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

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

doi:10.1093/toxres/tfab094

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

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

Affiliations

¹ Biochemistry Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt.
² Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-suef University, Beni-suef, Egypt.
³ Genetics and Genetic Engineering Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.
⁴ Clinical Laboratory Sciences Department, Turabah University College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁵ Department of Pathology, Faculty of Veterinary Medicine, Damanhur University, Damanhur, Egypt.
⁶ Department of Veterinary Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.
⁷ Department of Cytology and Histology, Faculty of Veterinary Medicine, Kafr-Elsheikh University, Kafr-Elsheikh, Egypt.
⁸ Biotechnology Department, College of Science, Taif University, Taif 21995, Saudi Arabia.

Abstract

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/CCl₄ exhibited inhibitory and ameliorative effects against DEN/CCl₄-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/CCl₄-induced HCC in rats.

Keywords: HCC; anti-metastatic; antifibrotic; antioxidant; bee honey.