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N-乙酰半胱氨酸调节多柔比星诱导的大鼠肝脏氧化应激和抗氧化维生素浓度。

N-acetylcysteine modulates doxorubicin-induced oxidative stress and antioxidant vitamin concentrations in liver of rats.

机构信息

Department of Internal Medicine, Division of Gastroenterology, Medical Faculty, Süleyman Demirel University, Isparta, Turkey.

出版信息

Cell Biochem Funct. 2010 Dec 2;28(8):673-7. doi: 10.1002/cbf.1707. Epub 2010 Nov 8.

Abstract

Doxorubicin (DOX) is a chemotherapeutic agent, and is widely used in cancer treatment. The most common side effect of DOX was indicated on cardiovascular system by experimental studies. There are some studies suggesting oxidative stress-induced toxic changes on liver related to DOX administration. The aim of the present study was to evaluate whether antioxidant N-acetylcysteine (NAC) relieves oxidative stress in DOX- induced liver injury in rat. Twenty-four male rats were equally divided into three groups. First group was used as a control. Second group received single dose of DOX. NAC for 10 days was given to constituting the third group after giving one dose of DOX. After 10 days of the experiment, liver tissues were taken from all animals. Lipid peroxidation (LP) levels were higher in the DOX group than in control whereas LP levels were lower in the DOX+NAC group than in control. Vitamin C and vitamin E levels were lower in the DOX group than in control whereas vitamin C and vitamin E levels were higher in the DOX+NAC group than in the DOX group. Reduced glutathione levels were higher in the DOX+NAC group than in control and DOX group. Glutathione peroxidase, vitamin A and β-carotene values were not changed in the three groups by DOX and NAC administrations. In histopathological evaluation of DOX group, there were mononuclear cell infiltrations, vacuolar degeneration, hepatocytes with basophilic nucleus and sinusoidal dilatations. The findings were totally recovered by NAC administration. In conclusion, N-acetylcysteine induced modulator effects on the doxorubicin-induced hepatoxicity by inhibiting free radical production and supporting the antioxidant vitamin levels.

摘要

多柔比星(DOX)是一种化疗药物,广泛用于癌症治疗。实验研究表明,DOX 最常见的副作用是对心血管系统的影响。有一些研究表明,DOX 给药会导致肝脏产生氧化应激诱导的毒性变化。本研究旨在评估抗氧化剂 N-乙酰半胱氨酸(NAC)是否能缓解 DOX 诱导的大鼠肝损伤中的氧化应激。将 24 只雄性大鼠等分为三组。第一组作为对照组。第二组给予 DOX 单剂量。第三组在给予 DOX 单剂量后给予 NAC 10 天。实验 10 天后,从所有动物中取出肝组织。与对照组相比,DOX 组的脂质过氧化(LP)水平更高,而 DOX+NAC 组的 LP 水平低于对照组。与对照组相比,DOX 组的维生素 C 和维生素 E 水平较低,而 DOX+NAC 组的维生素 C 和维生素 E 水平高于 DOX 组。DOX+NAC 组的还原型谷胱甘肽水平高于对照组和 DOX 组。DOX 和 NAC 给药后,三组的谷胱甘肽过氧化物酶、维生素 A 和β-胡萝卜素值均未发生变化。在 DOX 组的组织病理学评估中,存在单核细胞浸润、空泡变性、嗜碱性核肝细胞和窦扩张。NAC 给药完全恢复了这些发现。总之,N-乙酰半胱氨酸通过抑制自由基生成和支持抗氧化维生素水平,对 DOX 诱导的肝毒性产生了调节作用。

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