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Sulforaphane inhibits diethylnitrosamine-induced hepatocellular carcinoma tumorigenesis in rats
Authors:FENG Ming-hui  HE Song-qi  DONG Xiao-fei  ZHAO Xiao-qing  LIN Zheng  WANG Jia-ji  PANG Jie
Institution:1. Department of Oncology, Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510000, China; 2. School of Chinese Medicine, Southern Medical University, Guangzhou 510515, China
Abstract:AIM: To investigate the inhibitory effect of sulforaphane (SFN) on the hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) and its possible mechanism. METHODS: DEN was repeatedly injected into the SD rats to induce HCC model, and different doses (0.19 mg/kg, 0.38 mg/kg and 0.57 mg/kg) of SFN were given at the initial symptoms of fibrosis or cirrhosis. The morphological changes of liver specimens and the number of cancerous nodules were observed, and the degree of hepatocyte injury and hepatocellular carcinogenesis were evaluated by HE and Masson staining. The levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin (TBIL), alanine aminotransferase (ALT), interleukin (IL)-1α, IL-6, IL-10, IL-1β, tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in liver tissues were measured by ELISA. The activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and content of mdlondialdehyde (MDA) in liver tissues were detected by spectrophotometry method. RESULTS: Macroscopic observation showed that the number of cancerous nodules in SFN intervention groups was lower than that in DEN group, and the dosage of SFN was negatively correlated with the degree of liver canceration. HE staining and Masson staining showed that SFN inhibited the liver canceration and inflammatory cell infiltration induced by DEN, and the degree of alleviation was positively correlated with the dosage of SFN. The data of ELISA showed that SFN attenuated the hepatocyte injury induced by DEN, and the higher the concentration of SFN was used, the lower the levels of AST, ALT, TBIL and ALP in liver tissues were detected. The levels of inflammatory factors IL-1α, IL-6, IL-1β and TNF-α in liver tissues were decreased after administration of SFN, and the degree of reduction was positively correlated with the concentration of administration, while the levels of inflammatory factors IL-10 and TGF-β were positively correlated with the concentrations of SFN. The activity of SOD, CAT and GPx was decreased with the increase in SFN concentration. CONCLUSION: SFN has a certain inhibitory effect on the liver cancer development induced by DEN, which may be related to the anti-inflammatory, antioxidant and liver injury-reducing effects of SFN.
Keywords:Sulforaphane  Inflammation  Oxidative stress  Hepatocellular carcinoma  Diethylnitrosamine  
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