Amereh Zahra, Hatami Nasrin, Shirazi Farshad H, Gholami Saman, Hosseini Seyed Hojjat, Noubarani Maryam, Kamalinejad Mohammad, Andalib Sina, Keyhanfar Fariborz, Eskandari Mohammad Reza
Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
EXCLI J. 2017 Jul 18;16:1046-1056. doi: 10.17179/excli2017-389. eCollection 2017.
Hepatocellular carcinoma (HCC) is a frequent and fatal human cancer with poor diagnosis that accounts for over half a million deaths each year worldwide. L. known as oleaster has a wide range of pharmacological activities. This study aimed to investigate the chemopreventive effect of aqueous extract of fruit (AEA) against diethylnitrosamine (DEN)-induced HCC in rats. HCC was induced in rats by a single injection of DEN (200 mg/kg) as an initiator. After two weeks, rats were orally administered 2-acetylaminofluorene or 2-AAF (30 mg/kg) as a promoter for two weeks. Oleaster-treated rats were orally pretreated with the increasing doses of AEA two weeks prior to DEN injection that continued until the end of the experiment. In the current study, a significant decrease in serum biomarkers of liver damage and cancer, including alfa-fetoprotein (AFP), gamma glutamyl transpeptidase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST) was observed in AEA-treated rats when compared to HCC rats. Furthermore, the oleaster extract exhibited antioxidant activity by elevating reduced glutathione (GSH) contents as well as preventing lipid peroxidation in the liver tissues of DEN-treated rats. The relative weight of liver, a prognostic marker of HCC, was also reduced in oleaster-treated rats. To conclude, our results clearly demonstrated that oleaster fruit possesses a significant chemopreventive effect against primary liver cancer induced by DEN in rats. It can be suggested that the preventive activity of oleaster against hepatocarcinogenesis may be mediated through the antioxidant, anti-inflammation, and antimutagenic effects of the fruit.
肝细胞癌（HCC）是一种常见且致命的人类癌症，诊断困难，全球每年有超过50万人死于该病。油橄榄（又称沙枣）具有广泛的药理活性。本研究旨在探讨果实水提取物（AEA）对二乙基亚硝胺（DEN）诱导的大鼠肝癌的化学预防作用。以单次注射DEN（200 mg/kg）作为引发剂诱导大鼠发生HCC。两周后，给大鼠口服2-乙酰氨基芴或2-AAF（30 mg/kg）作为促癌剂，持续两周。在注射DEN前两周，给油橄榄处理组大鼠口服递增剂量的AEA，持续至实验结束。在本研究中，与HCC大鼠相比，观察到AEA处理组大鼠肝脏损伤和癌症的血清生物标志物显著降低，包括甲胎蛋白（AFP）、γ-谷氨酰转肽酶（GGT）、丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）。此外，油橄榄提取物通过提高还原型谷胱甘肽（GSH）含量以及防止DEN处理组大鼠肝组织中的脂质过氧化，表现出抗氧化活性。肝癌的预后标志物肝脏相对重量在油橄榄处理组大鼠中也有所降低。总之，我们的结果清楚地表明，油橄榄果实对DEN诱导的大鼠原发性肝癌具有显著的化学预防作用。可以认为，油橄榄对肝癌发生的预防活性可能是通过果实的抗氧化、抗炎和抗诱变作用介导的。
