Gustafson D L, Swanson J D, Pritsos C A
Department of Nutrition and Cellular and Molecular Pharmacology, University of Nevada, Reno 89557.
Free Radic Res Commun. 1993;19(2):111-20. doi: 10.3109/10715769309056505.
The toxicity of the antineoplastic agent doxorubicin (DOX) has been shown to be moderated by the antioxidant enzyme glutathione peroxidase. It has been reported that acute doses of DOX can cause an inhibition of glutathione peroxidase in cardiac tissue, that may render this tissue especially susceptible to further prooxidant damage. In this study, multiple DOX treatments at a therapeutic dose were assessed for their effect on the antioxidant enzyme status of cardiac and kidney tissue. DOX was administered i.p. (5 mg/kg) once a week for two weeks to male balb/c mice. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPOX) and glutathione reductase (GR) were measured 1, 2 and 7 days following the second DOX treatment in both heart and kidney. Levels of reduced glutathione (GSH) were also measured in cardiac tissue at these same times. Cardiac levels of GPOX and GR showed a time-dependent decrease in activity, with 10% and 12% inhibition for GPOX and GR, respectively, at 7 days post second treatment. Cardiac levels of GSH also showed a significant decrease, approximately 15%, at 7 days post second treatment. Cardiac levels of SOD and CAT as well as kidney levels of all four antioxidant enzymes were not affected by DOX treatment. These data suggest that DOX given in a therapeutic regimen, at a therapeutic dose, can cause decreases in cardiac levels of GPOX, GR and GSH that could render the heart especially susceptible to further oxidative challenge.
抗肿瘤药物阿霉素（DOX）的毒性已被证明可被抗氧化酶谷胱甘肽过氧化物酶所减轻。据报道，急性剂量的DOX可导致心脏组织中谷胱甘肽过氧化物酶受到抑制，这可能使该组织特别容易受到进一步的促氧化损伤。在本研究中，评估了以治疗剂量多次给予DOX对心脏和肾脏组织抗氧化酶状态的影响。将DOX以5mg/kg的剂量腹腔注射给雄性balb/c小鼠，每周一次，共两周。在第二次给予DOX治疗后的第1、2和7天，测量心脏和肾脏中抗氧化酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPOX）和谷胱甘肽还原酶（GR）的活性。同时也在这些时间点测量心脏组织中还原型谷胱甘肽（GSH）的水平。心脏中GPOX和GR的活性呈现出时间依赖性降低，在第二次治疗后7天时，GPOX和GR的抑制率分别为10%和12%。心脏中GSH的水平在第二次治疗后7天也显著降低，约为15%。心脏中SOD和CAT的水平以及肾脏中所有四种抗氧化酶的水平均未受DOX治疗的影响。这些数据表明，以治疗方案给予治疗剂量的DOX可导致心脏中GPOX、GR和GSH水平降低，这可能使心脏特别容易受到进一步的氧化挑战。
