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富勒醇 C60(OH)24 在阿霉素处理的大鼠肾脏、睾丸和肺中的抗氧化特性。

Antioxidant properties of fullerenol C60(OH)24 in rat kidneys, testes, and lungs treated with doxorubicin.

机构信息

Medical Faculty, Department of Pharmacy, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, Serbia.

出版信息

Toxicol Mech Methods. 2010 Jul;20(6):298-305. doi: 10.3109/15376516.2010.485622.

Abstract

Clinical use of doxorubicin continues to be challenged by its undesirable systematic toxicity, caused mainly by oxidative stress. The aim of this study was to investigate the effectiveness of fullerenol C(60)(OH)(24) polyanion nanoparticles, an antioxidant agent, against doxorubicin-induced nephro-, testicular, and pulmonary toxicity. Results obtained in vitro suggest that fullerenol's anti-proliferative property and protective effect against doxorubicin cytotoxicity are mediated by the antioxidative and radical scavenging activity. Male Wistar rats were divided into five treatment groups: the control group (I) received 0.9% NaCl (1 mL/kg, i.p.). Groups II, III, IV, and V received a single dose of doxorubicin (10 mg/kg i.p.), doxorubicin/fullerenol (100 and 50 mg/kg i.p. of fullerenol 30 min prior to 10 mg/kg i.p. of doxorubicin), and fullerenol (100 mg/kg i.p.), respectively. On the 2(nd) and 14(th) days, organ samples were taken for the measurement of lipid peroxidation and activities of superoxide dismutase, catalase, glutathione-peroxidase, -reductase, and -transferase. Doxorubicin induced a significant increase of lipid peroxidation and alterations of antioxidant enzyme activities, while the fullerenol pre-treatment prevented the effects of doxorubicin on investigated parameters. Fullerenol, applied alone, did not alter basal values of the investigated animals. Considering the mechanisms of doxorubicin toxicity, it can be concluded that fullerenol exerts its protective role by acting as a free radical sponge and/or by removing free iron through formation of fullerenol-iron complex. Results of this study support the hypothesis of testicular, pulmo-, and nephroprotective efficacy of fullerenol in preventing oxidative stress induced by doxorubicin.

摘要

多柔比星的临床应用仍然受到其不良的系统毒性的挑战,主要是由氧化应激引起的。本研究旨在探讨富勒醇 C(60)(OH)(24)多阴离子纳米粒子作为一种抗氧化剂对多柔比星诱导的肾、睾丸和肺毒性的疗效。体外研究结果表明,富勒醇的抗增殖特性和对多柔比星细胞毒性的保护作用是通过抗氧化和自由基清除活性介导的。雄性 Wistar 大鼠分为五组:对照组(I)接受 0.9% NaCl(1 mL/kg,ip)。第 II、III、IV 和 V 组分别单次腹腔注射多柔比星(10 mg/kg)、多柔比星/富勒醇(30 分钟前给予 100 和 50 mg/kg 腹腔注射富勒醇,然后给予 10 mg/kg 腹腔注射多柔比星)和富勒醇(100 mg/kg,ip)。在第 2 天和第 14 天,取器官样本测量脂质过氧化和超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、-还原酶和 -转移酶的活性。多柔比星诱导脂质过氧化显著增加和抗氧化酶活性改变,而富勒醇预处理可防止多柔比星对所研究参数的影响。富勒醇单独应用不改变所研究动物的基础值。考虑到多柔比星毒性的机制,可以得出结论,富勒醇通过充当自由基海绵和/或通过形成富勒醇-铁络合物去除游离铁来发挥其保护作用。本研究结果支持富勒醇在预防多柔比星诱导的氧化应激方面具有睾丸、肺和肾保护作用的假说。

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