Hardeland, Rüdiger

[["dc.bibliographiccitation.firstpage","139"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","149"],["dc.bibliographiccitation.volume","165"],["dc.contributor.author","Mayo, J. C."],["dc.contributor.author","Sainz, Rosa M."],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Leon, J."],["dc.contributor.author","Rodriguez, Carmen"],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2018-11-07T11:02:38Z"],["dc.date.available","2018-11-07T11:02:38Z"],["dc.date.issued","2005"],["dc.description.abstract","Inflammation is a complex phenomenon involving multiple cellular and molecular interactions which must be tightly regulated. Cyclooxygenase-2 (COX) is the key enzyme that catalyzes the two sequential steps in the biosynthesis of PGs from arachidonic acid. The inducible isoform of COX, namely COX-2, plays a critical role in the inflammatory response and its over-expression has been associated with several pathologies including neurodegenerative diseases and cancer. Melatonin is the main product of the pineal gland with well documented antioxidant and immuno-modulatory effects. Since the action of the indole on COX-2 has not been previously described, the goal of the present report was to test the effect of melatonin on the activities of COX-2 and inducible nitric oxide synthase (NOS), using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as a model. Melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), prevented COX-2 activation induced by LPS, without affecting COX-1 protein levels. The structurally reviewed compound 6-methoxy-melatonin only partially prevented the increase in COX-2 protein levels induced by the toxin. Likewise melatonin prevented NOS activation and reduced the concentration of products from both enzymes, PGE(2) and nitric oxide. Another energenous antioxidant like N-acetyl-cysteine (NAC) did not reduced COX-2 significantly. The current finding corroborates a role of melatonin as an anti-inflammatory agent and, for the first time, COX-2 and NOS as molecular targets for either melatonin or its metabolites AFM - and AMK. These anti-inflammatory actions seem not to be exclusively mediated by the free radical scavenging properties of melatonin. As a consequence, the present work suggests these substances as a new class of potential anti-inflammatory agents without the classical side effects due to COX-1 inhibition. (C) 2005 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jneuroim.2005.05.002"],["dc.identifier.isi","000230995800015"],["dc.identifier.pmid","15975667"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51426"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-5728"],["dc.title","Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and n1-acetyl-5-methoxykynuramine (AMK), in macrophages"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2294"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Manchester, Lucien C."],["dc.contributor.author","Burkhardt, S."],["dc.contributor.author","Sainz, Rosa M."],["dc.contributor.author","Mayo, J. C."],["dc.contributor.author","Kohen, R."],["dc.contributor.author","Shohami, E."],["dc.contributor.author","Huo, Y. S."],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2018-11-07T08:47:58Z"],["dc.date.available","2018-11-07T08:47:58Z"],["dc.date.issued","2001"],["dc.description.abstract","The biogenic amine N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK) was investigated for its potential antioxidative capacity. AFMK is a metabolite generated through either an enzymatic or a chemical reaction pathway from melatonin. The physiological function of AFMK remains unknown. To our knowledge, this report is the first to document the potent antioxidant action of this biogenic amine. Cyclic voltammetry (CV) shows that AFMK donates two electrons at potentials of 456 mV and 668 mV, and therefore it functions as a reductive force. This function contrasts with all other physiological antioxidants that donate a single electron only when they neutralize free radicals. AFMK reduced 8-hydroxydeoxyguanosine formation induced by the incubation of DNA with oxidants significantly. Lipid peroxidation resulting from free radical damage to rat liver homogenates was also prevented by the addition of AFMK. The inhibitory effects of AFMK on both DNA and lipid damage appear to be dose-response related. In cell culture, AFMK efficiently reduced hippocampal neuronal death induced by either hydrogen peroxide, glutamate, or amyloid beta (25-35) peptide. AFMK is a naturally occurring molecule with potent free radical scavenging capacity (donating two electrons/molecule) and thus may be a valuable new antioxidant for preventing and treating free radical-related disorders."],["dc.identifier.isi","000170809900017"],["dc.identifier.pmid","11511530"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21087"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","0892-6638"],["dc.title","N-1-acetyl-N-2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","627"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Experimental Botany"],["dc.bibliographiccitation.lastpage","646"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Hardeland, Ruediger"],["dc.date.accessioned","2018-11-07T10:01:14Z"],["dc.date.available","2018-11-07T10:01:14Z"],["dc.date.issued","2015"],["dc.description.abstract","Melatonin is synthesized in Alphaproteobacteria, Cyanobacteria, Dinoflagellata, Euglenoidea, Rhodophyta, Phaeophyta, and Viridiplantae. The biosynthetic pathways have been identified in dinoflagellates and plants. Other than in dinoflagellates and animals, tryptophan is not 5-hydroxylated in plants but is first decarboxylated. Serotonin is formed by 5-hydroxylation of tryptamine. Serotonin N-acetyltransferase is localized in plastids and lacks homology to the vertebrate aralkylamine N-acetyltransferase. Melatonin content varies considerably among species, from a few picograms to several micrograms per gram, a strong hint for different actions of this indoleamine. At elevated levels, the common and presumably ancient property as an antioxidant may prevail. Although melatonin exhibits nocturnal maxima in some phototrophs, it is not generally a mediator of the signal 'darkness'. In various plants, its formation is upregulated by visible and/or UV light. Increases are often induced by high or low temperature and several other stressors including drought, salinity, and chemical toxins. In Arabidopsis, melatonin induces cold-and stress-responsive genes. It has been shown to support cold resistance and to delay experimental leaf senescence. Transcriptome data from Arabidopsis indicate upregulation of genes related to ethylene, abscisic acid, jasmonic acid, and salicylic acid. Auxin-like actions have been reported