Echinochrome, a naturally occurring iron chelator and free radical scavenger in artificial and natural membrane systems.
Echinochrome, or 6-ethyl-2,3,5,7,8-pentahydroxy-1,4-naphthoquinone, possesses cardioprotective activity, and diminishes the myocardial ischemia/reperfusion injury that is known to be accompanied by free-radical oxidative damage and calcium overload. In this study, we investigated the lipophilicity of echinochrome, its ability to inhibit free-radical oxidation both in the bulk organic phase and in an artificial membrane system (liposomes), and to prevent the ferrous/ascorbate-induced leakage of calcium from the isolated sarcoplasmic reticulum (SR) of rabbit skeletal muscle. The experimentally-determined octanol/water partition coefficient (LogP) of echinochrome was +3.11, and the distribution coefficient (LogD) was +2.58 at pH 6.0 and -0.15 at pH 8.0. Echinochrome displayed high scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals with a stoichiometry of about 1:7. Echinochrome was more effective in inhibiting the phosphatidyl choline liposome peroxidation induced by Fe2+/ascorbate than that induced by hemin. The iron chelating ability of echinochrome was estimated spectrophotometrically. In isolated SR, echinochrome protected the ATP-dependent Ca2+-pump system from damage by Fe2+/ascorbate. It was concluded that iron chelation predominates in the overall antioxidant potential of echinochrome.
Lebedev
Alexander V
AV
Institute of Experimental Cardiology, Cardiology Research Center, Russian Ministry of Health, 3rd Cherepkovskaya ul. 15a, Moscow, 112552 Russia. avleb@cardio.ru
Ivanova
Marina V
MV
Levitsky
Dmitri O
DO
D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D006834:Hydrazines / Q000378:metabolism; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D000442:Octanols / Q000737:chemistry; D010084:Oxidation-Reduction; D010851:Picrates; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D006834:Hydrazines; D007502:Iron Chelating Agents; D008081:Liposomes; D009285:Naphthoquinones; D000442:Octanols; D010851:Picrates; D012997:Solvents; D014867:Water; C004931:1,1-diphenyl-2-picrylhydrazyl; C007573:echinochrome A; D002118:Calcium