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In vitro neuroprotection by novel antioxidants in guinea-pig urinary bladder subjected to anoxia-glucopenia/reperfusion damage.

Abstract
In a previous study, the neuroprotection provided by some hindered phenols of synthetic nature and alpha-tocopherol in guinea-pig detrusor strips subjected to ischaemia/reperfusion-like conditions was shown to be related directly to the antioxidant activity. The aim of the present study was to estimate the capability of three novel chimeric molecules derived by assembling known antioxidant moieties, namely FeAOX-6, comprising a chromanyl head and the polyisoprenyl sequence characteristic for lycopene, FeCD-52, derived from the conjugation of ascorbic acid and a polyphenol moiety (FeRS-4) and FeDG-17, derived from the combination of ascorbic acid and a chromanyl head, to confer neuroprotection in an in vitro model of guinea-pig whole urinary bladder subjected to anoxia-glucopenia/reperfusion injury. The antioxidant potential of these compounds was determined by oxygen radical absorbance capacity (ORAC) and phochemiluminescence (PCL) assays to test their peroxyl and anion superoxide (O2(*-)) radical trapping activity, respectively. FeAOX-6, FeCD-52 and FeDG-17 exerted both strong neuroprotective and antioxidant activity, significantly higher than those exerted by the individual component moieties. The antioxidant activity of FeCD-52 was 37-fold higher than that of the reference compound trolox. FeAOX-6 exerted remarkable neuroprotective activity, superior to that of FeCD-52 or FeDG-17, in spite of its lower antioxidant activity. These findings indicate that assembling antioxidant moieties yields neuroprotective agents, the effectiveness of which, however, is not related to the antioxidant activity. It is possible that a different partitioning in cell compartments critically involved in the oxidative damage pathway plays a role in neuroprotection exerted by these compounds.
AuthorsFederica Pessina, Katia Marazova, Paolino Ninfali, Luca Avanzi, Stefano Manfredini, Giampietro Sgaragli
JournalNaunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 370 Issue 6 Pg. 521-8 (Dec 2004) ISSN: 0028-1298 [Print] Germany
PMID15599711 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • Neuroprotective Agents
  • Glucose
Topics
  • Animals
  • Antioxidants (chemistry, pharmacology)
  • Dose-Response Relationship, Drug
  • Glucose (deficiency)
  • Guinea Pigs
  • Hypoxia (metabolism, prevention & control)
  • In Vitro Techniques
  • Male
  • Neuroprotective Agents (chemistry, pharmacology)
  • Reperfusion Injury (metabolism, prevention & control)
  • Urinary Bladder (drug effects, metabolism)

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