+) homeostasis and exaggerated the inflammatory reaction. During irradiation, administration of each of vitamin E, coenzyme Q10 (CoQ10) and rutin to irradiated rats before induction of I/R, alleviated the brain oxidative stress. Moreover, these antioxidants caused attenuation of the rise of the cytosolic activities of GPx and GR. A lowering effect of the cytosolic LDH activity and Ca(2+) level were caused by treatment with antioxidants. Each of vitamin E and rutin revealed an anti-inflammatory action of these antioxidants, while CoQ10 had no effect on serum levels of TNF-α and IL-1β.. These findings indicate that supplementation with either vitamin E, CoQ10 or rutin ameliorated most of the biochemical changes induced by I/R in irradiated rat brain and serum. Topics: Animals; Antioxidants; Brain Ischemia; Gamma Rays; Glutathione; Interleukin-1beta; Male; Malondialdehyde; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Rats, Wistar; Reperfusion Injury; Rutin; Tumor Necrosis Factor-alpha; Ubiquinone; Vitamin E | 2010 |
Mitochondrial calcium transport and mitochondrial dysfunction after global brain ischemia in rat hippocampus.
Here we report effect of ischemia-reperfusion on mitochondrial Ca2+ uptake and activity of complexes I and IV in rat hippocampus. By performing 4-vessel occlusion model of global brain ischemia, we observed that 15 min ischemia led to significant decrease of mitochondrial capacity to accumulate Ca2+ to 80.8% of control whereas rate of Ca2+ uptake was not significantly changed. Reperfusion did not significantly change mitochondrial Ca2+ transport. Ischemia induced progressive inhibition of complex I, affecting final electron transfer to decylubiquinone. Minimal activity of complex I was observed 24 h after ischemia (63% of control). Inhibition of complex IV activity to 80.6% of control was observed 1 h after ischemia. To explain the discrepancy between impact of ischemia on rate of Ca2+ uptake and activities of both complexes, we performed titration experiments to study relationship between inhibition of particular complex and generation of mitochondrial transmembrane potential (DeltaPsi(m)). Generation of a threshold curves showed that complex I and IV activities must be decreased by approximately 40, and 60%, respectively, before significant decline in DeltaPsi(m) was documented. Thus, mitochondrial Ca2+ uptake was not significantly affected by ischemia-reperfusion, apparently due to excess capacity of the complexes I and IV. Inhibition of complex I is favourable of reactive oxygen species (ROS) generation. Maximal oxidative modification of membrane proteins was documented 1 h after ischemia. Although enhanced formation of ROS might contribute to neuronal injury, depressed activities of complex I and IV together with unaltered rate of Ca2+ uptake are conditions favourable of initiation of other cell degenerative pathways like opening of mitochondrial permeability transition pore or apoptosis initiation, and might represent important mechanism of ischemic damage to neurones. Topics: Adaptor Protein Complex 1; Adaptor Protein Complex 4; Animals; Azides; Brain Ischemia; Calcium; Ferricyanides; Hippocampus; Male; Membrane Potentials; Membrane Proteins; Mitochondria; Mitochondrial Diseases; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Rotenone; Spectrometry, Fluorescence; Ubiquinone; Uncoupling Agents | 2009 |
Derivatised alpha-tocopherol as a CoQ10 carrier in a novel water-soluble formulation.
We have derivatised alpha-tocopherol (vitamin E) to a water-soluble polyoxyethanyl-alpha - tocopheryl sebacate (PTS) and discovered that it formed a non-covalent complex with CoQ10 at a molar ratio of 2:1 (PTS-CoQ10). This complex was water-soluble and remained stable for extended periods of time. After oral delivery of the formulation into rats PTS was hydrolysed to vitamin E and elevated levels of both vitamin E and CoQ10 in blood plasma were detected within 1 h. Thus, this aqueous formulation contains a combination of two potent antioxidants. The formulation's efficacy was tested against ischemic brain damage caused by a transient (8 min) bilateral occlusion of the common carotid arteries in rats. The animals received PTS-CoQ10 by two intraperitoneal injections given immediately after ischemia and 3 h later and the brain damage was assessed up to 12 days post-ischemia. A significant neuroprotection was observed in the CA1 hippocampal region, for example at 12 days approximately 50% of CA1 neurons were still alive in the treated animals versus less than 5% in the non-treated group. Our data is consistent with previously published observations indicating the therapeutic potential of antioxidants for treatments of ischemia/reperfusion injuries and the formulation described here is particularly appropriate for the application in acute conditions, such as stroke or cardiac arrest. Topics: Acetates; Alkanes; alpha-Tocopherol; Animals; Antioxidants; Biological Availability; Brain Ischemia; Coenzymes; Ethylamines; Kinetics; Male; Neurons; Neuroprotective Agents; Polyethylene Glycols; Prosencephalon; Rats; Rats, Sprague-Dawley; Ubiquinone | 2003 |
Neuronal death in the rat hippocampus in experimental diabetes and cerebral ischaemia treated with antioxidants.
