IDEBENONE PROTECTS HEPATIC MICROSOMES AGAINST OXYGEN RADICAL-MEDIATEDDAMAGE IN OXYGEN PRESERVATION SOLUTIONS

The ability of the benzoquinone coenzyme Q-10 or its derivative QSA-10 (idebenone) to protect against lipid peroxidation and protein damage mediated by the pro-oxidative system NADPH/ADP/Fe3+ was tested in a ra t liver microsomal model incubated in University of Wisconsin (UW) or histidine-tryptophan-ketoglutarate (HTK) solutions, Lipid peroxidation , as followed by direct determination of lipid hydroperoxides and by m onitoring of malondialdehyde equivalents, was 1.8-fold enhanced in HTK and 3-fold attenuated in UW compared with HEPES buffer, Function and integrity of microsomal enzymes were investigated using glutathione S- transferase and cytochrome P-450 IIIA activity as assessed by lidocain e N-deethylation to monoethylglycinexylidide as well as by Western blo t analysis of the cytochrome P-450 IIIA protein. Glutathione S-transfe rase activity was reduced by about 70% in HEPES compared with 50% in H TK and 36% in UW. Cytochrome P-450 IIIA was inactivated by about 75% i n HEPES and HTK, compared with 55% in UW. The enzyme inactivation was paralleled by a loss of immunoreactive cytochrome P-450 IIIA protein. Supplementation of HTK with 0.1 mu mol/L QSA-10 offered complete prote ction against lipid peroxidation, compared with 100 mu mol/L with Q-10 . QSA-10 (20 mu mol/L) prevented protein damage in both preservation s olutions, whereas Q-10 (20 mu moL/L) offered only partial protection i n UW and had no effect in HTK. The use of QSA-10 during liver transpla ntation may therefore have the potential of increasing the efficacy of organ preservation, maintaining donor organ quality, and preventing r eperfusion injury. It is suitable for human use and has energy-conserv ing properties in addition to its antioxidant nature.