AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (...AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA). METHODS: Rats, intravenously (iv ) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip ) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mecha-nisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract. RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. CONCLUSION: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in post-necrotic proliferative liver states.展开更多
The mechanism of a cycloaddition reaction between singlet dichloromethylene germylene and ethylene has been investigated with B3LYP/6-31G* method, including geometry optimization and vibrational analysis for the invo...The mechanism of a cycloaddition reaction between singlet dichloromethylene germylene and ethylene has been investigated with B3LYP/6-31G* method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. Energies for the involved conformations were calculated by CCSD(T)//B3LYP/6-31G* method. On the basis of the surface energy profile obtained with CCSD(T)// B3LYP/6-31G* method for the cycloaddition reaction between singlet dichloromethylene germylene and ethylene, it can be predicted that the dominant reaction pathway is that an intermediate INT1 is firstly formed between the two reactants through a barrier-free exothermic reaction of 61.7 kJ/mol, and the intermediate INT1 then isomerizes to an active four-membered ring product P2.1 via a transition state TS2, an intermediate INT2 and a transition state TS2.1, in which energy barriers are 57.7 and 42.2 kJ/mol, respectively.展开更多
文摘AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA). METHODS: Rats, intravenously (iv ) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip ) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mecha-nisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract. RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. CONCLUSION: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in post-necrotic proliferative liver states.
基金Project supported by the Natural Science Foundation of Shandong Province of China (No. Y2002B07).
文摘The mechanism of a cycloaddition reaction between singlet dichloromethylene germylene and ethylene has been investigated with B3LYP/6-31G* method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. Energies for the involved conformations were calculated by CCSD(T)//B3LYP/6-31G* method. On the basis of the surface energy profile obtained with CCSD(T)// B3LYP/6-31G* method for the cycloaddition reaction between singlet dichloromethylene germylene and ethylene, it can be predicted that the dominant reaction pathway is that an intermediate INT1 is firstly formed between the two reactants through a barrier-free exothermic reaction of 61.7 kJ/mol, and the intermediate INT1 then isomerizes to an active four-membered ring product P2.1 via a transition state TS2, an intermediate INT2 and a transition state TS2.1, in which energy barriers are 57.7 and 42.2 kJ/mol, respectively.