Male Wistar rats were subjected to intraperitoneal (i.p.) streptozotocin (STZ) administration (85 mg/kg) to evoke diabetes. Cerebral ischaemia was produced by injection of 0.03 ml of air into the left carotid followed by bilateral common carotid ligation. We studied the effect of application of two antioxidants--coenzyme Q10 (CoQ10, 10 mg/kg b.w., i.p. for seven days) and lipoic acid (LA, 100 mg/kg b.w., i.p. for seven days) on neurones and on the apoptosis-related enzyme--caspase-3 activity in the hippocampus and dentate gyrus. Ischaemia and diabetes lead to a decrease of nuclear and perikaryon diameters as well as neuronal density in the CA1, CA2, CA3 and dentate gyrus. Application of CoQ10 or LA for seven days improved the mean nucleus area and perikaryon area in almost all investigated structures. Both antioxidants diminished neuronal loss in the diabetes complicated with ischaemia but not in the animals with diabetes only. Activity of one of the key enzymes in apoptotic cell death, caspase-3 (CPP32), increased in hippocampus in the diabetic rats, in the animals with cerebral ischaemia and in the rats with both diabetes and ischaemia by about 80%, 33% and 53%, respectively. Either the CoQ10 or the LA treatment led to a significant decrease of the CPP32 activity in all experimental groups. Our results confirm the presence of neuronal damage and death in the hippocampus and dentate gyrus in the experimental STZ-diabetes and its aggravation by the additional cerebral ischaemia. The effects of the antioxidative treatment support the hypothesis of an important role of oxidative stress and free radicals in neuronal pathology in diabetes and ischaemia. The above results of CPP32 activity suggest an important role of apoptosis as a mechanism of cell death and demonstrate the positive effect of the CoQ10 and the LA treatment. Topics: Animals; Antioxidants; Apoptosis; Blood Glucose; Brain Ischemia; Caspase 3; Caspases; Cell Count; Coenzymes; Dentate Gyrus; Diabetes Mellitus, Experimental; Free Radicals; Hippocampus; Male; Rats; Rats, Wistar; Thioctic Acid; Ubiquinone | 2001 |
CoQ10 fails to protect brain against focal and global ischemia in rats.
Release of oxygen free radicals occurs following cerebral ischemia. Studies show that oxygen free radicals mediate ischemic brain injury. CoQ10 is a potent free radical scavenger and may offset brain injury associated with reperfusion. We tested exogeneous CoQ10 as a neuroprotectant in rats following both global and focal ischemic insults.. Rats were subjected to either 4-vessel occlusion ischemia (4-VO, 10 min occlusion, 7-day survival) or middle cerebral artery occlusion (MCAO, 120 min-occlusion, 22.5 h survival). Regional cerebral blood flows (rCBF) and physiological variables such as blood pressure, pO2, pCO2, plasma glucose and hematocrit were monitored and measured in focal ischemia. The animals were randomized to receive treatments of either phosphate buffered saline (PBS) vehicle or CoQ10 following global or focal ischemia. Injection times were at the end of ischemia and 3 h later for both models of ischemia. Histological outcomes are expressed as a percentage of hippocampal CA(1) cell injury in global ischemia or percentage of cortical infarct over that of non-ischemic hemisphere in focal ischemia.. In global ischemia, animals treated with PBS vehicle and CoQ10 had 86+/-5% (n=8) and 83+/-10% (n=8), respectively, of hippocampal CA(1) cell injury (P>0.05). The percentage of infarct volumes in animals following focal ischemia were 23+/-9% (control, n=10) and 25+/-9% (CoQ10, n=10). There were no temperature or physiological differences between the two treatment groups.. Acute treatment with CoQ10 via intraperitoneal injection does not prevent neuronal injuries following global and focal ischemia. Topics: Animals; Antioxidants; Brain Ischemia; Cell Death; Coenzymes; Drug Evaluation, Preclinical; Hippocampus; Male; Neurons; Rats; Rats, Wistar; Ubiquinone | 2000 |
Effect of coenzyme Q(10) on biochemical and morphological changes in experimental ischemia in the rat brain.
The aim of the work was to evaluate an influence of CoQ(10) on lactate acidosis, adenosine-5'-triphosphate (ATP) concentrations, oxidized to reduced glutathione ratio and on superoxide dismutase activity in endothelin model of cerebral ischemia in the rat. Light microscopic studies in the central nervous system and morphometric analysis of pyramidal cells in the hippocampus were also performed. Endothelins (ET-1 or ET-3; 20 pmoles) were injected into the right lateral cerebral ventricle (intracerebroventricularly). CoQ(10) was given intraperitoneally (i.p.) just before the operation (i.p. 10 mgkg b. wt.). More severe changes of investigated biochemical parameters were observed in the animals treated with ET-1 in comparison with ET-3. Recovery was noted earlier in the group subjected to ET-3 and CoQ(10) administration, than in the animals subjected to ET-1 and CoQ(10) treatment. Histopathological observations showed sparse foci of a neuronal loss in the cerebral cortex and in the hippocampus only in the ET-1 model of ischemia. Additionally more numerous dark neurons were present in above brain structures following ET-1 administration comparing with ET-3 one. Morphometrical studies demonstrated that CoQ(10) diminished neuronal injury in the hippocampal CA1, CA2 and CA3 zones. Above data indicate on neuroprotective effect of CoQ(10) as a potent antioxidant and oxygen derived free radicals scavenger in the cerebral ischemia. Topics: Adenosine Triphosphate; Animals; Brain; Brain Ischemia; Brain Stem; Cerebellum; Cerebral Cortex; Cerebral Ventricles; Coenzymes; Disease Models, Animal; Endothelin-1; Functional Laterality; Glutathione; Glutathione Disulfide; Hippocampus; Injections, Intraventricular; Lactates; Male; Neurons; Pyramidal Cells; Rats; Rats, Wistar; Superoxide Dismutase; Ubiquinone | 2000 |
Antioxidant role of endogenous coenzyme Q against the ischemia and reperfusion-induced lipid peroxidation in fetal rat brain.
