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