Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas
Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas
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DOI：
10.1016/j.biomaterials.2008.04.048
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发表时间：
2008-08-01
期刊：
影响因子：
14
通讯作者：
Strukelj, Borut
中科院分区：
文献类型：
--
作者：
Injac, Rade;Perse, Martina;Strukelj, Borut
本研究的目的是使用体内（雌性Sprague-Dawley大鼠）和体外（人肝细胞癌-HepG 2;结肠直肠腺癌细胞系- Caco-2）方法研究富勒烯醇C-60（OH）（24）对阿霉素诱导的肝毒性的潜在保护作用。第一组（健康对照组）和第二组（化学诱导乳腺癌对照组）仅接受生理盐水。第三、第四和第五组（均患有乳腺癌）分别注射（i. p.）分别给予单剂量的多柔比星（8 mg/kg）、多柔比星/富勒烯醇（在给予8 mg/kg多柔比星之前30分钟给予100 mg/kg富勒烯醇）和富勒烯醇（100 mg/kg）。处理后两天，处死大鼠。结果表明，阿霉素单独治疗引起血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）和α-羟基丁酸脱氢酶（α-hydroxybutyrate dehydrogenase，α-LDH）水平的显著变化（α-HBDH），以及丙二醛（MDA）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-Px）、总抗氧化状态（TAS）、谷胱甘肽还原酶（GR），过氧化氢酶（CAT）和超氧化物歧化酶（SOD）。这些影响显着减少所有的研究参数，但不为MDA和GSH水平的预处理富勒烯。用浓度为10 μ g/mL和44 μ g/mL的富勒烯醇连续处理HepG 2和Caco-2细胞系12 h、24 h、48 h和96 h。为了评价富勒醇对阿霉素诱导的肝毒性的调节活性，用阿霉素（1 μ M; 5 μ M）和富勒醇（10 μ g/mL：44 μ g/mL）以不同的组合同时处理细胞系。当用5 μ M阿霉素沿着富勒烯醇处理细胞时，我们可以看到在整个时间线内细胞性能的显著改善。我们可以得出结论，富勒醇本身对HepG 2具有细胞毒性作用，但当氧化应激过高时，富勒醇的细胞毒性作用被其作为强抗氧化剂化合物的保护作用所克服。(c)2008爱思唯尔有限公司保留所有权利。
The aim of this study was to investigate the potential protective role of fullerenol C-60(OH)(24) on doxorubicin-induced liver toxicity using in vivo (female Sprague-Dawley rats) and in vitro (human hepatocellular carcinoma - HepG2; colorectal adenocarcinoma cell lines - Caco-2) approaches. The first (healthy control) and second (control with chemically induced mammary carcinomas) group received saline only. The third, fourth and fifth group (all with breast cancer) were injected (i.p.) with a single dose of doxorubicin (8 mg/kg), doxorubicin/fullerenol (100 mg/kg of fullerenol 30 min before administration of 8 mg/kg doxorubicin) and fullerenol (100 mg/kg), respectively. Two days after treatment, the rats were sacrificed. Results showed that treatment with doxorubicin alone caused significant changes in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), as well as in the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) in the liver tissue. These effects were significantly reduced for all investigated parameters by pre-treatment with fullerenol but not for the MDA and GSH level. The HepG2 and Caco-2 cell lines were continuously treated with fullerenol for 12 h, 24 h, 48 h and 96 h at concentrations of 10 mu g/mL and 44 mu g/mL. With the aim of evaluating the modulating activity of fullerenol on doxorubicin-induced hepatotoxicity, the cell lines were simultaneously treated with doxorubicin (1 mu M; 5 mu M) and fullerenol (10 mu g/mL: 44 mu g/mL) in different combinations. When the cells are treated with 5 mu M doxorubicin along with the fullerenol, we can see a significant improvement of the cell capability during the entire time-line. We can conclude that fullerenol has cytotoxic effects on HepG2 by itself, but when the oxidative stress is too high the cytotoxic effects of fullerenol are overcome by its protective role as a strong antioxidant compound. (c) 2008 Elsevier Ltd. All rights reserved.