Ischemia and subsequent reperfusion induce lipid peroxidation in the cerebrum of the fetal rat. The present study evaluated the antioxidant activity of endogenous coenzyme Q in protecting against the lipid peroxidation induced in the fetal rat brain by ischemia/reperfusion.. We used wistar rats at day 19 of pregnancy. Fetal ischemia was induced by bilateral occlusion of the utero-ovarian artery for 20 minutes. For reperfusion, the occlusion was released and the circulation was restored for 30 minutes. Control rats underwent sham operation. We determined the levels of thiobarbituric acid-reactive substances, the concentrations of coenzyme Q9, coenzyme Q10, and the mitochondrial respiratory control index in fetal brains.. Occlusion for 20 minutes significantly reduced the respiratory control index (p < 0.01), but did not alter the levels of thiobarbituric acid-reactive substances, coenzyme Q9 or coenzyme Q10. Subsequent reperfusion, however, significantly increased the level of thiobarbituric acid-reactive substances (from 6.53+/-1.54 to 11.46+/-3.31 nM/mg of protein, p < 0.01) and significantly decreased the level of coenzyme Q9 (from 291.73+/-108.94 to 162.44+/-56.83 pM/mg of protein, p < 0.05) and that of coenzyme Q10 (from 153.10+/-75.24 to 79.84+/-30.40 pM/mg of protein, p < 0.05). The respiratory control index was still significantly lower following reperfusion than in controls (p < 0.01). Significant negative correlations were observed between the level of thiobarbituric acid-reactive substances and the concentrations of either coenzyme Q9 (r = -0.68, p < 0.001) or coenzyme Q10 (r = -0.70, p < 0.001).. Endogenous coenzyme Q may protect the fetal rat brain against the lipid peroxidation induced by ischemia/reperfusion. Topics: Animals; Brain Ischemia; Disease Models, Animal; Female; Fetal Hypoxia; Lipid Peroxidation; Mitochondria; Oxygen Consumption; Pregnancy; Rats; Rats, Wistar; Reperfusion Injury; Thiobarbituric Acid Reactive Substances; Ubiquinone | 1999 |
Effect of coenzyme Q10 (CoQ10) on superoxide dismutase activity in ET-1 and ET-3 experimental models of cerebral ischemia in the rat.
The aim of the work was to evaluate the influence of CoQ10 on superoxide dismutase (SOD) activity levels in the rat model of cerebral ischemia induced by endothelins (ET-1 or ET-3). ETs (20 pmol) were injected into the right lateral cerebral ventricle and immediately CoQ10 was given intraperitoneally (10 mg/kg b.w.). In the brains of experimental animals subjected both to ET-1 and ET-2 administration there was observed a decrease of SOD activity in the brain stem, in the cerebrallum and in the cerebral cortex at all time intervals. ET-1, as compared to ET-3 evoked longer lasting disturbances in SOD activity. In the cerebellum and in the cerebral cortex positive effect of CoQ10 and recovery to the control values was noted after 4 hours in the group subjected to ET-3 injection and after 24 hours in the ET-1 treated animal. Investigated brain areas showed different sensitivity to ETs. Above data may indicate on beneficial effect CoQ10 in the cerebral ischemia via decrease of free radicals concentration. Topics: Animals; Brain Ischemia; Brain Stem; Cerebellum; Cerebral Cortex; Coenzymes; Disease Models, Animal; Endothelin-1; Endothelin-3; Male; Rats; Rats, Wistar; Superoxide Dismutase; Ubiquinone | 1999 |
Evaluation of morphological changes after treatment with coenzyme Q10 (CoQ10) in endothelin-1 induced experimental ischemia in the rat.
The aim of the work was to evaluate the effect of CoQ10 (10 mg/kg body weight) on the morphological changes in the rat brain after the Et-1 induced cerebral ischemia. Selective necrotic foci and dark neurons were observed in the cerebral cortex, hippocampal CA1, CA2 sectors and dentate gyrus after the administration of Et-1. Around the necrotic foci, glycogen was deposited 24 hours after the ischemic hypoxia. It seems that histopathological changes evoked by Et-1 indicate the complicated mechanism connected with ischemia. After treatment with CoQ10 only sparse neuronal changes were observed. CoQ10, known oxygen-derived free radicals scavenger diminished neuronal damage in the cerebral cortex and in the hippocampus. Topics: Animals; Brain; Brain Ischemia; Cerebral Cortex; Dentate Gyrus; Endothelin-1; Hippocampus; Male; Neurons; Neuroprotective Agents; Rats; Rats, Wistar; Reactive Oxygen Species; Ubiquinone | 1998 |
Changes in amyloid precursor protein and apolipoprotein E immunoreactivity following ischemic brain injury in rat with long-term survival: influence of idebenone treatment.
We observed in extra- and intracellular space accumulation of different fragments of amyloid precursor protein (APP) and apolipoprotein E (Apo E) in rat brain after cardiac arrest with long-term survival. Idebenone treatment did not affect APP and Apo E alterations in this condition. Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Apolipoproteins E; Benzoquinones; Brain Ischemia; Cerebral Cortex; Female; Hippocampus; Rats; Rats, Wistar; Ubiquinone | 1997 |
[An increase in cerebrospinal fluid ubiquitin in human global brain ischemia--a prognostic marker for anoxic-ischemic encephalopathy].
The prognostic value of ubiquitin levels in cerebrospinal fluid (CSF) was studied in human global brain ischemia (anoxic-ischemic encephalopathy). Twenty four samples were collected from 13 patients who were resuscitated from cardio-pulmonary arrest and survived for at least 1 day. The outcome was classified according to the Glasgow Outcome Scale (GOS1-5). The ubiquitin levels (normal: 14.3 +/- 1.1 ng/ml, mean +/- S.E.M.) in neurologically symptomatic patients (GOS1-4) were 151 +/- 32.5 ng/ml on day 1-2 and elevated to 1,960 +/- 849 ng/ml on day 3-4. The Spearman's rank correlation of ubiquitin levels on day 3-4 and the GOS was -0.855, showing a better correlation than CSF neuron-specific enolase levels (r = -0.846). Ubiquitin is a heat shock protein associated with the degradation of abnormal cellular proteins. Thus, the elevation of CSF ubiquitin levels represents both its overproduction by a cytoprotective response to brain ischemia and its leakage from the damaged tissue. The present study suggests that the measurement of CSF ubiquitin level is useful for the early prognostic assessment of global brain ischemia. Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Brain Death; Brain Ischemia; Female; Humans; Male; Middle Aged; Prognosis; Ubiquinone | 1997 |
Biochemical and histochemical studies of the effects of cerebral metabolism-improving drugs on NADPH diaphorase activity in mouse brain.
