ubiquinone and Hypoglycemia

Diabetic neuropathic pain is reduced with tight glycemic control. However, strict control increases the risk of hypoglycemic episodes, which are themselves linked to painful neuropathy. This study explored the effects of hypoglycemia-related painful neuropathy. Pretreatment with coenzyme Q10 (CoQ10) was performed to explore the preventive effect of CoQ10 on hypoglycemia-related acute neuropathic pain. Two strains of mice were used and 1 unit/kg of insulin was given to induce hypoglycemia. Mechanical sensitivity of hindpaw withdrawal thresholds was measured using von Frey filaments. Blood glucose levels were clamped at normal levels by joint insulin and glucose injection to test whether insulin itself induced hypersensitivity. Results suggest that the increased mechanical sensitivity after insulin injection is related to decreased blood glucose levels. When blood glucose levels remained at a normal level by the linked administration of insulin and glucose, mice demonstrated no significant change in mechanical sensitivity. Pretreatment with CoQ10 prevented neuropathic pain and the expression of the stress factor c-Fos. These results support the concept that pain in the diabetic scenario can be the result of hypoglycemia and not insulin itself. Additionally, pretreatment with CoQ10 may be a potent preventive method for the development of neuropathic pain.

Topics: Acute Disease; Analgesics; Animals; Biomarkers; Blood Glucose; Disease Models, Animal; Hyperalgesia; Hypoglycemia; Insulin; Mice, Inbred C57BL; Mice, Inbred CBA; Neuralgia; Pain Threshold; Proto-Oncogene Proteins c-fos; Spinal Cord; Time Factors; Ubiquinone

Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once.. We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈ 3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging.. During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay.. NaHB is a highly effective and safe treatment that needs further controlled studies.

Topics: Brain; Carnitine; Child, Preschool; Coma; Consanguinity; Dietary Fats; Hereditary Central Nervous System Demyelinating Diseases; Humans; Hypoglycemia; Ketones; Magnetic Resonance Imaging; Male; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Muscle Weakness; Riboflavin; Treatment Outcome; Ubiquinone

evaluate the psychomotor evolution of a child with Multiple acyl-CoA dehydrogenase deficiency after treatment with L-carnitine, ubiquinone and riboflavin.. an assessment of psychomotor development was performed before the start of farmacological treatment using the Assessment Scale of Mental Development Griffiths (GMDS-R, 0-2 years). The same assessment was performed after a month and after six months of treatment to evaluate the possible benefits of treatment.. we noticed a quick and dramatic improvement in muscular tone and motor performances after pharmacological treatment. We also observed a substantial improvement in the personal/social and hearing/language areas, suggesting the presence of intellectual/cognitive improvement. The clinical improvement correlated with the biochemical response.. In our patient early therapy resulted in a optimal response in psychomotor development, motor function and muscole hypotonia. Evaluation with GMDS-R, a simple, non-invasive and multidimensional tool, represents a useful instrument to monitor the clinical response to treatment.

Topics: Acidosis; Acyl-CoA Dehydrogenase; Amino Acid Metabolism, Inborn Errors; Carnitine; Child Development; Hearing; Humans; Hypoglycemia; Infant; Language Development; Male; Muscle Hypotonia; Muscle, Skeletal; Neuropsychological Tests; Psychomotor Performance; Riboflavin; Social Behavior; Tandem Mass Spectrometry; Ubiquinone; Vitamins

Topics: Adult; Deafness; Diabetes Mellitus, Type 2; DNA, Mitochondrial; Epilepsy; Female; Genes, Mitochondrial; Hearing Loss, Bilateral; Hearing Loss, Conductive; Hearing Loss, Mixed Conductive-Sensorineural; Humans; Hypoglycemia; Insulin; Mitochondrial Diseases; Mutation, Missense; Pedigree; Polymorphism, Restriction Fragment Length; RNA, Transfer, Leu; Ubiquinone

A role for the antioxidants vitamin E and idebenone in decreasing retinal cell injury, after metabolic inhibition induced by chemical ischemia and hypoglycemia, was investigated and compared with oxidative stress conditions. 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. Delayed retinal cell damage, mediated by chemical ischemia, was attenuated at 10 or 12 h postischemia, only after exposure to the antioxidants during all the experimental procedure. An antagonist of the N-methyl-D-aspartate (NMDA) receptors, an inhibitor of nitric oxide synthase (NOS) or a blocker of L-type Ca2+ channels were ineffective in reducing cell injury induced by chemical ischemia, hypoglycemia or oxidative stress. Oxidative stress and hypoglycemia increased (about 1.2-fold) significantly the fluorescence of the probe DCFH2-DA, that is indicative of intracellular ROS formation. Free radical generation detected with the probe dihydrorhodamine 123 (DHR 123) was enhanced after oxidative stress, chemical ischemia or hypoglycemia (about 2-fold). Nevertheless, the antioxidants vitamin E or idebenone were ineffective against intracellular ROS generation. Cellular energy charge decreased greatly after chemical ischemia, was moderately affected after hypoglycemia, but no significant changes were observed after oxidative stress. Preincubation with vitamin E prevented the changes in energy charge upon 6 h posthypoglycemia. We can conclude that irreversible changes occurring during chemical ischemia mainly reflect the alterations taking place at the ischemic core, whereas hypoglycemia situations may reflect changes occurring at the penumbra area, whereby vitamin E or idebenone may help to increase cell survival, exerting a beneficial neuroprotective effect.

