Administration Of Coenzyme Research Articles

Modelling the redox imbalance and oxidative stress in the hippocampus at aluminum neurotoxicity and initiating the coenzyme А biosynthesis

An Alzheimer-like pathological process was induced in mature female Wistar CRL: (WI) WUBR rats using aluminum chloride (200 mg/kg, intragastrically, 6 weeks) in order to model redox imbalance and oxidative stress (OS) in the hippocampus and study the possibilities of their correction 2 weekly administration of coenzyme A biosynthesis modulators (panthenol – PL, pantethine – PT, homopantothenate – HP) at a dose of 200 mg/kg intragastrically for 2 weeks). Against the background of activation of peroxidation processes and a decrease in acetylcholinesterase activity, a decrease in the reduction potential of glutathione and the level of the acid-soluble fraction of CoA was observed with a simultaneous increase in the activity of glutathione-metabolizing enzymes (GR, GPx, GST), the process of S-glutathionylation of proteins and the level of protein thiols. The consumption of the precursors of CoA biosynthesis in full (PL, PT) or in part (HP) had an antioxidant effect, restored the activity of AChE, the level and reduction potential of glutathione and glutathione-metabolizing enzymes, the process of S-glutathionylation, and stimulated the activity of enzymes generating NADPH+. Taking into account the low modulating effect of coenzyme precursors on the level of CoA in the hippocampus and their high redox pharmacological activity, their non-coenzymatic effect on redox mechanisms leading to an increase in the bioavailability of reducing equivalents and energy status is assumed.

Complex-1 activity and 18F-DOPA uptake in genetically engineered mouse model of Parkinson's disease and the neuroprotective role of coenzyme Q 10

Regional distribution of coenzyme Q 10 and mitochondrial complex-1 activity were estimated in the brains of control-(C57BL/6), metallothionein knock out-, metallothionein transgenic-, and homozygous weaver mutant mice; and human dopaminergic (SK-N-SH) cells with a primary objective to determine the neuroprotective potential of coenzyme Q 10 in Parkinson's disease. Complex-1 activity as well as coenzyme Q 10 were significantly higher in the cerebral cortex as compared to the striatum in all the genotypes examined. Complex-1 activity and coenzyme Q 10 were significantly reduced in weaver mutant mice and metallothionein knock out mice, but were significantly increased in metallothionein transgenic mice. The reduced complex-1 activity and 18F-DOPA uptake occurred concomitantly with negligible differences in the coenzyme Q 10 between in the cerebral cortex and striatum of weaver mutant mice. Administration of coenzyme Q 10 increased complex-1 activity and partially improved motoric performance in weaver mutant mice. Direct exposure of rotenone also reduced coenzyme Q 10, complex-1 activity, and mitochondrial membrane potential in SK-N-SH cells. Rotenone-induced down-regulation of complex-1 activity was attenuated by coenzyme Q 10 treatment, suggesting that complex-1 may be down regulated due to depletion of coenzyme Q 10 in the brain. Therefore, metallothionein-induced coenzyme Q 10 synthesis may provide neuroprotection by augmenting mitochondrial complex-1 activity in Parkinson's disease.

Effect of coenzyme Q 10 and vitamin E on brain energy metabolism in the animal model of Huntington's disease