The effects of cerebral metabolism-improving drugs on NADPH diaphorase activity in the mouse brain were studied, and we found that diaphorase activity in the post-mitochondrial fraction of brain homogenate was enhanced by idebenone in a concentration-dependent manner. Histochemical studies also indicated that diaphorase staining was intensified by idebenone at the same concentration. These results suggest that idebenone may stimulate the production of nitric oxide, probably through its direct action on nitric oxide synthase, thus producing its protective action on neurological disorders due to cerebral hypoxia or ischemia as a consequence of dilating the cerebral blood vessels. Topics: Amino Acid Oxidoreductases; Animals; Benzoquinones; Brain; Brain Ischemia; Cerebral Cortex; Choroid Plexus; Dose-Response Relationship, Drug; Histocytochemistry; Hypoxia; In Vitro Techniques; Male; Mice; NADPH Dehydrogenase; Nitric Oxide; Nitric Oxide Synthase; Ubiquinone | 1994 |
Effect of idebenone on adenosine outflow and adenine nucleotide level in hippocampal slices under ischemia-like conditions.
The effect of idebenone on the changes in adenosine and nucleotide metabolism occurring in hippocampal slices after ischemia-like conditions (superfusion with glucose-free Krebs solution gassed with 95% N2-5% CO2) and during reperfusion with normal Krebs solution was investigated by measuring adenosine and inosine outflow, and adenosine and adenine nucleotide levels by HPLC. Five minutes of ischemia-like conditions brought about an 8- and 4-fold increase in adenosine and inosine outflow 10 min after reperfusion and a 75% increase in the tissue level of adenosine, a 40% decrease in ATP, and a 50% increase in AMP at the end of the ischemic period. Ten minutes after reperfusion, ATP and AMP returned to control values. Idebenone (25-100 microM) brought about a concentration-dependent increase in adenosine and inosine outflow evoked by ischemia-like conditions. Idebenone (50 microM) also increased the adenosine content in hippocampal slices after both ischemia (+150%) and reperfusion (+320%). An 82% increase in ADP, 174% in AMP, and 56% in the total sum of nucleotides, 10 min after reperfusion were found in idebenone treated slices. These results suggest that idebenone enhances adenosine formation after ischemia-like conditions from sources other than AMP, and improves phosphorylating activity during reperfusion. Idebenone, by increasing adenosine and total nucleotide levels, may protect brain tissue from ischemic damage. Topics: Adenine Nucleotides; Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Benzoquinones; Brain Ischemia; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Hippocampus; In Vitro Techniques; Inosine; Male; Rats; Rats, Wistar; Ubiquinone | 1993 |
Effects of BMY-21502 on anoxia in mice.
The protective effects of BMY-21502 (1-[[1-[2-(trifluoromethyl)-4-pyrimidinyl]-4-piperidinyl]methyl]-2- pyrrolidinone) against cerebral anoxia were investigated using various models in mice, in comparison with those of other cerebroactive drugs. Oral administration of BMY-21502 (10-100 mg/kg) significantly prolonged the survival time in KCN (2.4 mg/kg, i.v.)-induced anoxia. Oxiracetam and idebenone exerted similar but weak protection at doses above 100 mg/kg, p.o. and only at a dose of 100 mg/kg, p.o., respectively. Significant protection by BMY-21502 against moderate hypobaric hypoxia was observed at doses of 30 and 100 mg/kg, p.o. Idebenone (100 and 300 mg/kg, p.o.) significantly prolonged the survival time of mice in this model, but oxiracetam (30-300 mg/kg, p.o.) did not. Oral administration of all of these drugs (BMY-21502, 3-300 mg/kg; Oxiracetam, 100-1000 mg/kg; Idebenone, 100-1000 mg/kg) failed to increase the number of gasps and the duration of gasping in the decapitated head of mice as a complete ischemic model. The anti-anoxic effect of BMY-21502 in the KCN-anoxia model was blocked by pretreatment with scopolamine. These findings suggest that BMY-21502 has an anti-anoxic action superior to those of the other cerebroactive drugs used, and activation of the CNS cholinergic system is involved as one of the causative mechanisms for the anti-anoxic effect of BMY-21502. Topics: Animals; Atmospheric Pressure; Benzoquinones; Brain Ischemia; Disease Models, Animal; Hypoxia, Brain; Male; Mice; Potassium Cyanide; Psychotropic Drugs; Pyrimidines; Pyrrolidines; Pyrrolidinones; Scopolamine; Ubiquinone | 1993 |
Neuroprotective effect of WEB 1881 FU (nebracetam) on an ischemia-induced deficit of glucose uptake in rat hippocampal and cerebral cortical slices and CA1 field potential in hippocampal slices.
