Hardeland, Rüdiger

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","ARZNEIMITTELFORSCHUNG-DRUG RESEARCH"],["dc.bibliographiccitation.lastpage","10"],["dc.bibliographiccitation.volume","58"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Srinivasan, Venkataramanujan"],["dc.contributor.author","Trakht, Ilya"],["dc.contributor.author","Pandi-Perumal, Seithikurippu R."],["dc.contributor.author","Cardinali, Daniel P."],["dc.date.accessioned","2018-11-07T11:19:27Z"],["dc.date.available","2018-11-07T11:19:27Z"],["dc.date.issued","2008"],["dc.description.abstract","Melatonin (CAS 73-31-4) has both hypnotic and sleep/wake rhythm regulating properties. These sleep promoting actions, which are already demonstrable in healthy humans, have been found useful in subjects suffering from circadian rhythm sleep disorders (CRSD) like delayed sleep phase syndrome (DSPS), jet lag and shift-work sleep disorder. Low nocturnal melatonin production and secretion have been documented in elderly insomniacs, and exogenous melatonin has been shown to be beneficial in treating sleep disturbances of these patients. In comparison to a number of sleep-promoting compounds that are usually prescribed, such as bertzodiazepines and z-drugs (zolpidem and zopiclon belonging to the latter ones), melatonin has several advantages of clinical value: it does not cause hangover nor withdrawal effects and is devoid of any addictive potential. However, recent meta-analyses revealed that melatonin is not sufficiently effective in treating most primary sleep disorders. Some of the reasons for a limited efficacy of this natural hormone are related to its extremely short half-life in the circulation, and to the fact that sleep maintenance is also regulated by mechanisms downstream of primary melatonergic actions. Hence, there is an urgent need for the development of melatonin receptor agonists with a longer half-life, which could be suitable for a successful treatment of insomnia. Such requirements are fulfilled by rarnelteon (CAS 196597-26-9), which possesses a high affinity for the melatonin receptors MT1 and MT2 present in the circadian pacemaker, the suprachiasmatic nucleus (SCN). Ramelteon also has a substantially longer half-life than melatonin. This new drug has been successfully used in treating elderly insomniacs without any adverse effects reported, and is promising for treating patients with primary insomnia and also those suffering from CRSD. Since sleep disturbances constitute the most prevalent symptoms of various forms of depression, the need for the development of an ideal antidepressant was felt, which would both improve sleep and mitigate depressive symptoms. Since most of the currently used antidepressants, including the selective serotonin re-uptake inhibitors worsen the sleep disturbances of depressive patients, another novel melatonergic drug, agomelatine (CAS 13811276-2), holds some promise because of its particular combination of actions: it has a high affinity for MT, and MT2 receptors in the SCN, but it acts additionally as a 5-HT2C antagonist 15-hydroxytryptamine (serotonin) receptor 2C antagonist]. The latter property, which is decisive for the antidepressive action, would not favor but potentially antagonize sleep, but this is overcome during night by the melatonergic, sleep-promoting effect. This drug has been found beneficial in treating patients with major depressive and seasonal affective disorders. Unlike the other antidepressants, agomelatine improves both sleep and clinical symptoms of depressive illness and does not have any of the side effects on sleep seen with other compounds in use. This property seems to be of particular value because of the aggravating effects of disturbed sleep in the development of depressive symptoms. Based on these facts, agomelatine seems to be a drug of superior efficacy with a promising future in the treatment of depressive disorders. However, long-term safety studies are required for both ramelteon and agomelatine, with a consideration of the pharmacology of their metabolites, their effects on redox metabolism, and of eventual undesired mlatonergic effects, e. g., on reproductive functions. According to current data, both compounds seem to be safe during short-term treatment."],["dc.identifier.isi","000253402100001"],["dc.identifier.pmid","18368944"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55285"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.relation.issn","1616-7066"],["dc.relation.issn","0004-4172"],["dc.title","Melatonergic drugs in clinical practice"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","251"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Pineal Research"],["dc.bibliographiccitation.lastpage","260"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Guenther, A. L."],["dc.contributor.author","Schmidt, S. I."],["dc.contributor.author","Laatsch, Hartmut"],["dc.contributor.author","Fotso, Serge"],["dc.contributor.author","Ness, H."],["dc.contributor.author","Ressmeyer, A. R."],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Hardeland, Ruediger"],["dc.date.accessioned","2018-11-07T10:55:28Z"],["dc.date.available","2018-11-07T10:55:28Z"],["dc.date.issued","2005"],["dc.description.abstract","The