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慢性阿霉素治疗对雄性和雌性大鼠心脏、肾脏及肝脏组织的影响。

The effect of chronic adriamycin treatment on heart kidney and liver tissue of male and female rat.

作者信息

Julicher R H, Sterrenberg L, Haenen G R, Bast A, Noordhoek J

机构信息

Ministry of Agriculture and Fisheries, Den Haag, The Netherlands.

出版信息

Arch Toxicol. 1988;61(4):275-81. doi: 10.1007/BF00364850.

Abstract

The influence of chronic adriamycin treatment on cellular defence mechanisms against free radicals has been determined in rats. To that end, the changes in vitamin E content, activity of superoxide dismutase, catalase and factors of the glutathione system were measured in heart, kidneys and liver after 24 and 52 days of treatment. Moreover, damage was assessed by measuring the activity of NADPH- and NADH-cytochrome c reductase. The results concerning the components of the oxidative defence systems in male rats showed reductions in the activity of superoxide dismutase and catalase in renal tissue and in factors of the glutathione system in liver tissue. In cardiac tissue an increased activity of catalase and elevated content of total glutathione were found. Vitamin E content was increased in liver and to a lesser extent, in kidneys. The activity of Se-dependent glutathione peroxidase sharply decreased only in liver. Major differences between male and female rats were not observed in renal and cardiac tissue, as far as protective factors were concerned. However, a decrease in catalase activity was detectable earlier in male kidneys. The protective factors in liver of female rats were far less susceptible to in vivo treatment with adriamycin, as compared to liver of male rats. Decreased activity of the cytochrome reductases was found in liver of male rats. In male renal tissue only cytochrome c reductase activity was significantly reduced. Male cardiac tissue showed no signs of biochemical damage, although from histological examination in a parallel study [J Natl Cancer Inst 76: 299-307 (1986)] lesions were evident. In female rats no damage was found in liver, kidneys and heart.

摘要

已在大鼠中确定了慢性阿霉素治疗对细胞自由基防御机制的影响。为此,在治疗24天和52天后,测量了心脏、肾脏和肝脏中维生素E含量、超氧化物歧化酶、过氧化氢酶活性以及谷胱甘肽系统的相关因子。此外,通过测量NADPH-和NADH-细胞色素c还原酶的活性来评估损伤情况。雄性大鼠氧化防御系统各组分的结果显示,肾组织中超氧化物歧化酶和过氧化氢酶活性降低,肝组织中谷胱甘肽系统的相关因子降低。在心脏组织中,过氧化氢酶活性增加,总谷胱甘肽含量升高。肝脏中维生素E含量增加,肾脏中增加程度较小。仅肝脏中硒依赖性谷胱甘肽过氧化物酶的活性急剧下降。就保护因子而言,在肾脏和心脏组织中未观察到雄性和雌性大鼠之间的主要差异。然而,雄性肾脏中过氧化氢酶活性的降低在更早阶段就可检测到。与雄性大鼠的肝脏相比,雌性大鼠肝脏中的保护因子对阿霉素体内治疗的敏感性要低得多。在雄性大鼠的肝脏中发现细胞色素还原酶活性降低。在雄性肾组织中,仅细胞色素c还原酶活性显著降低。雄性心脏组织未显示生化损伤迹象,尽管在一项平行研究的组织学检查中[《美国国家癌症研究所杂志》76: 299 - 307 (1986)]病变明显。在雌性大鼠中,肝脏、肾脏和心脏均未发现损伤。

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