Effect of WEB 1881 FU (nebracetam) on hypoxia and ischemia-induced impairment of 2-deoxyglucose (2DG) uptake and CA1 field potentials induced by hypoxia and hypoxia/hypoglycemia (ischemia) in rat brain slices was evaluated and compared to the findings obtained with pentobarbital and idebenone. Hippocampal and cortical slices were exposed to 15-20 min of ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced both 30 mM KCl-induced 2DG uptake and CA1 field potentials elicited by the stimulation of Schaffer collaterals in the hippocampus. Pretreatment of nebracetam at 1 mM or pentobarbital at 0.1 mM attenuated a decline of 2DG uptake and CA1 field potentials under the condition of ischemia. In addition, nebracetam and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampus under hypoxia for 45 min. Furthermore, these drugs also attenuated the decline of 2DG uptake induced by 10 mM glutamate for 20 min. However, treatment with idebenone did not recover the deficit of 2DG uptake and CA1 field potential. The present result suggests that nebracetam and pentobarbital exert neuroprotective actions against not only ischemia but also glutamate toxicity. Topics: Animals; Benzoquinones; Brain Ischemia; Cerebral Cortex; Deoxyglucose; Electrophysiology; Evoked Potentials; Glutamates; Glutamic Acid; Hippocampus; Hypoxia; In Vitro Techniques; Male; Parasympathomimetics; Pentobarbital; Pyrrolidinones; Rats; Rats, Inbred Strains; Ubiquinone | 1992 |
Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine hydrochloride on ischemia-induced changes in brain monoamines and their metabolites in gerbils.
Bifemelane hydrochloride (bifemelane), idebenone and indeloxazine hydrochloride (indeloxazine) are used clinically to reduce apathy and other emotional disturbances in patients with cerebrovascular disease. In gerbil brains, ischemia affects many monoaminergic neurotransmitters and their metabolites. In the present study, the effects of treatment with bifemelane, idebenone and indeloxazine on ischemia-induced changes in monoamines and their metabolites were studied in ischemic gerbil brains. Although these drugs had no effect on the monoaminergic neurotransmitters or their metabolites in sham-operated animals, in the ischemic brains both dopamine and serotonin turnovers were abnormal after idebenone or indeloxazine treatment. Bifemelane, in contrast, tended to correct the ischemia-induced changes in the dopaminergic and serotonergic systems in the cerebral cortex, hippocampus and thalamus + midbrain. From the present results and those in previous reports, we conclude that bifemelane is more appropriate than idebenone or indeloxazine as a treatment for the ischemia-induced changes in monoaminergic neurotransmitter systems. Topics: Animals; Benzhydryl Compounds; Benzoquinones; Biogenic Monoamines; Brain Chemistry; Brain Ischemia; Dopamine; Gerbillinae; Hydroxyindoleacetic Acid; Morpholines; Nerve Tissue Proteins; Norepinephrine; Serotonin; Ubiquinone | 1992 |
Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats.
Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2-32 mg/kg IP) as well as idebenone (10-100 mg/kg IP) and physostigmine (0.1-0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems. Topics: Animals; Aziridines; Benzoquinones; Brain Ischemia; Choline; Hippocampus; Injections; Male; Memory; Physostigmine; Psychomotor Performance; Pyridazines; Quinones; Rats; Rats, Inbred Strains; Scopolamine; Ubiquinone | 1990 |
Effects of idebenone on metabolism of monoamines and cyclic AMP formation in rats.
Idebenone, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, at a dose of 100 mg/kg (i.p.) markedly increased the level of 5-hydroxyindole-3-acetic acid (5-HIAA) in several brain regions without affecting monoamine contents in normal rats. In rats with cerebral ischemia, idebenone (10 mg/kg, i.p.) normalized the decreased levels of 5-HIAA in the cerebral cortex, hippocampus, diencephalon and brain stem. A 5-hydroxytryptamine (serotonin, 5-HT) biosynthesis inhibitor, DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) decreased the levels of 5-HT to one-third of the control level 24 h after administration. Idebenone (10, 30, or 100 mg/kg, i.p.), administered 24 h after the treatment with PCPA, accelerated the PCPA-induced 5-HT decreased in the hippocampus, diencephalon and brain stem in a dose-dependent manner. Idebenone (100 mg/kg, i.p.) stimulated the release of 5-HT in the dorsal hippocampus as determined by in vivo differential pulse voltammetry. Idebenone, like p-chloroamphetamine (PCA), stimulated 5-HT release from slices of hippocampus and diencephalon, and the formation of cyclic AMP in a concentration-dependent manner in rat diencephalon slice. This stimulation was almost completely blocked by methysergide, a 5-HT receptor blocker. Idebenone slightly and PCA markedly inhibited 5-HT uptake into hippocampus slices. The mechanism of the 5-HT releasing actions of idebenone in the hippocampal slices may be mediated through endogenous calcium. These results suggest that idebenone has an enhancing effect on the turnover of 5-HT in the hippocampus, diencephalon, and brain stem of rats. Topics: Animals; Benzoquinones; Biogenic Monoamines; Brain; Brain Ischemia; Cyclic AMP; Disease Models, Animal; Fenclonine; Hippocampus; Hydroxyindoleacetic Acid; Indoles; Male; Quinones; Rats; Rats, Inbred Strains; Serotonin; Ubiquinone | 1989 |
Effects of idebenone on neurological deficits, local cerebral blood flow, and energy metabolism in rats with experimental cerebral ischemia.
Improvement of energy metabolism in ischemic cerebral tissue benefits the therapy of occlusive cerebrovascular disorders. In the present study, the effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone) on neurological signs, such as ischemic seizures, lactate and ATP contents of the cerebral cortex, and local cerebral blood flow, were assessed in stroke-prone spontaneously hypertensive rats (SHRSP) with experimentally induced cerebral ischemia. Experimental cerebral ischemia was caused by bilateral carotid artery occlusion (BCAO) in male SHRSP (8-10 weeks old). Pretreatment with idebenone (10-100 mg/kg, p.o.) for 3 or 10 days delayed the onset of ischemic seizure (acute stroke) and prolonged survival time in SHRSP roughly in a dose-dependent manner. When the compound (100 mg/kg, i.p.) was given once 30 min after BCAO, it exerted similar ameliorating effects on the neurological deficits. When idebenone (100 mg/kg for 3 days) was given orally, it did not significantly inhibit the decrease in regional cerebral blood flow induced by BCAO. However, the same treatment markedly inhibited increases in the lactate content and lactate/pyruvate ratio and the decrease in ATP content of the cerebral cortex. The compound did not affect cerebral blood flow in normal rats. These results suggest that idebenone ameliorates the neurological deficits related to cerebral ischemia, and that this effect is mediated by improving cerebral energy metabolism. Topics: Animals; Benzoquinones; Brain; Brain Ischemia; Cerebrovascular Circulation; Disease Models, Animal; Energy Metabolism; Motor Activity; Papaverine; Quinones; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Ubiquinone | 1989 |
Effects of idebenone on memory impairment induced in ischemic and embolization models of cerebrovascular disturbance in rats.
