Horng Chi-Ting, Huang Chien-Wei, Yang Mon-Yuan, Chen Tzu-Hsin, Chang Yun-Ching, Wang Chau-Jong
Department of Ophthalmology, Kaohsiung Armed Forces General Hospital, Kaohsiung City, 802, Taiwan.
Institute of Biochemistry, Microbiology and Immunology, Medical College, Chung Shan Medical University, Taichung City, 402, Taiwan.
Environ Toxicol. 2017 Nov;32(11):2327-2340. doi: 10.1002/tox.22434. Epub 2017 Aug 14.
Lotus (Nelumbo nucifera Gaertn) possesses antioxidant, hepatoprotective, and anticancer potential. This study determined the protective role of aqueous extract from Nelumbo nucifera leaves (NLE) against N-diethylnitrosamine (DEN)-induced oxidative stress and hepatocellular carcinogenesis in a sample of Sprague-Dawley rats. NLE was fed orally to rats in which hepatic carcinoma was induced with DEN for 12 weeks. Five groups of 12 rats each were used for the study: Group I (control group) rats received distilled water; Group II rats were induced with DEN; Group III rats were induced with DEN and cotreated with 0.5% NLE; Group IV rats were induced with DEN and cotreated with 1.0% NLE; and Group V rats were induced with DEN and cotreated with 2.0% NLE. Clinical chemistry, organ weight, inflammatory marker, protein expression, enzyme, and antioxidant analyses were conducted. NLE administration to rats resulted in significantly decreased levels of serum alanine aminotransferase, aspartate aminotransferase, and albumin, which is indicative of hepatocellular damage, compared with the control group. DEN-induced oxidative stress was inhibited by NLE and this inhibition was paralleled by decreased lipid peroxides and increased glutathione transferase, superoxide dismutase, catalase, and glutathione peroxidase activity in liver tissues. The status of nonenzymatic antioxidants, such as reduced glutathione, was also found to be increased in NLE-administered rats. Furthermore, NLE decreased tumor size, hepatic Rac1, PKCα, and GSTπ expressions compared with the DEN-only group. Thus, supplementation of NLE reduced the adverse changes that occur because of liver cancer. These results prove that NLE protects against liver carcinogenesis induced because of treatment with DEN through blocking lipid peroxidation, hepatic cell damage, and enhancing the antioxidant defense system.
莲花（莲）具有抗氧化、保肝和抗癌潜力。本研究确定了莲叶水提取物（NLE）对N-二乙基亚硝胺（DEN）诱导的Sprague-Dawley大鼠氧化应激和肝细胞癌发生的保护作用。将NLE口服给予用DEN诱导肝癌12周的大鼠。每组12只大鼠，共五组用于该研究：第一组（对照组）大鼠接受蒸馏水；第二组大鼠用DEN诱导；第三组大鼠用DEN诱导并同时用0.5%NLE处理；第四组大鼠用DEN诱导并同时用1.0%NLE处理；第五组大鼠用DEN诱导并同时用2.0%NLE处理。进行了临床化学、器官重量、炎症标志物、蛋白质表达、酶和抗氧化分析。与对照组相比，给大鼠施用NLE导致血清丙氨酸转氨酶、天冬氨酸转氨酶和白蛋白水平显著降低，这表明肝细胞受到损伤。NLE抑制了DEN诱导的氧化应激，这种抑制伴随着肝组织中脂质过氧化物减少以及谷胱甘肽转移酶、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性增加。还发现，在施用NLE的大鼠中，非酶抗氧化剂如还原型谷胱甘肽的状态也有所增加。此外，与仅用DEN处理的组相比，NLE减小了肿瘤大小，降低了肝脏Rac1、PKCα和GSTπ的表达。因此，补充NLE减少了因肝癌而发生的不良变化。这些结果证明，NLE通过阻断脂质过氧化、肝细胞损伤以及增强抗氧化防御系统，对DEN治疗诱导的肝癌具有保护作用。
