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蜂蜜对二乙基亚硝胺和四氯化碳诱发的Wistar大鼠肝细胞癌的调节作用。

The modulatory effect of bee honey against diethyl nitrosamine and carbon tetrachloride instigated hepatocellular carcinoma in Wistar rats.

作者信息

Abouzed Tarek Kamal, Eldomany Ehab B, Khatab Shymaa A, Aldhahrani Adil, Gouda Wael M, Elgazzar Ahmed M, Soliman Mohamed Mohamed, Kassab Mohmed Atef, El-Shazly Samir Ahmed, Althobaiti Fayez, Dorghamm Doaa Abdallha

机构信息

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

Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-suef University, Beni-suef, Egypt.

出版信息

Toxicol Res (Camb). 2021 Oct 14;10(6):1092-1103. doi: 10.1093/toxres/tfab094. eCollection 2021 Dec.

Abstract

UNLABELLED

Hepatocellular carcinoma (HCC) is a serious threat to human health that has attracted substantial interest. The purpose of this study was to investigate the modulatory effect of bee honey against induced HCC by diethylnitrosamine/carbon tetrachloride (DEN/CCl4) in rats. HCC was induced by a single intraperitoneal dose of DEN (200 mg/kg B.W). Two weeks later, CCl4 (1 ml/kg) was intraperitoneally injected (three times a week). Bee honey was administered orally at 2 g/rat before and after the induction of HCC. The results showed that bee honey administration significantly increased body weight, decreased liver weight, and relative liver weight compared to those in the HCC-induced group. Moreover, a significant decrease in serum alpha-fetoprotein (AFP) as well as AST, ALT, GGT, ALP activities were observed in bee honey administration rats compared with those in HCC-induced group. Also, the hepatic MDA was significantly decreased; in addition, SOD, CAT, and GPx activities were significantly increased in groups treated with bee honey compared with those in the HCC group. The hepatic histopathology alterations caused by DEN/CCl4 injection were ameliorated by bee honey treatment. Likewise, the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor (TGF-β1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), glypican (GP-3), thioredoxin (TRX), and glutaredoxin (GRX) were downregulated, and caspase-3 was upregulated by bee honey treatment compared with untreated HCC-induced group. In conclusion, bee honey has remarkable beneficial effects against HCC induced in rats through its antioxidant, anti-inflammatory, antifibrotic, and antimetastatic effects.

PRACTICAL APPLICATIONS

The current study confirmed that honey has the potential to act as an antimetastatic factor. Bee honey supplementation either before or after combined injection of DEN/CCl exhibited inhibitory and ameliorative effects against DEN/CCl-induced HCC through its antioxidant, antiproliferative, anti-metastatic, antifibrotic, and apoptosis properties. To our knowledge, this is the first study to describe the molecular mechanisms underlying honey's effects against DEN/CCl-induced HCC in rats.

摘要

未标记

肝细胞癌(HCC)对人类健康构成严重威胁,已引起广泛关注。本研究的目的是探讨蜂蜜对二乙基亚硝胺/四氯化碳(DEN/CCl4)诱导的大鼠肝癌的调节作用。通过腹腔注射单次剂量的DEN(200mg/kg体重)诱导肝癌。两周后,腹腔注射CCl4(1ml/kg)(每周三次)。在肝癌诱导前后,以2g/只大鼠的剂量口服蜂蜜。结果表明,与肝癌诱导组相比,给予蜂蜜显著增加了体重,降低了肝脏重量和相对肝脏重量。此外,与肝癌诱导组相比,给予蜂蜜的大鼠血清甲胎蛋白(AFP)以及AST、ALT、GGT、ALP活性显著降低。此外,肝脏MDA显著降低;此外,与肝癌组相比,给予蜂蜜治疗的组中SOD、CAT和GPx活性显著增加。蜂蜜治疗改善了由DEN/CCl4注射引起的肝脏组织病理学改变。同样,与未治疗的肝癌诱导组相比,蜂蜜治疗下调了肿瘤坏死因子-α(TNF-α)、转化生长因子(TGF-β1)、细胞间粘附分子-1(ICAM-1)、血管细胞粘附分子-1(VCAM-1)、磷脂酰肌醇蛋白聚糖(GP-3)、硫氧还蛋白(TRX)和谷氧还蛋白(GRX)的mRNA表达水平,并上调了半胱天冬酶-3。总之,蜂蜜通过其抗氧化、抗炎、抗纤维化和抗转移作用对大鼠诱导的肝癌具有显著的有益作用。

实际应用

本研究证实蜂蜜有潜力作为一种抗转移因子。在联合注射DEN/CCl之前或之后补充蜂蜜,通过其抗氧化、抗增殖、抗转移、抗纤维化和凋亡特性,对DEN/CCl诱导的肝癌表现出抑制和改善作用。据我们所知,这是第一项描述蜂蜜对大鼠DEN/CCl诱导的肝癌作用的分子机制的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d2/8693075/4f24b1bed47d/tfab094ga.jpg

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