melatonin metabolite N-1-acetyl-5-methoxykynuramine (AMK) was found to be unstable in air when adsorbed on a thin-layer silica gel chromatography plate, a result that is in good agreement with the relatively high reactivity of this compound. Three novel main products were separated from the reaction mixture and identified by mass spectrometry and nuclear magnetic resonance data as: (i) 3-acetamidomethyl-6-methoxycinnolinone (AMMC), (ii) 3-nitro-AMK (AMNK, N-1-acetyl-5-methoxy-3-nitrokynuramine), and (iii) N-[2-(6-methoxyquinazolin-4-yl)-ethyl]-acetamide (MQA). AMMC and AMNK are shown to be nonenzymatically formed also in solution, by nitric oxide (NO) in the first case, and by a mixture of peroxynitrite and hydrogen carbonate, in the second one. The use of three different NO donors, PAPA-NONOate, S-nitroso-N-acetylpenicillamine and sodium nitroprussiate led to essentially the same results, with regard to a highly preferential formation of AMMC; AMNK was not detected in these reaction systems. Competition experiments with the NO scavenger N-acetylcysteine indicate a somewhat lower reactivity compared with the competitor. Peroxynitrite led to AMNK formation in the presence of physiological concentrations of hydrogen carbonate at pH 7.4, but not in its absence, indicating that nitration involves a mixture of carbonate radicals and NO2, formed from the peroxynitrite-CO2 adduct. No AMMC was detected after AMK exposure to peroxynitrite. Both AMNK and AMMC exhibited a much lower reactivity toward 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) cation radicals than did AMK. In a competition assay for hydroxyl radicals, AMMC showed prooxidant properties, whereas AMNK was a moderate antioxidant. AMMC and AMNK should represent relatively stable physiological products, although their rates of synthesis are still unknown and may be low. Formation of these compounds may contribute to the disappearance of AMK from tissues and body fluids."],["dc.identifier.doi","10.1111/j.1600-079X.2005.00242.x"],["dc.identifier.isi","000231621600006"],["dc.identifier.pmid","16150105"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49793"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1600-079X"],["dc.relation.issn","0742-3098"],["dc.title","Reactions of the melatonin metabolite AMK (N-1-acetyl-5-methoxykynuramine) with reactive nitrogen species: Formation of novel compounds, 3-acetamidomethyl-6-methoxycinnolinone and 3-nitro-AMK"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4849"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Journal of Medicinal Chemistry"],["dc.bibliographiccitation.lastpage","4861"],["dc.bibliographiccitation.volume","53"],["dc.contributor.author","Durand, Gregory"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Ortial, Stephanie"],["dc.contributor.author","Polidori, Ange"],["dc.contributor.author","Villamena, Frederick A."],["dc.contributor.author","Boeker, Jutta"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Pappolla, Miguel A."],["dc.contributor.author","Pucci, Bernard"],["dc.date.accessioned","2018-11-07T08:41:24Z"],["dc.date.available","2018-11-07T08:41:24Z"],["dc.date.issued","2010"],["dc.description.abstract","Our group has demonstrated that the amphiphilic character of alpha-phenyl-N-tert-butyl nitrone based agents is a key feature in determining their bioactivity and protection against oxidative toxicity. In this work, we report the synthesis of a new class of amphiphilic amide nitrones. Their hydroxyl radical scavenging activity and radical reducing potency were shown using ABTS competition and ABTS(center dot+) reduction assays, respectively. Cyclic voltammetry was used to investigate their redox behavior, and the effects of the substitution of the PBN on the charge density of the nitronyl atoms, the electron affinity, and the ionization potential were computationally rationalized. The protective effects of amphiphilic amide nitrones in cell cultures exposed to oxidotoxins greatly exceeded those exerted by the parent compound PBN. They decreased electron and proton leakage as well as hydrogen peroxide formation in isolated rat brain mitochondria at nanomolar concentration. They also significantly enhanced mitochondrial membrane potential. Finally, dopamine-induced inhibition of complex I activity was antagonized by pretreatment with these agents. These findings indicate that amphiphilic amide nitrones are much more than just radical scavenging antioxidants but may act as a new class of bioenergetic agents directly on mitochondrial electron and proton transport."],["dc.identifier.doi","10.1021/jm100212x"],["dc.identifier.isi","000279282300004"],["dc.identifier.pmid","20527971"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19461"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","1520-4804"],["dc.relation.issn","0022-2623"],["dc.title","Amphiphilic Amide Nitrones: