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阿拉伯胶树树皮中的多酚类物质对N-亚硝基二乙胺诱导的肝癌发生的潜在化学预防作用

Potential chemoprevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by polyphenolics from Acacia nilotica bark.

作者信息

Singh Brahma N, Singh Braj R, Sarma B K, Singh H B

机构信息

Department of Mycology and Plant Pathology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

出版信息

Chem Biol Interact. 2009 Sep 14;181(1):20-8. doi: 10.1016/j.cbi.2009.05.007. Epub 2009 May 14.

DOI:10.1016/j.cbi.2009.05.007
PMID:19446540
Abstract

Chemopreventive potential of Acacia nilotica bark extract (ANBE) against single intraperitoneal injection of N-nitrosodiethylamine (NDEA, 200mg/kg) followed by weekly subcutaneous injections of carbon tetrachloride (CCl(4), 3 ml/kg) for 6 weeks induced hepatocellular carcinoma (HCC) in rats was studied. At 45 day after administration of NDEA, 100 and 200mg/kg of ANBE were administered orally once daily for 10 weeks. The levels of liver injury and liver cancer markers such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (gamma-GT), total bilirubin level (TBL), alpha-feto protein (AFP) and carcinoembryonic antigen (CEA) were substantially increased following NDEA treatment. However, ANBE treatment reduced liver injury and restored liver cancer markers. ANBE also significantly prevented hepatic malondialdehyde (MDA) formation and reduced glutathione (GSH) in NDEA-treated rats which was dose dependent. Additionally, ANBE also increased the activities of antioxidant enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) in the liver of NDEA-administered rats. Eventually, ANBE also significantly improved body weight and prevented increase of relative liver weight due to NDEA treatment. Histological observations of liver tissues too correlated with the biochemical observations. HPLC analysis of ANBE showed the presence of gallic, protocatechuic, caffeic and ellagic acids, and also quercetin in ANBE. The results strongly support that A. nilotica bark prevents lipid peroxidation (LPO) and promote the enzymatic and non-enzymatic antioxidant defense system during NDEA-induced hepatocarcinogenesis which might be due to activities like scavenging of oxy radicals by the phytomolecules in ANBE.

摘要

研究了阿拉伯胶树树皮提取物(ANBE)对大鼠肝细胞癌(HCC)的化学预防潜力。通过单次腹腔注射N-亚硝基二乙胺(NDEA,200mg/kg),随后每周皮下注射四氯化碳(CCl₄,3ml/kg),持续6周诱导大鼠发生肝细胞癌。在给予NDEA后45天,以100mg/kg和200mg/kg的ANBE每日口服一次,持续10周。NDEA处理后,肝损伤和肝癌标志物如丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、γ-谷氨酰转移酶(γ-GT)、总胆红素水平(TBL)、甲胎蛋白(AFP)和癌胚抗原(CEA)的水平显著升高。然而,ANBE处理减轻了肝损伤并恢复了肝癌标志物。ANBE还显著预防了NDEA处理大鼠肝脏中丙二醛(MDA)的形成,并降低了谷胱甘肽(GSH),且具有剂量依赖性。此外,ANBE还增加了NDEA给药大鼠肝脏中抗氧化酶即过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)和谷胱甘肽-S-转移酶(GST)的活性。最终,ANBE还显著改善了体重,并防止了因NDEA处理导致的相对肝脏重量增加。肝脏组织的组织学观察结果也与生化观察结果相关。ANBE的高效液相色谱分析表明,ANBE中存在没食子酸、原儿茶酸、咖啡酸和鞣花酸,以及槲皮素。结果有力地支持了阿拉伯胶树树皮在NDEA诱导的肝癌发生过程中可预防脂质过氧化(LPO)并促进酶促和非酶促抗氧化防御系统,这可能归因于ANBE中植物分子清除氧自由基等活性。

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