L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria
L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria
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DOI：
10.1002/ijc.20636
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发表时间：
2005-02-20
影响因子：
6.4
通讯作者：
Inoue, M
中科院分区：
文献类型：
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作者：
Chang, BJ;Nishikawa, M;Inoue, M
肝细胞癌通常先于慢性炎症。然而，肝癌发生的分子机制还不是很清楚。最近，我们报道了线粒体功能障碍通过产生自由基在肝癌的发生中起着重要作用。此外，我们还证明了L肉碱对体内线粒体功能的有效保护作用。因此，我们调查了长期服用L肉碱是否可以预防Long-Evans肉桂大鼠的肝炎和随后的肝细胞癌，Long-Evans Cinnamon大鼠经常被分析为肝癌发生的模型。结果表明，铜的异常堆积引起的氧化应激增加了游离脂肪酸的含量，从而导致线粒体功能障碍，导致细胞死亡，促进了活性氧的二次生成，而肉碱处理明显抑制了这一作用。最后，作为癌前病变标志物的胎盘谷胱甘肽-S转移酶阳性灶的出现和肝癌的发生被L肉碱显著抑制。这些事实表明，线粒体损伤在肝癌的发生发展中起着至关重要的作用，卡尼汀的临床应用对慢性肝炎患者具有很好的治疗潜力。(C)2004年Wiley-Liss公司
Hepatocellular carcinoma is usually preceded by chronic inflammation. However, the molecular mechanism in hepatocarcinogenesis is not well known. Recently, we reported that mitochondrial dysfunction plays an important role in hepatocarcinogenesis via the production of free radicals. Furthermore, we proved that L-carnitine effectively protects mitochondrial function in vivo. Therefore, we investigated whether long-term administration of L-carnitine could prevent hepatitis and subsequent hepatocellular carcinoma in Long-Evans Cinnamon rats that are often analyzed as a model of hepatocarcinogenesis. The results indicated that oxidative stress elicited from abnormally accumulated copper increased the amount of free fatty acids, thereby inducing mitochondrial dysfunction, resulting in cell death and enhanced secondary generation of reactive oxygen species, which were significantly inhibited by carnitine treatment. Finally, the occurrence of placental glutathione S-transferase-positive foci as a marker for pre-neoplastic lesions and hepatocarcinogenesis were significantly inhibited by L-carnitine. These facts suggest that mitochondrial injury plays an essential role in the development of hepatocarcinogenesis and that the clinical use of carnitine has excellent therapeutic potential in individuals with chronic hepatitis. (C) 2004 Wiley-Liss, Inc.