Affiliations: Neurobiology Program, Institute for Biological
Sciences, National Research Council of Canada, Ottawa, K1A 0R6, ON,
Canada
Note: [] Address for correspondence: Dr. Marianna Sikorska, Institute for
Biological Sciences, National Research Council of Canada, 1200 Montreal Road,
Bldg. M-54, Ottawa, ON K1A 0R6, Canada. Tel.: +1 613 993 5916; Fax: +1 613 990
7963; E-mail: marianna.sikorska@nrc.ca
Abstract: We have derivatised α-tocopherol (vitamin E)
to a water-soluble polyoxyethanyl-α – tocopheryl
sebacate (PTS) and discovered that it formed a non-covalent complex with
CoQ_{10} at a molar ratio of 2:1
(PTS-CoQ_{10}). This complex was water-soluble and remained
stable for extended periods of time. After oral delivery of the formulation
into rats PTS was hydrolysed to vitamin E and elevated levels of both vitamin E
and CoQ_{10} in blood plasma were detected within 1 h. Thus,
this aqueous formulation contains a combination of two potent antioxidants. The
formulation's efficacy was tested against ischemic brain damage caused by a
transient (8~min) bilateral occlusion of the common carotid arteries in rats.
The animals received PTS-CoQ_{10} by two intraperitoneal
injections given immediately after ischemia and 3~h later and the brain damage
was assessed up to 12 days post-ischemia. A significant neuroprotection was
observed in the CA1 hippocampal region, for example at 12 days approximately
50% of CA1 neurons were still alive in the treated animals versus less than
5% in the non-treated group. Our data is consistent with previously published
observations indicating the therapeutic potential of antioxidants for
treatments of ischemia/reperfusion injuries and the formulation described here
is particularly appropriate for the application in acute conditions, such as
stroke or cardiac arrest.
Keywords: neuroprotection, coenzyme Q[TeX:] _{10}, vitamin E, antioxidants, ischemia, reperfusion
Journal: BioFactors, vol. 18, no. 1-4, pp. 173-183, 2003