Topics: Animals; Antioxidants; Benzoquinones; Calcium Channel Blockers; Cells, Cultured; Chick Embryo; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Free Radicals; Hypoglycemia; Ischemia; Neurons; Oxidative Stress; Reactive Oxygen Species; Retina; Ubiquinone; Vitamin E

The effect of energetic metabolism compromise, obtained by chemical induction of hypoglycaemia (glucose deprivation), hypoxia (mitochondrial respiratory chain inhibition), and ischaemia (hypoglycaemia plus hypoxia), on glutamate toxicity was analyzed on PC12 cells. The respiratory status of these cells, measured by the MTT [3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide] assay, was significantly decreased after metabolic inhibition induced by ischaemia, but it was not affected by both hypoglycaemia and hypoxia. Under hypoglycaemia, but not under hypoxia, ATP levels were significantly reduced (from 12.67+/-0.48 to 5.38+/-1.41 nmol/mg protein). However, ischaemic-like conditions greatly potentiated the decline of ATP levels (95% decrease) observed after hypoglycaemia. The influence of metabolic inhibition on glutamate-induced cytotoxicity was also analyzed. When the cells were preincubated under conditions that deplete ATP (hypoglycaemia and ischaemia), the inhibition of MTT reduction, measured after glutamate incubation, was potentiated. This effect could be reverted when vitamin E and idebenone were present during the induction of metabolic inhibition. The ATP levels above which glutamate susceptibility was enhanced were also determined. These results indicate that glutamate toxicity on PC12 cells, which occurs by a mechanism independent of N-methyl-D-aspartate (NMDA) receptor activation, can be enhanced by the depletion of intracellular ATP upon metabolic stress; it is dependent on the extent of ATP depletion and seems to involve the generation of free radicals. It can be concluded that under ischaemic conditions, the deleterious effects of glutamate can be potentiated by the energetic compromise associated with this pathologic situation.

Topics: Adenosine Triphosphate; Animals; Antioxidants; Benzoquinones; Cell Hypoxia; Disease Susceptibility; Energy Metabolism; Glutamic Acid; Hypoglycemia; Ischemia; Mitochondria; PC12 Cells; Rats; Receptors, N-Methyl-D-Aspartate; Tetrazolium Salts; Thiazoles; Ubiquinone; Vitamin E

Effect of WEB 1881 FU on hypoglycemia/hypoxia-induced brain damage in rats was evaluated and compared to findings obtained with idebenone. We used an in vitro model that facilitated the direct monitoring of dopamine release from striatal slices. The response to high K+ stimulation under perfusion of the slices with D-glucose-free Ringer solution (hypoglycemia) decreased at 40 min, and then practically disappeared. WEB 1881 FU at 10(-6) M or idebenone at 10(-6) M significantly protected against impairment of the striatal responses under the conditions of hypoglycemia. Hypoglycemic injury, evidenced by a remarkable neuron loss, necrosis and spongyosis was also ameliorated by these drugs. WEB 1881 FU at 10(-6) M had a protective action against the impairment of striatal responses evoked by NaCN (electron transport inhibitor at site 3) and oligomycin (inhibitor of mitochondrial ATP synthesis), but idebenone at 10(-6) M did not. In light of these observations, the possibility that WEB 1881 FU and idebenone exert neuroprotective actions against hypoglycemic/hypoxic brain injury by activating energy metabolism with different mechanisms from each other has to be considered.

Topics: Animals; Benzoquinones; Brain Diseases; Corpus Striatum; Cyanides; Dopamine; Hypoglycemia; Hypoxia; In Vitro Techniques; Male; Neurons; Oligomycins; Parasympatholytics; Potassium; Pyrrolidinones; Quinones; Rats; Rats, Inbred Strains; Ubiquinone

Topics: Animals; Hydrocarbons, Iodinated; Hypoglycemia; Kinetics; Mitochondria, Liver; NADH, NADPH Oxidoreductases; Onium Compounds; Quinone Reductases; Rats; Ubiquinone