ROLE OF ASCORBATE IN PROTECTION BY NITECAPONE AGAINST CARDIAC ISCHEMIA-REPERFUSION INJURY

被引:22
作者
HARAMAKI, N [1 ]
STEWART, DB [1 ]
AGGARWAL, S [1 ]
KAWABATA, T [1 ]
PACKER, L [1 ]
机构
[1] UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,MEMBRANE BIOENERGET GRP,BERKELEY,CA 94720
关键词
RAT HEART; MYOCARDIAL ANTIOXIDANT; ASCORBATE; IRON CHELATION;
D O I
10.1016/0006-2952(95)00208-H
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The antioxidant properties of nitecapone, a catechol derivative and an inhibitor of catechol-O-methyltransferase, were reported recently. In the present study, the influence of nitecapone on isolated rat heart ischemia-reperfusion injury was investigated to elucidate its cardioprotective role. Nitecapone, administered in the perfusion buffer from the beginning of the pre-ischemic phase, significantly improved recovery of cardiac mechanical function, suppressed enzyme leakage in the coronary effluent, and minimized loss of ascorbate, compared with the control group. In rats fed a diet containing 4% ascorbate, myocardial ascorbate content in ascorbate-fed rats after ischemia-reperfusion was higher than that in control rats fed a normal diet without ischemia. However, supplemented rats did not show any beneficial effects on cardiac mechanical recovery or enzyme leakage, suggesting that maintenance of tissue ascorbate level is not the cause, but the result of the protective effects of nitecapone against cardiac ischemia-reperfusion injury. The iron-chelating effect of nitecapone was also tested. It was confirmed, using electron spin resonance, that 50 mu M nitecapone chelates the same concentration of iron released from the heart into the coronary effluent. Hence, the iron-chelating ability of nitecapone may be responsible, at least in part, for its cardioprotective effects in ischemia-reperfusion injury.
引用
收藏
页码:839 / 843
页数:5
相关论文
共 28 条
  • [1] DETECTION OF FERRYL MYOGLOBIN IN THE ISOLATED ISCHEMIC RAT-HEART
    ARDUINI, A
    EDDY, L
    HOCHSTEIN, P
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1990, 9 (06) : 511 - 513
  • [2] THE IRON CHELATOR DESFERRIOXAMINE ATTENUATES POSTISCHEMIC VENTRICULAR DYSFUNCTION
    BOLLI, R
    PATEL, BS
    ZHU, WX
    ONEILL, PG
    HARTLEY, CJ
    CHARLAT, ML
    ROBERTS, R
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1987, 253 (06): : H1372 - H1380
  • [3] FREE-RADICALS AND CARDIOPLEGIA - ORGANIC ANTI-OXIDANTS AS ADDITIVES TO THE ST-THOMAS-HOSPITAL CARDIOPLEGIC SOLUTION
    CHAMBERS, DJ
    ASTRAS, G
    TAKAHASHI, A
    MANNING, AS
    BRAIMBRIDGE, MV
    HEARSE, DJ
    [J]. CARDIOVASCULAR RESEARCH, 1989, 23 (04) : 351 - 358
  • [4] COPPER AND IRON ARE MOBILIZED FOLLOWING MYOCARDIAL-ISCHEMIA - POSSIBLE PREDICTIVE CRITERIA FOR TISSUE-INJURY
    CHEVION, M
    JIANG, YD
    HAREL, R
    BERENSHTEIN, E
    URETZKY, G
    KITROSSKY, N
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (03) : 1102 - 1106
  • [5] DETERMINATION OF DEHYDROASCORBIC ACID USING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH COULOMETRIC ELECTROCHEMICAL DETECTION
    DHARIWAL, KR
    WASHKO, PW
    LEVINE, M
    [J]. ANALYTICAL BIOCHEMISTRY, 1990, 189 (01) : 18 - 23
  • [6] DUNPHY G, 1990, CLIN CHEM, V36, P778
  • [7] ROLE OF OXYGEN RADICALS IN MYOCARDIAL REPERFUSION INJURY - EXPERIMENTAL AND CLINICAL-EVIDENCE
    FLAHERTY, JT
    ZWEIER, JL
    [J]. KLINISCHE WOCHENSCHRIFT, 1991, 69 (21-23): : 1061 - 1065
  • [8] CARDIAC REPERFUSION DAMAGE PREVENTED BY A NITROXIDE FREE-RADICAL
    GELVAN, D
    SALTMAN, P
    POWELL, SR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (11) : 4680 - 4684
  • [9] EFFECTS OF NATURAL ANTIOXIDANT GINKGO-BILOBA EXTRACT (EGB-761) ON MYOCARDIAL ISCHEMIA-REPERFUSION INJURY
    HARAMAKI, N
    AGGARWAL, S
    KAWABATA, T
    DROYLEFAIX, MTT
    PACKER, L
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1994, 16 (06) : 789 - 794
  • [10] DELETERIOUS EFFECTS OF OXYGEN RADICALS IN ISCHEMIA REPERFUSION - RESOLVED AND UNRESOLVED ISSUES
    KLONER, RA
    PRZYKLENK, K
    WHITTAKER, P
    [J]. CIRCULATION, 1989, 80 (05) : 1115 - 1127