Publications

Tamoxifen: Beyond the Antiestrogen Edited by J.A. Kellen Birkhäuser Verlay: Basel x+ 377 pages ISBN 3–7643–3842–3. 1996Free Radicals in Diagnostic Medicine A systems approach to Laboratory Technology, clinical correlations and antioxidant therapy Edited by D. Armstrong Plenum Press: New York. 1994. pp 464 ISBN 0–30644981–1Nitric Oxide and Radicals in the Pulmonary Vasculature Editors: Weir, K; Archer, S. L. and Reeves, J. T. Publisher: Futura Publishing Company, Inc. Armonk, NY Publication date: 1996Handbook of Antioxidants Cadenas E. Packer L (eds) Marcel Dekker Inc: New York. 1996. pp 602 ISBN 082479298-XTransgenic Organisms: Biological and Social Implications Edited by J Tomuik, K Wöhrmann and A Senther Birkhäuser Verlag, Easel, 1996

Abstract Background and objective Dementia, particularly Alzheimer’s disease, is a major healthcare challenge in ageing societies. Therefore, this study aimed to investigate the efficacy and safety of a dietary compound, ergothioneine, in delaying cognitive decline in elderly individuals. Design, intervention and measurements Nineteen subjects aged 60 or above with mild cognitive impairment were recruited for this double-blinded, randomized, and placebo- controlled study. Subjects received either ergothioneine (25mg per capsule) or a placebo, taken 3 times a week for one year. The whole blood profile, markers of renal and liver functions, neurocognitive performance, plasma levels of ergothioneine and its metabolites, and plasma biomarkers related to neurodegeneration were measured across the study. Result Ergothioneine intake did not alter clinical safety markers (blood counts, kidney and liver function) throughout the study, further validating its safety for human consumption. Subjects receiving ergothioneine demonstrated improved performance in assessment of learning ability and stabilized plasma levels of neurofilament light chain, compared with placebo group which saw no improvement in cognitive assessments and a significant increase in neurofilament light chain. Conclusion Prolonged intake of ergothioneine showed no toxicity in elderly individuals. Enhanced Rey Auditory Verbal Learning Test performance and stabilized neurofilament light chain levels suggest improvements in memory and learning abilities, alongside a deceleration of neuronal damage. Our results add to existing data that ergothioneine is safe for extended consumption and may hold the potential to delay cognitive decline in the elderly.

Hydroxytyrosol found in extra virgin olive oil strongly inhibited low-density lipoprotein oxidation stimulated by 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH), suggesting the ability to scavenge the AAPH-derived peroxyl radicals. Hydroxytyrosol inhibited iron-dependent phospholipid liposome peroxidation at low concentrations (IC50 = 50 ± 1.3 μM). In similar experiments, the calculated, IC50 values for other antioxidants compared are 1.5 ± 0.05 μM (carnosol), 2.25 ± 0.08 μM (carnosic acid), 65 ± 2.6 μM (Trolox C), and 250 ± 10 μM (vitamin E). Hydroxytyrosol and ascorbate reduced copper(II) ions to their copper(I) prooxidant form, but this was not reflected by their abilities to induce oxidative DNA damage in the complex copper−phenanthroline. Only high, nonphysiological, millimolar concentrations of pure hydroxytyrosol weakly stimulated copper-dependent chemical modification to DNA bases. The prooxidant (redox actions on metal ions) concentrations in vitro may never be achieved in vivo (following consumption of extra virgin olive oil). Thus, hydroxytyrosol may represent a useful diet-derived antioxidant depending on its bioavailability. Keywords: Extra virgin olive oil; hydroxytyrosol; low-density lipoprotein; rosemary; vitamin E; lipid peroxidation; plant antioxidants; DNA damage

Numerous studies have shown that postischemic myocardial dysfunction is attenuated by scavengers of hydroxyl ({sup {sm bullet}}OH) radicals and by iron chelators, suggesting an important pathogenetic role of {sup {sm bullet}}OH. However, the evidence provided by these studies is indirect. Since phenyl-alanine (PH) has been shown to react with {sup {sm bullet}}OH to form o-, m-, and p-tyrosines (TYR), the authors used aromatic hydroxylation of PH to detect {sup {sm bullet}}OH in stunned myocardium. Open-chest dogs underwent a 15-min coronary occlusion (O) followed by reperfusion (R). PH was infused i.v. starting 5 min pre-O and ending 10 min after R (n = 3) or starting at R and ending 10 min later (n = 8). TYR concentration in local coronary venous effluent plasma was measured using HPLC with electrochemical detection. No appreciable production of TYR was observed before or during O. After R, however, in all dogs there was a dramatic increase in myocardial production of o-, m-, and p-TYR which peaked at 1-3 min and ceased after 10 min. In 5 control dogs, infusion of PH without O/R did not result in any TYR production. These results provide evidence that the highly reactive {sup {sm bullet}}OH radical is producedmore » after brief regional ischemia in the intact animal and indicate that PH may be a useful probe for measuring this species. The findings support the hypothesis that {sup {sm bullet}}OH contributes to myocardial stunning.'« less