α-Tocopherol mediated amelioration of camptothecin-induced free radical damage to avert cardiotoxicities.
Hum Exp Toxicol. 2015 Apr ;34(4):380-9. Epub 2014 Oct 10. PMID: 25304969
Reactive oxygen species (ROS) such as O2(-), hydrogen peroxide, and OH(-) are highly toxic to cells. Cellular antioxidant enzymes and free radical scavengers normally protect a cell from toxic effects of ROS. However, when generation of ROS overtakes the antioxidant defense of the cells, it leads to various pathological conditions. The present study investigated the protective efficacy ofα-tocopherol on the peroxidative damage and abnormal antioxidant levels in the myocardial tissue of camptothecin (CPT), administered at the dosage of 6 mg/kg/day in male Wistar rats. CPT-administered rats showed significant increase (p<0.001) in lipid peroxidation and abnormal changes in the activities/levels of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione S-transferase) and nonenzymic antioxidants (reduced glutathione and vitamin E). Alterations in the levels of tissue alkaline phosphatase, lactate dehydrogenase (p<0.01), alanine transaminase (p<0.001), and aspartate transaminase (p<0.001) were also observed in CPT-treated rats. In contrast, rats pretreated withα-tocopherol showed significant revision of elevated levels of lipid peroxides and abnormal antioxidant enzyme activity suggesting the ameliorative property of vitamin E. Histopathological alterations in the heart tissue observed after CPT administration were also protected in animals that were pretreated with vitamin E. Based on our results, we conclude that supplementation of vitamin E may improve the efficacy of standard and experimental cancer therapies by subsiding the toxic effect of the antineoplastic agent.