Abstract
Background:This study was conducted to assess the therapeutic effect of Myrrh on Diethylnitrosamine (DEN)-induced hepatocarcinogenesis (HCC) in male albino rats. Methods:Fifty male albino rats were divided into five groups (10 rats each). Group 1 (control group) received distilled water. Group 2 (positive control) was injected intraperitoneally with DEN (55 mg/kg b.w) twice a week for two weeks, while group 3 (DOX) received doxorubicin i.p (10 mg/ kg b.w) after concomitant with DEN twice a week for four weeks. Groups 4 and 5 received a low dose of Myrrh (250 mg/kg b.w) and a high dose of Myrrh (500 mg/kg b.w) respectively daily for four weeks after the induction with DEN. The sera were used to estimate the liver enzymes (ALT, AST, and ALP), Alpha-fetoprotein (AFP), Total antioxidant capacity (TAC), and Tumor necrosis factor-ἁ (TNF-ἁ). Also, the liver tissues were collected to determine the oxidative stress markers in addition to the histopathological and immunohistochemical investigations. Results:The results showed that the induction of DEN causes a significant increase in the level of liver enzymes (ALT, AST, and ALP), AFP and TNF-ἁ as well as produce oxidative stress indicated by increasing of malondialdehyde (MDA) with the reduction in TAC and glutathione (GSH). Meanwhile, there are noticeable histopathological lesions with loss of hepatic architecture. This was accompanied by a significant increase of immunohistochemical markers; Caspase-3, vascular endothelial growth factor (VEGF), transforming growth factor β1(TGF- β1), and carcinoembryonic antigen (CEA) percentage area. The treatment of DEN rats with DOX reduced the alterations in most parameters. A marked amelioration of all parameters in a dose-dependent manner of Myrrh to the values almost near to those of the control group. Conclusion:Our data revealed that Water extract of Myrrh (C. molmol) has a potential therapeutic effect in attenuation of HCC induced DEN.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common tumor and the fourth leading cause of cancer-associated death worldwide (Bray et al, 2018) and accounts for 80 – 90 % of all main liver cancers (Vogel et al, 2018)
The results showed that the induction of DEN causes a significant increase in the level of liver enzymes (ALT, AST, and alkaline phosphatase (ALP)), AFP and Tumor necrosis factor-ἁ (TNF-ἁ) as well as produce oxidative stress indicated by increasing of malondialdehyde (MDA) with the reduction in Total antioxidant capacity (TAC) and glutathione (GSH)
The administration of DEN to rats produced an acute hepatic injury manifested by a significant increase (p
Summary
Hepatocellular carcinoma (HCC) is the sixth most common tumor and the fourth leading cause of cancer-associated death worldwide (Bray et al, 2018) and accounts for 80 – 90 % of all main liver cancers (Vogel et al, 2018). Many factors cause cirrhosis that increases the risk of HCC (Fong et al, 2010) as viral infection with the hepatitis B or hepatitis C (Arzumanyan et al, 2013), alcoholism (Scoccianti et al, 2016), congenital metabolic diseases, diabetes, and smoking (Chuang et al, 2009) along with exposure to carcinogenic compounds as aflatoxins (Cai et al, 2020). Results: The results showed that the induction of DEN causes a significant increase in the level of liver enzymes (ALT, AST, and ALP), AFP and TNF-ἁ as well as produce oxidative stress indicated by increasing of malondialdehyde (MDA) with the reduction in TAC and glutathione (GSH). Conclusion: Our data revealed that Water extract of Myrrh (C. molmol) has a potential therapeutic effect in attenuation of HCC induced DEN
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