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硒代蛋氨酸对环磷酰胺毒性的血液保护作用。

Hematoprotective effect of seleno-L-methionine on cyclophosphamide toxicity in rats.

机构信息

Department of Biology, Faculty of Arts and Science, Eskisehir Osmangazi University, Eskisehir, Turkey.

出版信息

Drug Chem Toxicol. 2009;32(4):424-8. doi: 10.1080/01480540903130682.

DOI:10.1080/01480540903130682
PMID:19793036
Abstract

Cyclophosphamide (CP) is a widely used antineoplastic drug that causes toxicity in the normal cell due to its metabolites. The major drawback of this drug is an undesirable myelosuppression. Selenium (Se) is a potent nutritional antioxidant that carries out biological effects by its incorporation into selenoproteins, such as glutathione peroxidase (GPx). The possible protective effects of seleno-L-methionine (SLM) against CP-related toxicity of blood cells and bone marrow of rats were investigated in this study. Intraperitoneal (i.p) administration of 50, 100, or 150 mg/kg of CP caused, in a dose-dependent manner, reductions in the number of leukocytes (78, 89, and 92%, respectively), thrombocytes (22, 33, and 52%, respectively), and bone marrow-nucleated cells (72, 90, and 94%, respectively). The groups that had CP treatment alone were killed 3 days after the CP injection. For the groups having CP+SLM, SLM (0.4 or 0.8 mg/kg i.p) administration was started 3 days earlier than the CP administration and continued to the end of the experiment (6 days). On day 4, the animals were weighed again, relative doses of CP were estimated, and CP+SLM was administered together. On day 7, blood samples were collected and bone marrow of animals were resected under anesthesia. The results indicated that treatment of rats within a select dose range of SLM could reduce CP-induced toxicity on blood cells and bone marrow.

摘要

环磷酰胺(CP)是一种广泛使用的抗肿瘤药物,由于其代谢物会导致正常细胞中毒。这种药物的主要缺点是不可避免的骨髓抑制。硒(Se)是一种有效的营养抗氧化剂,通过将其掺入到硒蛋白中(如谷胱甘肽过氧化物酶(GPx))来发挥生物学作用。本研究旨在探讨硒代蛋氨酸(SLM)对 CP 相关的血细胞和骨髓毒性的可能保护作用。腹腔内(i.p)给予 50、100 或 150mg/kg 的 CP 会导致白细胞数量(分别为 78%、89%和 92%)、血小板(分别为 22%、33%和 52%)和骨髓有核细胞(分别为 72%、90%和 94%)呈剂量依赖性减少。单独接受 CP 治疗的组在 CP 注射后 3 天内被处死。对于接受 CP+SLM 的组,SLM(0.4 或 0.8mg/kg i.p)给药在 CP 给药前 3 天开始,并持续到实验结束(6 天)。第 4 天,再次称重动物,估计 CP 的相对剂量,并同时给予 CP+SLM。第 7 天,采集血液样本并在麻醉下切除动物的骨髓。结果表明,在 SLM 的选择剂量范围内治疗大鼠可降低 CP 诱导的血细胞和骨髓毒性。

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