ubiquinone and Crohn-Disease

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. All the patients with inflammatory bowel disease were right-handed/left hemispheric dominant by the dichotic listening test. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free-radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by ANOVA. In patients with inflammatory bowel disease there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Inflammatory bowel disease is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation, and autoimmunity and a schizophreniform psychosis important in its pathogenesis. The biochemical patterns obtained in inflammatory bowel disease is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Inflammatory bowel disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Topics: Adult; Analysis of Variance; Colitis, Ulcerative; Crohn Disease; Digoxin; Dolichols; Dominance, Cerebral; Enzyme Inhibitors; Erythrocyte Membrane; Glycoproteins; Glycosaminoglycans; Humans; Hydroxymethylglutaryl CoA Reductases; Hypothalamus; Magnesium; Matched-Pair Analysis; Neurotransmitter Agents; Polyisoprenyl Phosphates; Sodium-Potassium-Exchanging ATPase; Ubiquinone

To assess the status of lipidsoluble antioxidants (carotenoids, tocopherols, ubiquinone), retinol and their correlation with TRAP (total radical-trapping antioxidant potential) in patients with Crohn's disease.. Prospective case-control study.. Clinic of Internal Medicine IV/Department of Gastroenterology and Hepatology, University of Vienna Medical School.. Plasma antioxidant concentrations were determined in patients with Crohn's disease (n = 24) to evaluate the antioxidant capacity compared to healthy controls (n = 33). Additionally, plasma TRAP (total radical-trapping antioxidant potential) was measured in 13 patients and 22 controls.. All investigated carotenoids (alpha-carotene, beta-carotene and cryptoxanthin) were significantly decreased in patients with Crohn's disease (10.2 +/- 9.3, 16.2 +/- 12.4 and 7.8 +/- 5.5 microg/dl) compared to controls (13.3 +/- 5.1, 34.7 +/- 18.8 and 48.5 +/- 38.4 microg/dl respectively), whereas gamma-tocopherol and ubiquinone were significantly elevated in patients (0.14 +/- 0.07 microg/dl and 82.3 +/- 41.5 microg/dl, controls: 0.09 +/- 0.04 microg/dl and 60.8 +/- 30.0 microg/dl, respectively). Retinol and alpha-tocopherol did not significantly differ from controls. The total radical-trapping antioxidant potential (TRAP) was significantly lower in patients (1.11 +/- 0.28 micromol/l) compared to controls (1.34 +/- 0.26 micromol/l). Antioxidants were neither related to duration or severity of disease nor to disease activity.. In patients with Crohn's disease several plasma antioxidant parameters are altered and the total radical-trapping antioxidant potential is decreased.

Topics: Adult; Antioxidants; Carotenoids; Case-Control Studies; Crohn Disease; Female; Humans; Male; Prospective Studies; Severity of Illness Index; Smoking; Solubility; Ubiquinone; Vitamin E

Experimental approaches designed to define the role of reactive oxygen and nitrogen species generated by inflammatory cells in the tissue injury seen in inflammatory bowel disease rarely consider the chemical antioxidant defences against such increased oxidant stress in the mucosa. In this investigation, we have analysed components of the aqueous and lipid phase antioxidant mucosal defences by measuring the total peroxyl radical scavenging capacity and the levels of urate, glutathione, alpha-tocopherol, and ubiquinol-10 in paired noninflamed and inflamed mucosal biopsies from inflammatory bowel disease patients. Compared to paired noninflamed mucosa, decreases were observed in inflamed mucosa for total peroxyl radical scavenging capacity (55%, p = 0.0031), urate [Crohn's disease (CD), 62.2%, p = 0.066; ulcerative colitis (UC), 47.3%, p = 0.031], glutathione (UC, 59%, 7/8 patients, ns), total glutathione (UC 65.2%, 6/8 patients, ns), ubiquinol-10 (CD, 75.7%, p = 0.03; UC, 90.5%, p = 0.005). The mean alpha-tocopherol content was unchanged. These observations support our earlier findings of decreased reduced and total ascorbic acid in inflamed IBD mucosa and demonstrate that the loss of chemical antioxidant defences affects almost all the major components. The decreased antioxidant defences may severely compromise the inflamed mucosa, rendering it more susceptible to oxidative tissue damage, hindering recovery of the mucosa and return of epithelial cell layer integrity. The loss of chemical antioxidant components provides a strong rational for developing novel antioxidant therapies for the treatment of inflammatory bowel disease.

Topics: Antioxidants; Colitis, Ulcerative; Crohn Disease; Free Radical Scavengers; Free Radicals; Glutathione; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Peroxides; Ubiquinone; Uric Acid; Vitamin E

Topics: Colitis, Ulcerative; Colon; Colonic Diseases; Colonic Diseases, Functional; Crohn Disease; Cystic Fibrosis; Diverticulum, Colon; Enterocolitis, Pseudomembranous; Glucosephosphate Dehydrogenase; Glycerolphosphate Dehydrogenase; Histocytochemistry; Humans; Intestinal Mucosa; Intestinal Polyps; Oxidoreductases; Rectal Neoplasms; Succinate Dehydrogenase; Ubiquinone