The Investigation On Anti-tumor And Hepatoprotective Effects Of 5-HMF And Maltol

Accumulating evidences indicated that long-term alcohol abuse and alcohol dependence lead to many diseases,such as malnutrition and alcoholic liver diseases(ALD).Generally,oxidative stress and lipid peroxidation are known to play an important role in the pathogenesis of ALD Since oxidative stress is involved the development of ALD,using the antioxidants would potentially blunt ethanol-induced oxidative stress and prevent pathogenesis.Therefore,the predominant source of antioxidants and their role in prevented ethanol-induced liver injury is an important target.Hepatocellular carcinoma(HCC)is the fifth most prevalent tumor type and the third leading cause of cancer-related mortality worldwide.Although surgical managements can cure the early stage HCC,advanced stage HCC is easy to relapse and becomes fatal.Chemotherapy is one of the important methods for the treatment of tumor,but many lines of evidences showed that the antitumor activities of many chemotherapeutic agents resulted in severe side effects.Recently,natural medicines with better effectiveness and lower toxicity have received more and more attentions as a potential origin of new therapeutic anti-tumor drugs for HCC patients.The aim of this paper is to evaluate the protective effect of 5-hydroxymethyl-2-furfural(5-HMF)on acute alcohol-induced liver oxidative injury in mice.5-HMF,a maillard reaction product,was isolated from the fruits of Schisandra chinensis for animal experiment.Experimental ICR mice were pretreated with different doses of 5-HMF(7.5,15,and 30 mg/kg)for 7 days by gavage feeding.Biochemical markers and enzymatic antioxidants from serum and liver tissue were examined.Our results showed that the activities of ALT(alanine aminotransferase),AST(aspartate transaminase),TC(total cholesterol),TG(triglyceride),L-DLC(low density lipoprotein)in serum and the levels of MDA(malondialdehyde)in liver tissue,decreased significantly(P<0.05)in the 5-HMF-treated group compared with the alcohol group.On the contrary,enzymatic antioxidants CAT(catalase),GSH-Px(glutathione peroxidase),GSH SOD(superoxide dismutase)in liver tissue were elevated markedly treated with 5-HMF(P<0.05).Furthermore,the hepatic levels of pro-inflammatory response marker tumor necrosis factor-alpha(TNF-?)and Interleukin-1?(IL-?)was significantly suppressed(P<0.05).Histopathological examination revealed that 5-HMF(30 mg/kg)pretreatment noticeably prevented alcohol-induced hepatocyte apoptosis and fatty degeneration.It was suggested that the hepatoprotective effects exhibited by 5-HMF on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.The purpose of this study is to investigate the anti-hepatoma activity of maltol,a Maillard reaction product,in H22 tumor-bearing mice.The results demonstrate that maltol not only significantly inhibited the growth of hepatoma H22 transplanted in mice,but also prolonged the survival time of H22-bearing mice.Furthermore,the levels of serum cytokines in H22 tumor-bearing mice,such as interferon gamma(IFN-?),tumor necrosis factor-?(TNF-?),interleukin-6(IL-6),and interleukin-2(IL-2),were enhanced by maltol treatment.Importantly,immunohistochemical and western blotting analysis clearly show that maltol treatment increased Bax and decreased Bcl-2 protein expression levels of H22 tumor tissues in a dose-dependent manner.Collectively,our findings in the present study clearly demonstrate that the maltol markedly suppressed the tumor growth of H22 transplanted tumor in vivo at least partly via improving the immune functions,inducing apoptosis,and inhibiting angiogenesis.