145 research outputs found
Inhibition of human glutathione S-transferase P1-1 by tocopherols and alpha-tocopherol derivatives.
Get PDF: Biochim Biophys Acta 2001 Jul 9;1548(1):23-8 Related Articles, Books, LinkOut Inhibition of human glutathione S-transferase P1-1 by tocopherols and alpha-tocopherol derivatives. Van Haaften RI, Evelo CT, Penders J, Eijnwachter MP, Haenen GR, Bast A. Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, P.O. Box 616, 6200 MD Maastricht, Netherlands. [email protected] alpha-Tocopherol inhibits glutathione S-transferase P1-1 (GST P1-1) (R.I.M. van Haaften, C.T.A. Evelo, G.R.M.M. Haenen, A. Bast, Biochem. Biophys. Res. Commun. 280 (2001)). In various cosmetic and dietary products alpha-tocopherol is added as a tocopherol ester. Therefore we have studied the effect of various tocopherol derivatives on GST P1-1 activity. It was found that GST P1-1 is inhibited, in a concentration dependent manner, by these compounds. Of the compounds tested, the tocopherols were the most potent inhibitors of GST P1-1; the concentration giving 50% inhibition (IC(50)) is <1 microM. The esterified tocopherols and alpha-tocopherol quinone also inhibit the GST P1-1 activity at a very low concentration: for most compounds the IC(50) was below 10 microM. RRR-alpha-Tocopherol acetate lowered the V(max) values, but did not affect the K(m) for either 1-chloro-2,4-dinitrobenzene or GSH. This indicates that the GST P1-1 enzyme is non-competitively inhibited by RRR-alpha-tocopherol acetate. The potential implications of GST P1-1 inhibition by tocopherol and alpha-tocopherol derivatives are discussed
Oxidant metabolism in chronic obstructive pulmonary disease
No full textOxidant metabolism in chronic obstructive pulmonary disease. Boots AW, Haenen GR, Bast A. Dept of Pharmacology and Toxicology, Faculty of Medicine, University of Maastricht, Maastricht, The Netherlands. The development and progression of chronic obstructive pulmonary disease (COPD) have been associated with increased oxidative stress or reduced antioxidant resources. Several indicators of oxidative stress, such as hydrogen peroxide exhalation, lipid peroxidation products and degraded proteins, are indeed elevated in COPD patients. As a result, the antioxidant capacity decreases in COPD patients. The fall in antioxidant capacity of blood from COPD patients should not only be regarded as a reflection of the occurrence of oxidative stress but also as evidence that oxidative stress spreads out to the circulation and can therefore generate a systemic effect. COPD is linked to weight loss and in particular to loss in fat-free mass by skeletal muscle wasting. This systemic effect can be mediated by both oxidative stress and oxidative stress-mediated processes like apoptosis and inflammation. Furthermore, COPD is a predisposition for lung cancer through several mechanisms including oxidative stress and oxidative stress-mediated processes such as inflammation and disruption of genomic integrity. Current therapeutic interventions against the far-reaching consequences of the systemic oxidative stress in chronic obstructive pulmonary disease are not yet optimised. A diet designed to reduce chronic metabolic stress might form an effective therapeutic strategy in chronic obstructive pulmonary diseas
Masking of antioxidant capacity by the interaction of flavonoids with protein.
