Study On The Inhibitory Effects Of Nostoc Sphaeroides On DENA-induced Hepatocarcinogenesis In Mouse

Nostoc sphaeroides has been one kind of edible algae since the ancient time in China. It is rich in polysaccharide and phycobiliprotein, which have a variety of special biological activities, especially its cancer inhibition that receives high attention now in the fields of food and medicine. The aim of the present study was to evaluate the inhibitory effects of Nostoc on the DENA-induced hepatocarcinogenesis in mice. The experiments were divided into four groups, i.e., the control group in which the mice were intraperitoneally injected saline solution and supplied free drink sterile distilled water, the Nostoc group with intraperitoneal injection of saline solution and free drink Nostoc algae slurry instead of sterile distilled water, the DENA group with intraperitoneal injection of DENA and free drink sterile distilled water, and the intervention group with intraperitoneal injection of DENA and free drink Nostoc algae slurry instead of sterile distilled water. The Kunming(KM) mouse(20-22g) was obtained from Experimental Animal Centre of Henan Province, China. All the mice were allowed a free access to a standard rodent pellet diet libitum. After being anesthetized, the mice in each group were sacrificed at 14, 28, 56, 70, and 84 d, respectively, and the serum and liver from control and exposed animals were quickly obtained removed and stored at-80 °C for the following biochemical assays and histopathological examination. The main results obtained in this study are as follows:(1) The mice from the Nostoc group grew faster than those from other groups throughout the whole experiment, and they had a nimble behavior and good mental state and their fur was light. However, the mice from the DENA group ingested less food than those from other groups at the late time of experiment and they were thin and had a bad mental state. In a similar way, the mice from the intervention group also showed the similar symptom to the DENA group, but it occurred later and lighter than that of DENA-treated mice. Moreover, the liver body index of the DENA or intervention group was higher than that in control or Nostoc group. Our results suggest that Nostoc can promote the growth of mouse and have some protective effects on the liver damage in mice induced by DENA.(2) The results of serum biochemical assays showed that the activities of ALT and AST in the DENA or intervention group were significantly higher than that in control or Nostoc group. However, there was no difference in ALT and AST activity between the Nostoc group and the control group. In addition, ALT and AST activity in intervention group was lower than that in DENA group, indicating that supplied Nostoc decreased the liver injury in mice caused by DENA.(3) The results of ELISA showed that the contents of AFP in mouse serum of Nostoc group were at the normal level and no statistical difference was found when compared to the control group. However, an obvious increase of AFP content in the serum of DENA-treated mice was observed in comparasion with that of control mice. For the intervened mice, AFP contents also increased when compared to the control mice, but the increase was slower and slighter than that of DENA group.(4) The results of quantitative real-time PCR showed that the m RNA levels of AFP, bcl-2, and p53 in the liver of the intervented mice were lower than that of DENA-treated mice except for PTEN.(5) The results of histopathological examination showed that inflammatory reaction occurred in the liver of DENA-treated mice from 14 to 28 d and acidophilic degeneration and hyperplasia was observed at 42 to 56 d. After 70 days of DENA-exposure, a great deal of necrosis and carceration of hepatocytes could be found in the liver of DENA-treated mice. However, compared with the DENA-treated mice, necrosis and carceration occurred later in the intervented mice, suggesting that Nostoc may have inhibitory effect on the DENA-induced hepatocarcinogenesis.In conclusion, our results indicate that feeding Nostoc can promote the growth of mouse. Nostoc added to mouse feed not only has intervention effect on the DENA-induced hepatocarcinogenesis, but also has protective step-down effects on the hepatotoxicity and liver damage induced by DENA. Addtionally, feeding Nostoc also delay the progress of hepatocarcinogenesis and prolong the surval time of the DENA-treated mice. This result may be valuable for the research on the development of Nostoc as nutrient food and medicine for human.