Derivatised alpha-tocopherol as a CoQ10 carrier in a novel water-soluble formulation.
We have derivatised alpha-tocopherol (vitamin E) to a water-soluble polyoxyethanyl-alpha - tocopheryl sebacate (PTS) and discovered that it formed a non-covalent complex with CoQ10 at a molar ratio of 2:1 (PTS-CoQ10). 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 CoQ10 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-CoQ10 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.
Sikorska
Marianna
M
Neurobiology Program, Institute for Biological Sciences, National Research Council of Canada, Ottawa, K1A 0R6, ON, Canada. marianna.sikorska@nrc.ca
Borowy-Borowski
Henryk
H
Zurakowski
Bogdan
B
Walker
P Roy
PR
D000085:Acetates; D000473:Alkanes / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001682:Biological Availability; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D003067:Coenzymes; D005021:Ethylamines / Q000737:chemistry; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000737:chemistry; D016548:Prosencephalon; D051381:Rats; D017207:Rats, Sprague-Dawley; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics
D000085:Acetates; D000473:Alkanes; D000975:Antioxidants; D003067:Coenzymes; D005021:Ethylamines; D018696:Neuroprotective Agents; C482379:polyoxyethanyl-alpha-tocopheryl sebacate; C061659:sebacoyl chloride; D014451:Ubiquinone; D011092:Polyethylene Glycols; C007650:ethyl acetate; C024989:coenzyme Q10; D024502:alpha-Tocopherol; C016162:triethylamine