A New Class of Protective Agents Acting as Modifiers of Mitochondrial Metabolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","962"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","973"],["dc.bibliographiccitation.volume","95"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Durand, G."],["dc.contributor.author","Polidori, A."],["dc.contributor.author","Pappolla, Miguel A."],["dc.contributor.author","Vega-Naredo, I."],["dc.contributor.author","Coto-Montes, Ana"],["dc.contributor.author","Boker, J."],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Pucci, B."],["dc.date.accessioned","2018-11-07T10:54:43Z"],["dc.date.available","2018-11-07T10:54:43Z"],["dc.date.issued","2005"],["dc.description.abstract","The search for effective treatments that prevent oxidative stress associated with premature ageing and neurodegenerative diseases is an important area of neurochemical research. As age- and disease-related oxidative stress is frequently associated with mitochondrial dysfunction, amphiphilic antioxidant agents of high stability and selectivity that target these organelles can provide on-site protection. Such an amphiphilic nitrone protected human neuroblastoma cells at low micromolar concentrations against oxidative damage and death induced by exposure to the beta-amyloid peptide, hydrogen peroxide and 3-hydroxykynurenine. Daily administration of the antioxidant at a concentration of only 5 mu M significantly increased the lifespan of the individually cultured rotifer Philodina acuticornis odiosa Milne. This compound is unique in its exceptional anti-ageing efficacy, being one order of magnitude more potent than any other compound previously tested on rotifers. The nitrone protected these aquatic animals against the lethal toxicity of hydrogen peroxide and doxorubicin and greatly enhanced their survival when co-administered with these oxidotoxins. These findings indicate that amphiphilic antioxidants have a great potential as neuroprotective agents in preventing the death of cells and organisms exposed to enhanced oxidative stress and damage."],["dc.identifier.doi","10.1111/j.1471-4159.2005.03425.x"],["dc.identifier.isi","000232850000006"],["dc.identifier.pmid","16135084"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49626"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0022-3042"],["dc.title","Mitochondrial medicine: neuroprotection and life extension by the new amphiphilic nitrone LPBNAH acting as a highly potent antioxidant agent"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","33"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Environmental Toxicology"],["dc.bibliographiccitation.lastpage","43"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Riediger, Sonja"],["dc.contributor.author","Behrends, Andreas"],["dc.contributor.author","Croll, Bjoern"],["dc.contributor.author","Vega-Naredo, Ignacio"],["dc.contributor.author","Haenig, Nils"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Boeker, Jutta"],["dc.contributor.author","Grube, Sascha"],["dc.contributor.author","Gipp, Juliane"],["dc.contributor.author","Coto-Montes, Ana"],["dc.contributor.author","Haldar, Chandana"],["dc.contributor.author","Hardeland, Ruediger"],["dc.date.accessioned","2018-11-07T11:05:11Z"],["dc.date.available","2018-11-07T11:05:11Z"],["dc.date.issued","2007"],["dc.description.abstract","The quinalphos metabolite 2-hydroxyquinoxaline (HQO), previously shown to photocatalytically destroy antioxidant vitamins and biogenic amines in vitro, was tested for toxicity in several small aquatic organisms and for mutagenicity in Salmonella typhimurium. In the rotifer Philodina acuticornis, HQO caused the disappearance of large individuals and increased hydroperoxide concentration. The latter effect was not only observed in animals kept in a light/dark cycle, but also in constant darkness, indicating that HQO can assume a reactive state and/or form reactive intermediates under the influence of either light or redox-active metabolites, in particular, free radicals. Cell proliferation was inhibited in the ciliate Paramecium bursaria. In the dinoflagellate Lingulodinium polyedrum, which allows early detection of cellular stress on the basis of bioluminescence measurements, strong rises in light emission became apparent on the 2nd day of exposure to HQO and continued until cells died between 12 and 18 days of treatment. Oxidative damage of protein by HQO was demonstrated by measuring protein carbonyl in L. polyedrum in vivo as well as in light-exposed bovine serum albumin in vitro. In an Ames test of mutagenicity, HQO proved to be genotoxic in both light- and dark-exposed bacteria. HQO appears as a source of secondary quinalphos toxicity, which deserves further attention. (c) 2007 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/tox.20231"],["dc.identifier.isi","000244378400005"],["dc.identifier.pmid","17295279"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52013"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","John Wiley & Sons Inc"],["dc.relation.issn","1520-4081"],["dc.title","Toxicity