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高良姜根茎提取物对顺铂治疗肝癌大鼠的化疗增敏作用。

Chemosensitizing effect of Alpinia officinarum rhizome extract in cisplatin-treated rats with hepatocellular carcinoma.

机构信息

Biochemistry Department, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt.

Biochemistry Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt.

出版信息

Biomed Pharmacother. 2018 May;101:710-718. doi: 10.1016/j.biopha.2018.02.128. Epub 2018 Mar 22.

Abstract

This study was conducted to estimate the preventing and sensitizing efficiency of Alpinia officinarum rhizome extract (AORE) in an experimental model of hepatocellular carcinoma (HCC) +/- cisplatin. HCC was induced by a single intraperitoneal (i.p) dose of diethylnitrosamine (DENA, 200mg/kg). After 14 days, phenobarbitone (PB, 0.05%) was added to drinking water for 14 weeks to promote hepatocarcinogenesis. Cisplatin (CP) was given in a dose of 1.5 mg/kg (i.p), twice a week, alone or with AORE (400 mg/kg daily, orally) for 21 days. AORE was tried as a protective before the induction of HCC for three weeks as well. Results revealed that DENA/PB elevated hepatic indices as ALT and AST and total bilirubin with declining serum total protein. It increased oxidative stress, as hepatic malondialdehyde (MDA) with depressed hepatic reduced glutathione (GSH) contents, superoxide dismutase (SOD) and catalase activities. This was accompanied by an increase in hepatic expression of antioxidant genes (thioredoxin and glutaredoxin). Hepatocarcinogenesis was detected by histopathological changes in liver sections and the elevation of serum alpha-fetoprotein (AFP) level. Treatment with CP partially restored altered hepatic functions and oxidative stress markers. It also showed a partial decrease in the expression of antioxidant genes, improving histopathological changes in the liver and AFP level in serum. The treatment with AORE alone or AORE+CP enhanced hepatic function and oxidative stress markers. It also caused a decrease in the expression of antioxidant genes and improved histopathological changes in liver and serum AFP level. This effect is more potent than the treatment with CP alone. Our study suggested that AORE can be used as a promising natural chemoprevention or a chemosensitizing agent against hepatocarcinogenesis.

摘要

这项研究旨在评估高良姜根茎提取物(AORE)在实验性肝癌(HCC)/±顺铂模型中的预防和致敏效率。HCC 是通过单次腹腔内(i.p)给予二乙基亚硝胺(DENA,200mg/kg)诱导的。14 天后,将苯巴比妥(PB,0.05%)添加到饮用水中 14 周以促进肝癌发生。顺铂(CP)以 1.5mg/kg(i.p)的剂量单独或与 AORE(400mg/kg,每日口服)一起使用,每周两次,共 21 天。AORE 也尝试在 HCC 诱导前作为保护剂使用了三周。结果表明,DENA/PB 升高了肝指数,如 ALT 和 AST 以及总胆红素,同时血清总蛋白降低。它增加了氧化应激,如肝丙二醛(MDA)与肝还原型谷胱甘肽(GSH)含量、超氧化物歧化酶(SOD)和过氧化氢酶活性降低。这伴随着抗氧化基因(硫氧还蛋白和谷氧还蛋白)在肝脏中的表达增加。肝癌发生通过肝组织切片的组织病理学变化和血清α-胎蛋白(AFP)水平的升高来检测。CP 治疗部分恢复了改变的肝功能和氧化应激标志物。它还显示抗氧化基因的表达部分减少,改善了肝脏的组织病理学变化和血清 AFP 水平。单独使用 AORE 或 AORE+CP 治疗可增强肝功能和氧化应激标志物。它还导致抗氧化基因的表达减少,并改善了肝脏的组织病理学变化和血清 AFP 水平。这种效果比单独使用 CP 治疗更有效。我们的研究表明,AORE 可用作有前途的天然化学预防剂或化学增敏剂,用于预防肝癌发生。

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