concerning root growth and inhibition, and hypocotyl or coleoptile lengthening, but effects caused by melatonin and auxins can be dissected. Assumptions on roles in flower morphogenesis and fruit ripening are based mainly on concentration changes. Whether or not melatonin will find a place in the phytohormone network depends especially on the identification of molecular signals regulating its synthesis, high-affinity binding sites, and signal transduction pathways."],["dc.identifier.doi","10.1093/jxb/eru386"],["dc.identifier.isi","000351662300002"],["dc.identifier.pmid","25240067"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37973"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1460-2431"],["dc.relation.issn","0022-0957"],["dc.title","Melatonin in plants and other phototrophs: advances and gaps concerning the diversity of functions"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","189"],["dc.bibliographiccitation.journal","Progress in Neuro-Psychopharmacology and Biological Psychiatry"],["dc.bibliographiccitation.lastpage","204"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Brown, Gregory M."],["dc.contributor.author","McIntyre, Roger S."],["dc.contributor.author","Rosenblat, Joshua"],["dc.contributor.author","Hardeland, Rüdiger"],["dc.date.accessioned","2020-12-10T15:20:53Z"],["dc.date.available","2020-12-10T15:20:53Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.pnpbp.2017.04.023"],["dc.identifier.issn","0278-5846"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72840"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Depressive disorders: Processes leading to neurogeneration and potential novel treatments"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["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","382"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Neuroendocrinology"],["dc.bibliographiccitation.lastpage","397"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Cardinali, Daniel P."],["dc.contributor.author","Hardeland, Rüdiger"],["dc.date.accessioned","2018-11-07T10:28:40Z"],["dc.date.available","2018-11-07T10:28:40Z"],["dc.date.issued","2017"],["dc.description.abstract","The metabolic syndrome (MS) is a collection of risk factors for cardiovascular disease, including obesity, hypertension, hyperinsulinemia, glucose intolerance and dyslipidemia. MS is associated with low-grade inflammation of the white adipose tissue, which can subsequently lead to insulin resistance, impaired glucose tolerance and diabetes. Adipocytes secrete proinflammatory cytokines as well as leptin and trigger a vicious circle which leads to additional weight gain largely as fat. The imbalance between inflammatory and anti-inflammatory signals is crucial to aging. Healthy aging can benefit from melatonin, a compound known to possess direct and indirect antioxidant properties, to have a significant protective effect on mitochondrial function, to enhance circadian rhythm amplitudes, to modulate the immune system and to exhibit neuroprotective actions. Melatonin levels decrease in the course of senescence and are more strongly reduced in diseases related to insulin resistance. This short review article analyzes the multiple protective actions of melatonin that are relevant to the attenuation of inflammatory responses and progression of inflammaging and how melatonin is effective to curtail MS in animal models of hyperadiposity. The clinical data supporting the possible therapeutic use of melatonin in human MS are also reviewed. Since attention has been focused on the development of potent melatonin analogs with prolonged effects (ramelteon, agomelatine, tasimelteon, piromelatine) and in clinical trials these analogs were administered in doses considerably higher than those usually employed for melatonin, clinical trials on melatonin in the range of 50-100 mg/day are needed to further assess its therapeutic value in MS. (C) 2016 S. Karger AG, Basel"],["dc.identifier.doi","10.1159/000446543"],["dc.identifier.isi","000398351400006"],["dc.identifier.pmid","27165273"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43476"],["dc.language.iso","en"],["dc.notes.intern","DeepGreen Import"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","S. Karger AG"],["dc.relation.eissn","1423-0194"],["dc.relation.issn","1423-0194"],["dc.relation.issn","0028-3835"],["dc.rights","https://www.karger.com/Services/SiteLicenses"],["dc.title","Inflammaging, Metabolic Syndrome and Melatonin: A Call for Treatment Studies"],["dc.type","journal_article"],["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","313"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","The International Journal of Biochemistry & Cell Biology"],["dc.bibliographiccitation.lastpage","316"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Pandi-Perumal, Seithikurippu R."],["dc.contributor.author","Cardinali, Daniel P."],["dc.date.accessioned","2018-11-07T10:12:39Z"],["dc.date.available","2018-11-07T10:12:39Z"],["dc.date.issued","2006"],["dc.description.abstract","Melatonin, originally discovered as a hormone of the pineal gland, is produced by bacteria, protozoa, plants, fungi, invertebrates, and various extrapineal sites of vertebrates, including out, skin, Harderian gland, and leukocytes. Biosynthetic pathways seem to be identical. Actions are pleiotropic, mediated by membrane and nuclear receptors, other binding sites or chemical interactions. Melatonin regulates the sleep/wake cycle, other circadian and seasonal rhythms, and acts as an immunostimulator and cytoprotective agent. Circulating melatonin is mostly 6-hydroxylated by hepatic P-450 monooxygenases and excreted as 6-sulfatoxymelatonin. Pyrrole-ring cleavage is of higher importance in other tissues, especially the brain. The product, N-1-acetyl-N-2-formyl-5-methoxykynuramine, is formed by enzymatic, pseudoenzymatic, photocatalytic, and numerous free-radical reactions. Additional metabolites result from hydroxylation and nitrosation. The secondary metabolite, N-1-acetyl-5-methoxykynuramine, supports mitochondrial function and downregulates cyclooxygenase 2. Antioxidative protection, safeguarding of mitochondrial electron flux, and in particular, neuroprotection, have been demonstrated in many experimental systems. Findings are encouraging to use melatonin as a sleep promoter and in preventing progression of neurodegenerative diseases. (C) 2005 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.biocel.2005.08.020"],["dc.identifier.isi","000234805700003"],["dc.identifier.pmid","16219483"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40280"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","1878-5875"],["dc.relation.issn","1357-2725"],["dc.title","Melatonin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]