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 | 1989 |
Effects of idebenone on the levels of acetylcholine, choline, free fatty acids, and energy metabolites in the brains of rats with cerebral ischemia.
Cerebral ischemia was induced by a 200-s occlusion of both common carotid arteries in rats in which both vertebral arteries had been permanently cauterized. In the ischemic rats, a significant decrease in acetylcholine (ACh) and a marked increase in choline were observed in the cerebral cortex, hippocampus, striatum, and diencephalon. A slight increase in choline was also observed in the cerebellum and brain stem. Pretreatment with idebenone (10 mg/kg, i.p.) inhibited the decrease in ACh and the increase in choline in the forebrain regions. In addition, the same dose of idebenone inhibited the increments of lactate and free fatty acid contents and tended to inhibit the decrement of the ATP content in the cerebral cortex of the cerebral ischemic rats. These results indicate that idebenone inhibits the alteration of the ACh level and the disruption of membrane phospholipids in the brain of ischemic rats; these effects may be mediated by improved cerebral energy metabolism. Topics: Acetylcholine; Animals; Benzoquinones; Brain; Brain Ischemia; Choline; Disease Models, Animal; Energy Metabolism; Fatty Acids, Nonesterified; Male; Quinones; Rats; Rats, Inbred Strains; Ubiquinone | 1989 |
Lipid peroxidation in focal cerebral ischemia.
To verify whether lipid peroxidation is associated with focal cerebral ischemia, a unilateral middle cerebral artery occlusion was carried out in rats. The concentrations of various endogenous antioxidants in the ischemic center were measured, including alpha-tocopherol and ubiquinones as lipid-soluble antioxidants and ascorbate as a water-soluble antioxidant. At 30 minutes after ischemia, alpha-tocopherol decreased to 79% of baseline, reduced ubiquinone-9 to 73%, ubiquinone-10 to 66%, and reduced ascorbate to 76%. Six hours after ischemia, alpha-tocopherol decreased to 63% and reached a plateau, whereas reduced ubiquinones and reduced ascorbate declined further to 16% and 10%, respectively, 12 hours after ischemia and then reached plateau levels. These results suggest functional and durational differences between antioxidants and lipid peroxidation in this ischemic model. Although the reciprocal increase in oxidized ubiquinones during ischemia was not observed, that of oxidized ascorbate was noted. The complementary antioxidant system between cytoplasmic and membranous components, the combination alpha-tocopherol/ascorbate, was estimated from the calculated consumption ratio of these antioxidants on the basis that the loss of these reduced antioxidants is due to neutralization of free radicals. This system is suggested to play an important role in the early ischemic period. Urate also increased during ischemia. The possible involvement of the xanthine-xanthine oxidase system in initiating free radical reactions in cerebral ischemia is also discussed. Topics: Animals; Ascorbic Acid; Brain; Brain Ischemia; Lipid Peroxides; Male; Rats; Rats, Inbred Strains; Ubiquinone; Uric Acid; Vitamin E | 1989 |
[Lipid peroxidation and changes in xanthine oxidase in cerebral ischemia].
To verify the lipid peroxidation in the focal cerebral ischemia, the levels of alpha-tocopherol, ubiquinone and ascorbate were measured in the ischemic center in rats. The former two were endogeneous lipid soluble antioxidants and the last was a water soluble antioxidant. alpha-Tocopherol, reduced ubiquinone-9 and -10, and reduced ascorbate decreased to 79%, 73%, 66%, and 76% 0.5 hour after ischemia, respectively. alpha-Tocopherol decreased to 63% 6 hours after ischemia, and then reached a plateau, while reduced ubiquinones and reduced ascorbate declined further to 16% and 10% 12 hours after ischemia, respectively, and then reached plateau levels. These results suggest their functional and durational differences as antioxidants against lipid peroxidation in this ischemic model. Although the reciprocal increase in oxidized ubiquinones during ischemia was not observed, that in oxidized ascorbate was noted. The complementary antioxidant system between cytoplasmic and membranous components, the combination alpha-tocopherol/ascorbate, was estimated from the calculated consumption ratio of these antioxidants, assuming that the loss of these reduced antioxidants is due to neutralization of free radicals. This system was suggested to play an important role in an early ischemic period. Urate also markedly increased during ischemia. Therefore, xanthine oxidase activity was measured in rats both in normal brain and in ischemic brain induced by four-vessel occlusion method. In the control rat, the enzyme activity was 0.87 +/- 0.13 nmol/g wet brain/min at 25 degrees C (mean +/- S.D.): 92.4% was associated with the NAD-dependent dehydrogenase form and only 7.6% with the oxygen-dependent superoxide-producing oxidase form. However, the ratio of the latter form increased to 43.7% after 0.5 hour of global ischemia despite the same level in total xanthine oxidase activity. This result suggests the involvement of the oxygen free radicals generated from the xanthine oxidase pathway in the pathogenesis of the ischemic injury of the rat brain. Topics: Animals; Ascorbic Acid; Brain; Brain Ischemia; Ischemic Attack, Transient; Lipid Peroxidation; Male; Oxidation-Reduction; Rats; Rats, Inbred Strains; Ubiquinone; Vitamin E; Xanthine Oxidase | 1989 |
Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine hydrochloride on ischemia-induced depletion of brain acetylcholine levels in gerbils.
