1.Role of endotoxemia in the development of hepatocarcinoma in rats
Longfeng ZHAO ; Hong LI ; Dew HAN
Chinese Journal of Pathophysiology 2000;0(10):-
AIM: To explore the effect of endotoxemia on hepatocarcinoma course induced by TAA. METHODS: The rat cirrhosis was induced by intaking TAA (0.03%) for four months, hepatocarcinom for six months. Lipoplysaccharide (100 ?g/kg) was administered subcutaneously every two days from the fifth month to the end of sixth month in TAA-treated rats. The plasma endotoxin content, ?-glutamyl transpeptidase(?-GT) activity, DNA index and aneuploidy index were determined, the point mutation of N-ras, p53 gene was detected in hepatocarcinoma rats. RESULTS: Endotoxin increased protein overexpression of p53, bcl-2 and N-ras , p53 gene mutation point and free radical production, reduced antioxidase activity and aggravated DNA damage in hepatocarcinoma rats. CONCLUSION: Endotoxin could accelerate hepatocarcinogenesis promoted by TAA.
2.Role of endotoxemia in the occurrence and development of cirrhosis
Hong LI ; Longfeng ZHAO ; Dew HAN
Chinese Journal of Pathophysiology 1986;0(04):-
AIM: To study the roles of endotoxemia in the occurence and development of cirrhosis. METHODS: The cirrhosis of rats were made by oral intake of thioacetamide (TAA-treated rats). A separate group of rats were subjected to a injection of small dosage of lipopolisaccharride (LPS) in the period of thiocetamide treatment in order to observe the possible effect of LPS on the forming of cirrhosis. RESULTS:Both plasma endotoxin levels and hepatic collagen contents were increased in TAA-treated rats,and there was a linear correlation between them ;Plasma and hepatic tumor necrosis factor (TNF?)、endothelin-1(ET-1)、nitric oxide(NO)、and MDA levels were all increased,and plasma endotoxin was correlated with all of their plasma contents;Only TNF? levels and hepatic collagen contents of TAA+LPS group were increased significantly compared with TAA group. CONCLUSION: These results suggest that endotoxemia (ETM) could play an important role in the development of cirrhosis mainly through activating Kupffer cells, which secrete TNF?, ET-1, NO and free radicals could be involved in the process.