of the quinalphos metabolite 2-hydroxyquinoxaline: Growth inhibition, induction of oxidative stress, and genotoxicity in test organisms"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","186"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Pineal Research"],["dc.bibliographiccitation.lastpage","187"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Jacob, Sonja"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Sirén, Anna-Leena"],["dc.contributor.author","Hardeland, Rüdiger"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:45:41Z"],["dc.date.available","2017-09-07T11:45:41Z"],["dc.date.issued","2002"],["dc.identifier.doi","10.1034/j.1600-079X.2002.02943.x"],["dc.identifier.gro","3150431"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7194"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.issn","0742-3098"],["dc.title","Melatonin as a candidate compound for neuroprotection in amyotrophic lateral sclerosis (ALS): high tolerability of daily oral melatonin administration in ALS patients"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","The Open Physiology Journal"],["dc.bibliographiccitation.lastpage","22"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Hardeland, Rüdiger"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.date.accessioned","2019-07-09T11:53:10Z"],["dc.date.available","2019-07-09T11:53:10Z"],["dc.date.issued","2008"],["dc.description.abstract","The perception of melatonin as a mediator of darkness, formed in a circadian fashion, circulating in subnanomolar concentrations, and removed as 6-sulfatoxymelatonin, reflects only a sector within a spectrum of actions. This ubiquitous compound present in bacteria and eucaryotes is exceptionally pleiotropic, in terms of binding proteins, receptor distribution, G protein coupling, electron-exchange reactions, and secondary effects by metabolites, such as 5- methoxytryptamine and methoxylated kynuramines. Membrane receptors are located, e.g., in the vertebrate suprachiasmatic nucleus, pars tuberalis, brain, vasculature, and leukocytes. Binding proteins include quinone reductase 2, ROR/RZR transcription factors, calmodulin, calreticulin, nuclear and mitochondrial proteins. Actions via hormonal subsystems, growth factors, neurotransmission and immune system lead to further secondary effects. Single-electron transfer reactions are basis of radical scavenging, non-enzymatic metabolism and interactions with electron transport systems. The metabolite, N1-acetyl-5-methoxykynuramine, is a potent inhibitor of prostaglandin synthesis and of neuronal NO synthase, an NO scavenger and a mitochondrial modulator."],["dc.identifier.doi","10.2174/1874360900901010001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6970"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60355"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1874-3609"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","570"],["dc.title","Melatonin Beyond Its Classical Functions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","374"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Pineal Research"],["dc.bibliographiccitation.lastpage","381"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Rosen, Joachim"],["dc.contributor.author","Than, Ni Ni"],["dc.contributor.author","Koch, Dorothea"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Laatsch, Hartmut"],["dc.contributor.author","Hardeland, Ruediger"],["dc.date.accessioned","2018-11-07T09:02:17Z"],["dc.date.available","2018-11-07T09:02:17Z"],["dc.date.issued","2006"],["dc.description.abstract","Melatonin had previously been shown to reduce up to four 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) cation radicals (ABTS center dot(+)) via a scavenger cascade ending with N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK). However, when melatonin is added to the reaction system in much lower quantities than ABTS center dot(+), the number of radicals scavenged per melatonin molecule is considerably higher and can attain a value of ten. Under conditions allowing for such a stoichiometry, novel products have been detected which derive from AFMK (1). These were separated by repeated chromatography and the major compounds were characterized by spectroscopic methods, such as mass spectrometry (HPLC-MS, EI-MS and ESI-HRMS), H-1 nuclear magnetic resonance (NMR) and C-13 NMR, heteronuclear multiple bond connectivity (HMBC) correlations. The identified substances are formed by re-cyclization and represent 3-indolinones carrying the side chain at C2; the N-formyl group can be maintained, but deformylated analogs seem to be also generated, according to MS. The primary product from AFMK (1) is N-(1-formyl-5-methoxy-3-oxo-2,3-dihydro-1H-indol-2-ylidenemethyl)-acetamide (2), which is obtained after purification as E- and Z-isomers (2a, 2b); a secondary product has been identified as N-(1-formyl-2-hydroxy-5-methoxy-3-oxo-2,3-dihydro-1H-indol-2-ylmethyl)-acetamide (3). When H2O2 is added to the ABTS center dot(+) reaction mixture in quantities not already