No full text: Food Chem Toxicol 2001 Aug;39(8):787-91 Related Articles, Books, LinkOut Masking of antioxidant capacity by the interaction of flavonoids with protein. Arts MJ, Haenen GR, Voss HP, Bast A. Department of Pharmacology and Toxicology, Faculty of Medicine, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands. [email protected] The effect of antioxidants is often executed in complex biological mixtures where various interactions may take place. Therefore, the antioxidant capacity of antioxidants in blood plasma is examined. The assay used is the trolox equivalent antioxidant capacity (TEAC). This method gives the antioxidant capacity of a compound by measuring spectrophotometrically the disappearance of the blue/green stable ABTS [2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)] radical, caused by scavenging. The results show that the antioxidant capacity of quercetin, rutin, catechin or 7-monohydroxyethylrutoside (monoHER) and blood plasma is not additive. This is partly due to interactions between the antioxidant and plasma proteins. However, the antioxidant capacity of alpha-tocopherol, which also binds to protein, is not affected by the interaction. This means that besides the antioxidant capacity of the compound itself, the environment in which the antioxidant has to execute his function is important
The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids
No full textThe antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids. Rezk BM, Haenen GR, van der Vijgh WJ, Bast A. Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht P.O. Box 616, 6200 MD Maastricht, The Netherlands. Phloretin is a dihydrochalcone flavonoid that displays a potent antioxidant activity in peroxynitrite scavenging and the inhibition of lipid peroxidation. Comparison with structurally related compounds revealed that the antioxidant pharmacophore of phloretin is 2,6-dihydroxyacetophenone. The potent activity of 2,6-dihydroxyacetophenone is due to stabilisation of its radical via tautomerisation. The antioxidant pharmacophore in the dihydrochalcone phloretin, i.e., the 2,6-dihydroxyacetophenone group, is different from the antioxidant pharmacophores previously reported in flavonoids. (c) 2002 Elsevier Science (USA)
Oxidative damage shifts from lipid peroxidation to thiol arylation by catechol-containing antioxidants
No full textOxidative damage shifts from lipid peroxidation to thiol arylation by catechol-containing antioxidants. Boots AW, Haenen GR, den Hartog GJ, Bast A. Department of Pharmacology and Toxicology, Faculty of Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. [email protected] Catechol-containing antioxidants are able to protect against lipid peroxidation by nonenzymatic scavenging of free radicals with their catechol moiety. During their antioxidant activity, catechol oxidation products such as semiquinone radicals and quinones are formed. These oxidation products of 4-methylcatechol inactivate the GSH-dependent protection against lipid peroxidation and the calcium sequestration in liver microsomes. This effect is probably due to arylation by oxidation products of 4-methylcatechol of free thiol groups of the enzymes responsible for the GSH-dependent protection and calcium sequestration, i.e. the free radical reductase and calcium ATPase. It is concluded that a catechol-containing antioxidant might shift radical damage from lipid peroxidation to sulfhydryl arylatio
Lack of inhibition of endothelial nitric oxide synthase in the isolated rat aorta by doxorubicin
No full textLack of inhibition of endothelial nitric oxide synthase in the isolated rat aorta by doxorubicin. den Hartog GJ, Boots AW, Haenen GR, van der Vijgh WJ, Bast A. Department of Pharmacology and Toxicology, University Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands. [email protected] Besides inducing cardiotoxicity, doxorubicin also affects the vasculature. Recent observations in cultured endothelial cells indicated that the endothelial form of nitric oxide synthase might be inhibited by doxorubicin thereby seriously interfering with vascular function. We have investigated the effect of doxorubicin on the relaxation induced by the muscarinic agonist carbachol in the isolated rat aorta. It was found that doxorubicin at concentrations up to 50 microM does not alter the relaxant response to carbachol. Direct measurement of nitrite, the metabolite of NO*, by the Griess assay confirmed our observation that NO*)production is not inhibited by doxorubici
Transcription factor NF-kappaB as a potential biomarker for oxidative stress.