Effects of bifemelane hydrochloride, idebenone and indeloxazin hydrochloride on ischemia-induced decrease in acetylcholine (ACh) levels were studied in gerbils. Among these three drugs, only bifemelane hydrochloride significantly inhibited the decrease in ACh concentration in the cerebral cortex, hippocampus and striatum of ischemic gerbils. This suggests that bifemelane hydrochloride has an anti-ischemic action and beneficial effects on various symptoms induced by ischemia. Topics: Acetylcholine; Animals; Benzhydryl Compounds; Benzoquinones; Brain Chemistry; Brain Ischemia; Cerebral Cortex; Corpus Striatum; Gerbillinae; Hippocampus; Humans; Infant, Newborn; Morpholines; Quinones; Ubiquinone | 1988 |
Effects of idebenone (CV-2619) on metabolism of monoamines, especially serotonin, in the brain of normal rats and rats with cerebral ischemia.
The effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619) on the contents, turnover, release and uptake of monoamines, especially serotonin (5-HT), in various brain regions of Wistar rats were studied in vivo and in vitro. In normal rats, an intraperitoneal (i.p.) dose of 100 mg/kg of CV-2619 had no significant effect on the levels of norepinephrine (NE), dopamine (DA) and their metabolites, and 5-HT in the brain regions examined, but it increased the levels of 5-hydroxyindole-3-acetic acid (5-HIAA), the main metabolite of 5-HT, in many brain regions. In rats with cerebral ischemia, a low dose (10 mg/kg, i.p.) of CV-2619 normalized the decreased levels of 5-HIAA in the cerebral cortex, hippocampus, diencephalon and brain stem. A 5-HT biosynthesis inhibitor, DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.), decreased the levels of 5-HT in all brain regions to one-third of the control levels 24 hr after administration in normal rats. CV-2619 (10, 30 or 100 mg/kg, i.p.), administered 24 hr after the treatment with PCPA, accelerated the PCPA-induced 5-HT decreases in the hippocampus, diencephalon and brain stem in a dose-dependent manner. In vitro CV-2619, like p-chloroamphetamine (PCA), stimulated 5-HT release from slices of the hippocampus and diencephalon. CV-2619 slightly inhibited and PCA markedly inhibited 5-HT uptake into hippocampal slices. The mechanism of the 5-HT releasing action of CV-2619 in hippocampal slices seems to be mediated through endogenous calcium. These results suggest that CV-2619 has an enhancing effect on the turnover of 5-HT in the hippocampus, diencephalon and brain stem of rats. Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Benzoquinones; Biogenic Amines; Brain; Brain Ischemia; Chromatography, High Pressure Liquid; Dopamine; Dose-Response Relationship, Drug; Egtazic Acid; Fenclonine; Hippocampus; Homovanillic Acid; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Norepinephrine; Quinones; Rats; Rats, Inbred Strains; Serotonin; Time Factors; Ubiquinone | 1985 |
[Effects of idebenone (CV-2619) on neurological deficits, local cerebral blood flow, and energy metabolism in rats with experimental cerebral ischemia].
Improvement of energy metabolism in ischemic cerebral tissue benefits the therapy of occlusive cerebrovascular lesions. In the present study, the effects of 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone (idebenone, CV-2619) on neurological signs, local cerebral blood flow, and cerebral energy metabolism were assessed in stroke-prone spontaneously hypertensive rats (SHRSP) with bilateral carotid artery occlusion (BCAO). Pretreatment with CV-2619 (10-100 mg/kg, p.o.) for three or ten successive days delayed the onset of ischemic seizure (acute stroke) and prolonged survival time in the SHRSP. When the compound (100 mg/kg, i.p.) was given once 30 min after BCAO, it exerted similar ameliorating effects on the neurological deficits. When CV-2619 (100 mg/kg for 3 days) was given orally, it did not inhibit a decrease in regional cerebral blood flow induced by the carotid artery occlusion. However, the same treatment markedly inhibited increases in lactate content and lactate/pyruvate ratio and a decrease in ATP content in the cerebral cortex. In addition, the compound showed no effect on cerebral blood flow in normal rats. These results suggest that CV-2619 has an ameliorating effect on neurological deficits related with cerebral ischemia, and this effect is mediated by improved cerebral energy metabolism. Topics: Adenosine Triphosphate; Animals; Benzoquinones; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Energy Metabolism; Lactates; Lactic Acid; Male; Quinones; Rats; Seizures; Ubiquinone | 1984 |
Effects of idebenone (CV-2619) on the concentrations of acetylcholine and choline in various brain regions of rats with cerebral ischemia.
The concentrations of acetylcholine (Ach) and choline in various brain regions of rats with and without cerebral ischemia and the effects of 6-(10-hydroxy-decyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619) on the levels of these parameters were investigated. Cerebral ischemia was induced by a 200-sec occlusion of both common carotid arteries in animals in which both vertebral arteries had been permanently cauterized. The concentrations of Ach and choline in the brain were determined by means of pyrolysis gas chromatography. In normal rats, CV-2619 (10, 30 and 100 mg/kg, i.p.) did not alter the concentrations of Ach and choline in the brain regions examined. In the ischemic rats, a significant decrease in Ach and a marked increase in choline were observed in the cerebral cortex, hippocampus, striatum, and diencephalon. A slight increase in the concentration of choline was also observed in the cerebellum and brain stem. Pretreatment with CV-2619 (10 mg/kg, i.p.) inhibited the decrease in Ach and the increase in choline in the forebrain regions. Moreover, the same dose of CV-2619 inhibited the increment of lactate content and tended to inhibit the decrement of ATP content in the cerebral cortex. These results indicate that CV-2619 inhibits alterations of the concentrations of Ach and choline in the brain of the ischemic rats; this inhibition may be due to the ameliorating effect of CV-2619 on the disturbance of cerebral energy metabolism under ischemic conditions. Topics: Acetylcholine; Adenosine Triphosphate; Animals; Benzoquinones; Brain; Brain Ischemia; Choline; Energy Metabolism; Lactates; Lactic Acid; Male; Quinones; Rats; Rats, Inbred Strains; Ubiquinone | 1984 |
Beneficial effect of idebenone (CV-2619) on cerebral ischemia-induced amnesia in rats.