The neuropathological and clinical symptoms of Huntington's disease (HD) can be simulated in animal model with systemic administration of 3-nitropropionic acid (3-NP). Energy defects in HD could be ameliorated by administration of coenzyme Q 10 (CoQ 10), creatine, or nicotinamid. We studied the activity of creatine kinase (CK) and the function of mitochondrial respiratory chain in the brain of aged rats administered with 3-NP with and without previous application of antioxidants CoQ 10 + vitamin E. We used dynamic and steady-state methods of in vivo phosphorus magnetic resonance spectroscopy ( 31P MRS) for determination of the pseudo-first order rate constant ( k for) of the forward CK reaction, the phosphocreatine (PCr) to adenosinetriphosphate (ATP) ratio, intracellular pH i and Mg i 2+ content in the brain. The respiratory chain function of isolated mitochondria was assessed polarographically; the concentration of CoQ 10 and α-tocopherol by HPLC. We found significant elevation of k for in brains of 3-NP rats, reflecting increased rate of CK reaction in cytosol. The function of respiratory chain in the presence of succinate was severely diminished. The activity of cytochromeoxidase and mitochondrial concentration of CoQ 10 was unaltered; tissue content of CoQ 10 was decreased in 3-NP rats. Antioxidants CoQ 10 + vitamin E prevented increase of k for and the decrease of CoQ 10 content in brain tissue, but were ineffective to prevent the decline of respiratory chain function. We suppose that increased activity of CK system could be compensatory to decreased mitochondrial ATP production, and CoQ 10 + vitamin E could prevent the increase of k for after 3-NP treatment likely by activity of CoQ 10 outside the mitochondria. Results of our experiments contributed to elucidation of mechanism of beneficial effect of CoQ 10 administration in HD and showed that the rate constant of CK is a sensitive indicator of brain energy disorder reflecting therapeutic effect of drugs that could be used as a new in vivo biomarker of neurodegenerative diseases.

A Deficiency in Respiratory Complex I in Heart Mitochondria from Vitamin A-Deficient Rats Is Counteracted by an Increase in Coenzyme Q

Defects of NADH:coenzyme Q oxidoreductase (complex I) of mitochondria have been described in many congenital and acquired diseases. Administration of coenzyme Q (CoQ, ubiquinone) has been shown to benefit patients with some of these diseases. However, the mechanisms by which CoQ exerts the therapeutic effects are not clearly understood. A reason could be the lack of saturation of CoQ, in kinetic terms, for complex I activity. However, this hypothesis has not been provedin vivobecause of the difficulty to incorporate CoQ into the mitochondrial membranes. We have found a deficiency in respiratory complex I in heart mitochondria from vitamin A-deficient rats which was accompanied by high CoQ content. The defect in complex I activity was compensated by the increase in CoQ to maintain the mitochondrial electron transfer rate. This finding supports, for the first time in anin vivoexperimental approach, the kinetic hypothesis to explain the short-term therapeutic effects of CoQ.

SOME ASPECTS OF THE METABOLISM OF COENZYME Q IN THE RAT.

Coenzyme Q (ubiquinone) is present in many rat tissues. However, its origin in these tissues, other than liver, is not well established. No deficiency state of coenzyme Q has so far been found. Even when the diet is free of coenzyme Q, tissue concentrations are not affected (Olson, Dialameh & Bentley, 1961; Lawson, Threlfall, Glover & Morton, 1961). The oral administration ofcoenzyme Qlo to rats increased the concentrations of this compound in liver and to a lesser extent in intestines, but no other tissues tested (heart, kidney, lungs, muscle) showed any change (Lawson et al. 1961). Under the conditions employed by Lawson et al. (1961), the absorption of small quantities by the tissues will not be detected and also, if a steady-state concentration of coenzyme Q is maintained, no changes would be observed. An attempt has therefore been made to study the distribution of coenzyme Q in rat tissues, including the foetus, by administering [14C]coenzyme Qlo orally, intracardially and intraperitoneally. Further, the capacity of the rat tissues for the synthesis of

Hepatic uptake and intestinal absorption of Co58-labelled 5,6-dimethylbenzimidazolyl-cobamide coenzyme.

SummaryMeasurements of the hepatic uptake of orally administered Co58-labelled 5,6-dibenzimidazolylcobamide coenzyme suggest that it cannot be absorbed in the intestine in the absence of intrinsic factor and, consequently, cannot be used alone in oral treatment of pernicious anemia, Under similar conditions, less coenzyme than cyanocobalamin is deposited in the liver of patients with pernicious anemia when it is orally administered with active IF preparations from animal stomach. This may be due either to the lessened effect of animal IF preparations on intestinal absorption of coenzyme or to the diminished efficiency of intestinal absorption of coenzyme as compared with that of cyanocobalamin.Surface counting of intestinal areas after oral administration of labelled coenzyme alone and labelled cyanocobalamin to normal subjects and patients with pernicious anemia shows the radioactivity of the intestine to be much more prolonged after administration of coenzyme than after cyanocobalamin. This may be inter...