Disease relevance of idebenone

• On the basis of these results, we assessed the effect of idebenone (a free-radical scavenger) in three patients with Friedreich's ataxia [1].
• Remission of Leber's hereditary optic neuropathy with idebenone [2].
• Here, we report a more detailed pathophysiological characterization of our mouse model with isolated cardiac disease by echocardiographic, biochemical and histological studies and its use for placebo-controlled therapeutic trial with Idebenone [3].
• These data demonstrate that idebenone functions as a potent protective hepatocyte antioxidant during hydrophobic bile acid toxicity, perhaps by reducing generation of oxygen free radicals in mitochondria [4].
• Preincubation of the antioxidants, vitamin E (20 microM) and idebenone (10 microM), effectively protected from retinal cell injury after oxidative stress or hypoglycemia, whereas the protection afforded after postincubation of both antioxidants was decreased [5].

Psychiatry related information on idebenone

• Chronic treatment with idebenone (1.5 and 15 mg/kg/day), a cerebral energy metabolism enhancer, over a three-month period, commencing five days after ligation, ameliorated the impairment of water maze learning in rats with common carotid ligation [6].
• The 2-year efficacy and safety of idebenone were studied in a prospective, randomized, double-blind multicentre study in 3 parallel groups of patients with dementia of the Alzheimer type (DAT) of mild to moderate degree [7].
• Sustained efficacy and safety of idebenone in the treatment of Alzheimer's disease: update on a 2-year double-blind multicentre study [7].
• A controlled trial of idebenone in Huntington's disease [8].
• Guinea pigs treated with idebenone showed significantly smaller auditory threshold shifts than unprotected control animals [9].

High impact information on idebenone

• Effect of idebenone on cardiomyopathy in Friedreich's ataxia: a preliminary study [1].
• Conversely, our preliminary findings in patients suggest that idebenone protects heart muscle from iron-induced injury [1].
• Furthermore, we demonstrate that the antioxidant Idebenone delays the cardiac disease onset, progression and death of frataxin deficient animals by 1 week, but does not correct the Fe-S enzyme deficiency [3].
• Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia [3].
• Recently, clinical trials have demonstrated potential benefits from treatment with the antioxidants, vitamin E, selegiline, extract of Gingko biloba, and idebenone [10].

Chemical compound and disease context of idebenone

• The effect of idebenone, a coenzyme Q analogue, on hydrophobic bile acid toxicity to isolated rat hepatocytes and hepatic mitochondria [4].
• Growth of Helicobacter pylori was inhibited by the quinones, idebenone, duroquinone, menadione, juglone, and coenzyme Q(1) at low concentrations of 0.8 to 3.2 mug/ml [11].
• In contrast, piracetam, calcium-hopantenate, idebenone and bifemelane had no significant effect on learned behavior or central monoaminergic function, with the exception of bifemelane which antagonized reserpine-induced hypothermia [12].
• Effects of idebenone (CV-2619) on metabolism of monoamines, especially serotonin, in the brain of normal rats and rats with cerebral ischemia [13].
• Effects of idebenone (CV-2619) on the concentrations of acetylcholine and choline in various brain regions of rats with cerebral ischemia [14].

Biological context of idebenone

• Our results support the view that frataxin is a necessary, albeit non-essential, component of the Fe-S cluster biogenesis, and indicate that Idebenone acts downstream of the primary Fe-S enzyme deficit [3].
• Acceleration of hepatocellular energy by idebenone during early reperfusion after cold preservation ameliorates heat shock protein 70 gene expression in a pig liver model [15].
• Likewise, idebenone inhibits microsomal lipid peroxidation induced by ADP-iron complexes or organic hydroperoxides [16].
• Thus, CV-2619 may contribute to stimulate the net ATP formation by the well-coupling of electron and energy transfer, and by the reduction of non-respiratory oxygen consumption in cerebral metabolism [17].
• Idebenone and vinpocetine augment long-term potentiation in hippocampal slices in the guinea pig [18].

Anatomical context of idebenone

• In freshly isolated rat hepatic mitochondria, when respiration was stimulated by succinate, 10 micromol/l idebenone abrogated the generation of hydroperoxides during a 90-minute exposure to 400 micromol/l GCDC [4].
• Isolated rat hepatocytes in suspension under 9% oxygen atmosphere were preincubated with 0, 50, and 100 micromol/l idebenone for 30 min and then exposed to 1000 micromol/l TCDC for 4 h [4].
• A loss of membrane integrity, evaluated by electron microscopy and by LDH leakage, was observed in peroxidized synaptosomes and it was prevented by pre-incubation with vitamin E (150 microM) and idebenone (50 microM) [19].
• Idebenone protects hepatic microsomes against oxygen radical-mediated damage in organ preservation solutions [20].
• The inactivation of Kupffer cells, the presence or absence of leukocytes, and the suppression of oxidative stress with the antioxidant idebenone, given during reperfusion, had no influence [15].

Associations of idebenone with other chemical compounds

• Chenodeoxycholic acid concentrations increased to 5.15 nmol/10(6) cells after 2 h and to 7.05 after 4 h of incubation of hepatocytes with 1000 micromol/l TCDC, and did not differ in the presence of idebenone [4].
• However, feeding the animals with idebenone over 7 days before explantation led to a faster recovery of ketone body ratio, paralleled by a substantial suppression of HSP70 expression [15].
• There is some evidence to suggest that idebenone might function as an antioxidant; however, it has not been demonstrated whether this function pertains to the quinone or hydroquinone form of idebenone [16].
• We have previously demonstrated that potent antioxidants idebenone and alpha-tocopherol prevent learning and memory impairment in rats which received a continuous intracerebroventricular infusion of amyloid beta, suggesting a role for oxidative stress in amyloid beta-induced learning and memory impairment [21].
• The results indicate that treatment with idebenone provides significant protection against the neuronal degeneration induced by intrastriatal injection of kainic acid and quisqualic acid, but not the NMDA receptor agonist, quinolinic acid [22].

Gene context of idebenone

• For over a year we followed the ophthalmological course of this 24-year-old male with LHON treated with idebenone and vitamin B12 [23].
• The effects of idebenone on the superoxide dismutase, catalase and glutathione peroxidase activities in liver and brain homogenates, as well as in brain synaptosomal and mitochondrial fractions [24].
• Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS [25].
• This effect was rapid, concentration-dependent, maximal at concentrations of 25-50 ng/ml, and mimicked by IGF-II, fibroblast growth factor, and the potent antioxidant idebenone [26].
• In so doing, idebenone prevents the destruction of cytochrome P450, which otherwise would accompany lipid peroxidation [16].

Analytical, diagnostic and therapeutic context of idebenone

• Oral administration of idebenone induces nerve growth factor in the brain and improves learning and memory in basal forebrain-lesioned rats [27].
• Determination of idebenone in rat serum and brain by high-performance liquid chromatography using platinum catalyst reduction and electrochemical detection [28].
• In microdialysis studies, acute administration with idebenone did not affect 5HT and 5HIAA release at any age [29].
• Echocardiography did not confirm a preliminary study reporting improvement of FA-associated cardiomyopathy with idebenone [30].
• By adding idebenone to the coenzyme Q10 therapy, the EEG and Wechsler's Adult Intelligence Scale (WAIS) improved [31].

References