An experimental model of amnesia induced by cerebral ischemia after one-trial passive avoidance learning was established to test the effects of a novel compound, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619), and some commonly used drugs in rats. One day after the vertebral artery was electrocauterized bilaterally, the common carotid artery was transiently occluded bilaterally to produce cerebral ischemia. The amnesia was estimated by the response latency for a rat to step from a light safety compartment to a dark compartment in which a foot-shock was given. The results of the retention test given 24 hr after the ischemia indicated that amnesia was successfully produced when the 200-600 sec ischemia was provided within 20 min after the avoidance learning. The effects of drugs on the amnesia induced by a 200-sec ischemia immediately after the avoidance learning were as follows: CV-2619 (10, 30 mg/kg, i.p. or p.o.) given before the retention test significantly increased the response latency, indicating a reversal effect on the amnesia. Physostigmine (0.1, 0.2 mg/kg, i.p.) and arginine-vasopressin (10 micrograms/kg, s.c.) were also effective, and calcium hopantenate (500 mg/kg, p.o.) showed a slight reversal action. Furthermore, CV-2619 (10 mg/kg, i.p.), given before or after the ischemia, significantly inhibited the appearance of amnesia.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Amnesia; Animals; Arginine Vasopressin; Avoidance Learning; Benzoquinones; Brain Ischemia; Conditioning, Operant; gamma-Aminobutyric Acid; Humans; Male; Pantothenic Acid; Physostigmine; Quinones; Rats; Rats, Inbred Strains; Time Factors; Ubiquinone | 1984 |
alpha-Tocopherol and ubiquinones in rat brain subjected to decapitation ischemia.
Levels of alpha-tocopherol (alpha-Toc), reduced ubiquinones (QH2) and oxidized ubiquinones (Q) were assayed in rat forebrain subjected to decapitation ischemia. Post-decapitation levels of alpha-Toc decreased by 16% at 3 min and 20% at 15 min. Increases in Q9H2 (83%) and in Q10H2 (107%) were observed immediately following decapitation; thereafter their levels began to decrease and approached to the pre-ischemic values at 15 min. In contrast, Q9 and Q10 tended to increase continuously during ischemia. The data indicate that complete ischemia results in distinct changes in the cerebral content of lipid-soluble antioxidants. The decrease of alpha-Toc may make the brain prone to peroxidative attack when cerebral tissue is subsequently reoxygenated. Topics: Animals; Brain Chemistry; Brain Ischemia; Free Radicals; Male; Oxidation-Reduction; Rats; Time Factors; Ubiquinone; Vitamin E | 1983 |
[Brain serotonin metabolism in experimental cerebral ischemia and the effect of coenzyme Q administration].
Bilateral ligation of common carotid arteries of male Wistar rats was produced during fasting for the periods of 15, 30 and 60 min. Thereafter the animals were killed by decapitation, and the brain was divided into the forebrain (ischemic portion), and the brain stem and the cerebellum (blood flow maintained portions by the vertebrobasilar artery system). The above three portions were subjected to fluorophotometry of serotonin (5-HT) and 5-hydroxindole acetic acid (5-HIAA) according to the method described by Curzon. In the different series of the studies, rats pretreated with coenzyme Q (CoQ) were exposed to bilateral ligation of common carotid arteries for 60 min, and the CoQ effect upon the serotonin metabolism was investigated. The results obtained were as follows; 1. The 5-HT levels in the forebrain progressively reduced starting at 15 min (p less than 0.01), and reached to 80.2% of the control value at 60 min (p less than 0.001), while those of the brain stem and the cerebellum showed no significant changes. 2. The time-course changes of 5-HIAA levels up to 60 min were not remarkable in the forebrain and the cerebellum, while those of brain stem revealed a decreasing tendency. 3. CoQ pretreatment to sham-operated rats disclosed a gross increasing trend of 5-HT and 5-HIAA concentrations in the brain stem. 4. CoQ preadministrated brains, of which bilateral common carotid arteries were ligated for 60 min, showed a statistically significant elevation of the 5-HT in the brain stem (p less than 0.01) and in the cerebellum (p less than 0.05), while the 5-HIAA level of CoQ preadministrated brains was higher only in the brain stem as compared to that of shamoperated rats (p less than 0.05). 5. The above results would lead to the hypothesis that CoQ treatment could activate brain serotonin metabolism in case of cerebral infarct. Topics: Animals; Brain; Brain Ischemia; Male; Rats; Rats, Inbred Strains; Serotonin; Ubiquinone | 1983 |
[Effect of recirculation on experimental cerebral ischemia. 3. Therapy].
Topics: Adenosine Triphosphate; Animals; Brain; Brain Ischemia; Carotid Arteries; Cerebrovascular Circulation; Dexamethasone; Glycerol; Hypertension; Lactates; Lactic Acid; Ligation; Male; Pyruvates; Pyruvic Acid; Rats; Rats, Inbred Strains; Ubiquinone | 1982 |