No full textBr J Nutr 2001 Aug;86 Suppl 1:S121-7 Related Articles, Books, LinkOut Transcription factor NF-kappaB as a potential biomarker for oxidative stress. van den Berg R, Haenen GR, van den Berg H, Bast A. TNO Nutrition and Food Research, P.O. Box 360, 3700 AJ Zeist, Netherlands. [email protected] There is increasing interest in the involvement of transcription factors, such as of the transcription factor NF-kappaB (nuclear factor-kappaB), in the pathogenesis of various diseases. NF-kappaB is involved in the control of the transcription of a variety of cellular genes that regulate the inflammatory response by the production of cytokines, chemokines, cell adhesion molecules and acute phase proteins. The involvement of NF-kappaB is especially of interest as it is activated by oxidative stress and its activation can be modulated by antioxidant compounds. The activation of NF-kappaB can be determined by the electromobility shift assay (EMSA) with a NF-kappaB binding-site-specific probe. EMSA can also be used on human mononuclear cells isolated from peripheral blood, which could make the assay applicable for clinical trials. The critical steps of the EMSA are discussed, addressing some pitfalls of the assay. The procedure that can be used to express NF-kappaB activity in human subjects is evaluated. This offers the possibility to use NF-kappaB as a functional biomarker of oxidative stress as illustrated by several examples of in vitro and in vivo studies
Hypochlorous acid is a potent inhibitor of acetylcholinesterase
No full textHypochlorous acid is a potent inhibitor of acetylcholinesterase. den Hartog GJ, Vegt E, van der Vijgh WJ, Haenen GR, Bast A. Department of Pharmacology and Toxicology, University Maastricht, P.O. Box 616, The Netherlands. [email protected] The role of hydrogen peroxide and peroxynitrite in the induction of airway hyperreactivity has been well described. Another reactive species which is formed during airway inflammation is hypochlorous acid (HOCl). In the present investigation the effect of HOCl on cholinergic innervation of the airway was investigated. It was observed that HOCl was capable of increasing the basal tension of electrically stimulated tracheal smooth muscle. It was found that HOCl inhibits purified acetylcholinesterase with an IC50 value of 0.66 microM. Decreased acetylcholinesterase activity could allow accumulation of acetylcholine and increased airway muscle tension. The effects of HOCl on the isolated organ and the enzyme preparation could be precluded with thiol group-containing compounds such as reduced glutathione and N-acetylcysteine. The present findings indicate that HOCl can act as inhibitor of acetylcholinesterase. The implications of this finding for the induction of airway hyperreactivity are discussed. (c) 2002 Elsevier Science (USA)
alpha-Tocopherol inhibits human glutathione S-transferase pi.
Get PDF: Biochem Biophys Res Commun 2001 Jan 26;280(3):631-3 Related Articles, Books, LinkOut alpha-Tocopherol inhibits human glutathione S-transferase pi. van Haaften RI, Evelo CT, Haenen GR, Bast A. Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, 6200 MD Maastricht, The Netherlands. alpha-Tocopherol is the most important fat-soluble, chain-breaking antioxidant. It is known that interplay between different protective mechanisms occurs. GSTs can catalyze glutathione conjugation with various electrophiles, many of which are toxic. We studied the influence of alpha-tocopherol on the activity of the cytosolic pi isoform of GST. alpha-Tocopherol inhibits glutathione S-transferase pi in a concentration-dependent manner, with an IC(50)-value of 0.5 microM. At alpha-tocopherol additions above 3 microM there was no GST pi activity left. alpha-Tocopherol lowered the V(max) values, but did not affect the K(m) for either CDNB or GSH. This indicates that the GST pi enzyme is noncompetitively inhibited by alpha-tocopherol. An inhibition of GST pi by alpha-tocopherol may have far-reaching implications for the application of vitamin E. Copyright 2001 Academic Press
New method to study oxidative damage and antioxidants in the human small bowel: effects of iron application
Get PDFNew method to study oxidative damage and antioxidants in the human small bowel: effects of iron application. Troost FJ, Saris WH, Haenen GR, Bast A, Brummer RJ. Dept. of Human Biology, Research Institute Maastricht, MaastrichtUniversity, The Netherlands. [email protected] Iron may induce oxidative damage to the intestinal mucosa by its catalyzing role in the formation of highly reactive hydroxyl radicals. This study aimed to determine iron-induced oxidative damage provoked by a single clinical dosage of ferrous sulfate and to elucidate the antioxidant defense mechanisms in the human small intestine in vivo. A double-lumen perfusion tube was positioned orogastrically into a 40-cm segment of the proximal small intestine in six healthy volunteers (25 +/- 5 yr). The segment was perfused with saline and subsequently with saline containing 80 mg iron as ferrous sulfate at a rate of 10 ml/min. Intestinal fluid samples were collected at 15-min intervals. Thiobarbituric acid reactive substances concentrations as an indicator of lipid peroxidation increased significantly from 0.07 microM (range, 0-0.33 microM) during saline perfusion to 3.35 microM (range, 1.19-7.27 microM) during iron perfusion (P < 0.05). Nonprotein antioxidant capacity increased significantly from 474 microM (range, 162-748 microM) to 1,314 microM (range, 674-1,542 microM) (P < 0.05). These data show that a single dosage of ferrous sulfate induces oxidative damage and the subsequent release of an antioxidant in the small intestine in vivo in healthy volunteers
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