The protection of bioenergetic functions in mitochondria by new synthetic chromanols.
alpha-Tocopherol is the most important lipophilic antioxidant of the chromanol type protecting biomembranes from lipid peroxidation (LPO). Therefore, alpha-tocopherol and its derivatives are frequently used in the therapy or prevention of oxygen radical-derived diseases. In the present study, novel chromanol-type antioxidants (twin-chromanol, cis- and trans-oxachromanol) as well as the well-known short-chain analogue of alpha-tocopherol, pentamethyl-chromanol, were tested for their antioxidative potency in rat heart mitochondria (RHM). Our experiments revealed that the bioenergetic parameters of mitochondria were not deteriorated in the presence of chromanols (up to 50 nmol/mg protein). Exposure of RHM to cumene hydroperoxide and Fe2+ (final concentrations 50 microM each), inducing LPO, significantly affected their bioenergetic parameters which were determined in the presence of glutamate and malate (substrates of mitochondrial complex I). Alterations of the bioenergetic parameters were partially prevented in a concentration-dependent manner by preincubating RHM with antioxidants before adding the radical-generating system. In the lower concentration range, twin-chromanol turned out to be more efficient than pentamethyl-chromanol, both being far more protective than cis- and trans-oxachromanol. Measurement of protein-bound SH groups and thiobarbituric acid-reactive substances revealed that this protective effect was due to their antioxidative action. Furthermore, HPLC measurements of alpha-tocopherol and alpha-tocopheryl quinone in rat liver mitochondria demonstrated an alpha-tocopherol-sparing effect of twin-chromanol. In conclusion, new chromanol-type antioxidants, especially twin-chromanol, were able to improve bioenergetic and biochemical parameters of mitochondria exposed to oxidative stress.
Staniek
Katrin
K
Research Institute for Biochemical Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210 Vienna, Austria.
Rosenau
Thomas
T
Gregor
Wolfgang
W
Nohl
Hans
H
Gille
Lars
L
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D002839:Chromans; D011506:Proteins; D013438:Sulfhydryl Compounds; D014810:Vitamin E; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman