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牛磺酸对甲氨蝶呤和他莫昔芬治疗的小鼠遗传毒性损伤的保护作用。

Protective role of taurine against genotoxic damage in mice treated with methotrexate and tamoxfine.

机构信息

Cell Biology Department, National Research Center, El Tahrir Street, 12622 Dokki, Giza, Egypt. dr

出版信息

Environ Toxicol Pharmacol. 2011 Jan;31(1):143-52. doi: 10.1016/j.etap.2010.10.001. Epub 2010 Oct 28.

Abstract

The genotoxic actions of anti-neoplastic drugs can lead to the development of secondary cancers in patients in extended remission. One of the most attractive approaches to disease prevention involves the use of natural antioxidants to protect tissue against toxic injury. We investigated the modulatory effects of exogenously administered taurine, on the genotoxicity of two well known anti-neoplastic drugs methotrexate (MTX) and tamoxifen (TAM) in Swiss albino mice. The animals were randomly divided into six groups consisting of ten mice each. Two groups were received single intraperitoneal injection of MTX (10 mg/kgb.wt.) and TAM (50 mg/kgb.wt.) to induce genotoxicity. Two other groups were treated orally with taurine (100 mg/kgb.wt.) for nine days prior to MTX and TAM administration. A vehicle treated control group and taurine control groups were also included. The protective effects of taurine were monitored by apoptosis assays and level of reduced glutathione (GSH), a key antioxidant, in liver, chromosomal aberrations in somatic and germ cells as well as sperm count, motility and morphology. The results indicated that taurine pre-treatment showed significant increment in the levels of GSH content, reduction in DNA fragmentation and ladder formation in hepatic tissue, suggesting the antioxidant activity of taurine may reduce the toxic effects of MTX and TAM. Treatment with taurine showed also significant reduction in the frequency of chromosomal aberrations in both somatic and germ cells. Moreover, it increases sperm count and motility, and decreases the incidence of sperm abnormalities. In conclusion, it appears that taurine protects against anti-neoplastic drugs-induced genotoxicity in somatic and germ tissues and may be of therapeutic potential in alleviating the risk of secondary tumors in chemotherapy.

摘要

抗肿瘤药物的遗传毒性作用可导致长期缓解的患者发生继发性癌症。预防疾病最有吸引力的方法之一是使用天然抗氧化剂来保护组织免受毒性损伤。我们研究了外源性牛磺酸对两种著名的抗肿瘤药物甲氨蝶呤(MTX)和他莫昔芬(TAM)在瑞士白化小鼠中的遗传毒性的调节作用。动物随机分为六组,每组 10 只。两组小鼠分别单次腹腔注射 MTX(10mg/kgb.wt.)和 TAM(50mg/kgb.wt.)以诱导遗传毒性。另外两组小鼠在 MTX 和 TAM 给药前连续 9 天口服牛磺酸(100mg/kgb.wt.)。还包括一个 vehicle 处理的对照组和一个牛磺酸对照组。通过凋亡检测和肝脏中还原型谷胱甘肽(GSH)的水平、体细胞和生殖细胞的染色体畸变以及精子计数、活力和形态来监测牛磺酸的保护作用。结果表明,牛磺酸预处理可显著增加 GSH 含量、减少肝组织中 DNA 片段化和梯状形成,表明牛磺酸的抗氧化活性可能减轻 MTX 和 TAM 的毒性作用。牛磺酸处理还显著降低了体细胞和生殖细胞中染色体畸变的频率。此外,它增加了精子计数和活力,并降低了精子异常的发生率。总之,牛磺酸似乎可以预防抗肿瘤药物引起的体细胞和生殖组织的遗传毒性,并可能具有减轻化疗中继发性肿瘤风险的治疗潜力。

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