leading to substantial reduction of this radical, compound 3 is isolated as the major product, whereas 2a and 2b are virtually absent. The substances formed differ from all previously known oxidation products which derive from melatonin and are, among these, the first 3-indolinones. Moreover, the aliphatic side chain at C2 is reminiscent of other substances which have been synthesized in the search for melatonin receptor ligands."],["dc.identifier.doi","10.1111/j.1600-079X.2006.00379.x"],["dc.identifier.isi","000240921200010"],["dc.identifier.pmid","17014695"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24646"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1600-079X"],["dc.relation.issn","0742-3098"],["dc.title","Interactions of melatonin and its metabolites with the ABTS cation radical: extension of the radical scavenger cascade and formation of a novel class of oxidation products, C2-substituted 3-indolinones"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","279"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Redox Report"],["dc.bibliographiccitation.lastpage","288"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Behrends, A."],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Ness, H."],["dc.contributor.author","Grube, S."],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Haldar, C."],["dc.date.accessioned","2018-11-07T10:53:13Z"],["dc.date.available","2018-11-07T10:53:13Z"],["dc.date.issued","2004"],["dc.description.abstract","Toxicity of the pesticide quinalphos may comprise secondary, delayed effects by its main metabolite 2-hydroxyquinoxaline (HQO). We demonstrate that HQO can destroy photocatalytically vitamins C and E, catecholamines, serotonin, melatonin, the melatonin metabolite AMK (N-1-acetyl-5-methoxykynuramine), and unsubstituted and substituted anthranilic acids when exposed to visible light. In order to avoid HQO-independent ascorbate oxidation by light and to exclude actions by hydroxyl radicals, experiments on this vitamin were carried out in ethanolic solutions. Other substances tested ( vitamin E, melatonin, anthranilic acids) were also photocatalytically destroyed by HQO in ethanol. After product analyses had indicated that HQO was not, or only poorly, degraded in the light, despite its catalytic action on other compounds, we followed directly the time course of HQO and ascorbate concentrations in ethanol. While ascorbate was largely destroyed, no change in HQO was demonstrable within 2 h of incubation. Destruction was not prevented by the singlet oxygen quencher DABCO. Obviously, HQO is capable of undergoing a process of organic redox cycling, perhaps via an intermediate quinoxaline-2-oxyl radical. Health problems from HQO intoxication may not only arise from the loss of valuable biomolecules, such as antioxidant vitamins and biogenic amines, but also from the formation of potentially toxic products. Dimerization and oligomerization are involved in several oxidation processes catalyzed by HQO, especially in the indoleamines, in dopamine, and presumably also in vitamin E. Melatonin oxidation by HQO did not only lead to the well-known - and usually protective - metabolite AFMK (N-1-acetyl-N-2-formyl-5-methoxykynuramine), but also to a high number of additional products, among them dimers and trimers. DABCO did not prevent melatonin destruction, but changed the spectrum of products. Serotonin was preferentially converted to a dimer, which can further oligomerize. Several indole dimers are known to be highly neurotoxic, as well as oxidation products formed from catecholamines via the adrenochrome/noradrenochrome pathway. Destruction of melatonin may cause deficiencies in circadian physiology, in immune functions and in antioxidative protection."],["dc.identifier.doi","10.1179/135100004225006759"],["dc.identifier.isi","000225966200006"],["dc.identifier.pmid","15606981"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49303"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Maney Publishing"],["dc.relation.issn","1351-0002"],["dc.title","Photocatalytic actions of the pesticide metabolite 2-hydroxyquinoxaline: destruction of antioxidant vitamins and biogenic amines - implications of organic redox cycling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","ChemInform"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Srinivasan, Venkataramanujan"],["dc.contributor.author","Trakht, Ilya"],["dc.contributor.author","Pandi-Perumal, Seithikurippu R."],["dc.contributor.author","Cardinali, Daniel P."],["dc.date.accessioned","2021-12-08T12:29:39Z"],["dc.date.available","2021-12-08T12:29:39Z"],["dc.date.issued","2008"],["dc.identifier.doi","10.1002/chin.200821264"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/96159"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-476"],["dc.relation.eissn","1522-2667"],["dc.relation.issn","0931-7597"],["dc.rights.uri","http://doi.wiley.com/10.1002/tdm_license_1.1"],["dc.title","ChemInform Abstract: Melatonergic Drugs in Clinical Practice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]