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N-乙酰半胱氨酸对大鼠辐射诱导的DNA损伤和肝毒性的保护作用。

Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats.

作者信息

Mansour Heba H, Hafez Hafez F, Fahmy Nadia M, Hanafi Nemat

机构信息

Health Radiation Research Department, National Center for Radiation Research and Technology, Nasr City, Cairo, Egypt.

出版信息

Biochem Pharmacol. 2008 Feb 1;75(3):773-80. doi: 10.1016/j.bcp.2007.09.018. Epub 2007 Sep 25.

DOI:10.1016/j.bcp.2007.09.018
PMID:18028880
Abstract

The present study was designed to evaluate the radioprotective effect of N- acetylcysteine (NAC) on gamma-radiation induced toxicity in hepatic tissue in rat. The cellular changes were estimated using malondialdehyde (MDA, an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), reduced glutathione (GSH), and total nitrate/nitrite (NO(x)) as markers of hepatic oxidative stress in rats following gamma-irradiation. The DNA damage was determined by agarose gel electrophoresis. To achieve the ultimate goal of this study, 40 adult rats were randomly divided into 4 groups of 10 animals each. Group I was injected intraperitoneally with saline solution for 7 consecutive days and served as control group. Group II was irradiated with a single dose of 6Gy gamma-radiation. Group III was daily injected with NAC (1g/kg, i.p.) for 7 consecutive days. Group IV received a daily i.p. injection of NAC (1g/kg, i.p.) for 7 consecutive days and 1h after the last dose, rats were irradiated with a single dose (6Gy) gamma-radiation. The animals were sacrificed after 24h. DNA damage was observed in tissue after total body irradiation with a single dose of 6Gy. Malondialdehyde and total nitrate/nitrite were increased significantly whereas the levels of GSH and antioxidant enzymes were significantly decreased in gamma-irradiated group. Pretreatment with NAC showed a significant decrease in the levels of MDA, NO(x) and DNA damage. The antioxidant enzymes increased significantly along with the levels of GSH. Moreover, histopathological examination of liver tissues confirmed the biochemical data. Thus, our results show that pretreatment with N-acetylcysteine offers protection against gamma-radiation induced cellular damage.

摘要

本研究旨在评估N-乙酰半胱氨酸(NAC)对大鼠肝脏组织中γ射线诱导的毒性的辐射防护作用。使用丙二醛(MDA,脂质过氧化指标)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)、还原型谷胱甘肽(GSH)和总硝酸盐/亚硝酸盐(NO(x))作为γ射线照射后大鼠肝脏氧化应激的标志物来评估细胞变化。通过琼脂糖凝胶电泳测定DNA损伤。为实现本研究的最终目标,将40只成年大鼠随机分为4组,每组10只动物。第一组连续7天腹腔注射生理盐水作为对照组。第二组接受单次6Gyγ射线照射。第三组连续7天每日腹腔注射NAC(1g/kg,腹腔注射)。第四组连续7天每日腹腔注射NAC(1g/kg,腹腔注射),在最后一剂后1小时,大鼠接受单次(6Gy)γ射线照射。24小时后处死动物。单剂量6Gy全身照射后组织中观察到DNA损伤。γ射线照射组中丙二醛和总硝酸盐/亚硝酸盐显著增加,而GSH和抗氧化酶水平显著降低。NAC预处理显示MDA、NO(x)水平和DNA损伤显著降低。抗氧化酶以及GSH水平显著增加。此外,肝脏组织的组织病理学检查证实了生化数据。因此,我们的结果表明,N-乙酰半胱氨酸预处理可提供针对γ射线诱导的细胞损伤的保护作用。

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