Selenium(Se),a potential drug candidate for cancer prevention,has a special property:Its nutritional dosage and tolerable upper intake level appear in a narrow range,while the therapeutic use of this mineral may depend on a higher body intake level.Nano-selenium(nano-Se) particles,however,preserve the selenium element's low toxicity characteristic but give a high biochemical activity effect of selenium compounds.In the present study different morphologies of synthesized nano-Se were evaluated concerning its anti-proliferation and apoptosis-inducing effect.Then nano-Se(sphere) were picked out to investigate its influence on two significant events involved in apoptosis,cell cycle arrest and mitochondrial membrane potential disruption.Furthermore,massive vacuolization of HeLa cells treated by nano-Se(sphere) was observed and more methods were used to measure the level of vacuolization.Such vacuolization needs energy supply and has been demonstrated to be related to Se endocytosis.These results suggest a possible mechanism to trigger apoptosis initiation.
BACKGROUND: Worldwide, about 25% of individuals with chronic hepatitis B have fatty liver disease. Lipogenic diets that are completely devoid of methionine and choline induce nonalcoholic fatty liver disease. However, no animal model of nonalcoholic steatohepatitis associated with HBV infection is available, and the influence of viral infection on nutritional hepatic steatosis is unclear. METHODS: We used HBV surface antigen transgenic mice (HBs-Tg mice), which mimic healthy human carriers with hepatitis B surface antigen. The mice were fed with a high-fat methionine-choline-deficient diet (MCD) to build a reliable rodent nutritional model of nonalcoholic steatohepatitis associated with HBV infection, and the changes in body weight and serum triglycerides were measured. Hepatocyte ballooning changes were determined by hematoxylin and eosin staining. The extent of hepatic fat accumulation was evaluated by oil red O staining. Immunohistochemical assays were performed to detect proliferating cell nuclear antigen as an index of cell proliferation. RESULTS: MCD feeding provoked systemic weight loss and liver injury. MCD feeding caused more macrovesicular fat droplets and fat accumulation in the livers of HBs-Tg mice than in wild-type C57BL/6 mice. In addition, within 30 days of MCD exposure, more PCNA-positive nuclei were found in the livers of HBs-Tg mice. CONCLUSIONS: HBs-Tg mice fed with a lipogenic MCD form more macrovesicular fat droplets earlier, coincident with more hepatocyte proliferation, resulting in the appearance of increased susceptibility to experimental steatohepatitis in these mice.
