Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection.
Administration of thymoquinone (10 mg kg(-1)day(-1), p.o.) with drinking water starting 5 days before a single injection of doxorubicin (15 mg kg(-1)i.p.) and continuing during the experimental period ameliorated the doxorubicin-induced cardiotoxicity in rats. This protection was evidenced from the significant reduction in serum enzymes: lactate dehydrogenase elevated level, 24 h and creatine phosphokinase elevated levels, 24 h and 48 h after doxorubicin administration. The cardiotoxicity of doxorubicin has been suggested to result from the generation of superoxide free-radical. The protective action of thymoquinone was examined against superoxide anion radical either generated photochemically, biochemically or derived from calcium ionophore (A23187) stimulated polymorphonuclear leukocytes. The results indicate that thymoquinone is a potent superoxide radical scavenger, scavenging power being as effective as superoxide dismutase against superoxide. In addition thymoquinone has an inhibitory effect on lipid peroxidation induced by Fe(3+)/ascorbate using rat heart homogenate. The superoxide scavenging and anti-lipid peroxidation may explain, in part, the protective effect of thymoquinone against doxorubicin-induced cardiotoxicity. 2000 Academic Press@p$hr
Nagi
M N
MN
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Mansour
M A
MA
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology*; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D004317:Doxorubicin / Q000009:adverse effects*; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005290:Ferric Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D013481:Superoxides / Q000378:metabolism
D016227:Benzoquinones; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D020011:Protective Agents; D013481:Superoxides; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; C003466:thymoquinone; D001205:Ascorbic Acid