In the present study, cultured human SHG-44 glioma cells were subjected to a hypoxic environment simulated using the CoOl2 method. Flow cytometry showed increased reactive oxygen species production in these cells. Rea...In the present study, cultured human SHG-44 glioma cells were subjected to a hypoxic environment simulated using the CoOl2 method. Flow cytometry showed increased reactive oxygen species production in these cells. Real-time reverse transcription-PCR showed significantly increased hypoxia-inducible factor-la mRNA expression in cells exposed to the hypoxic condition. The antioxidant N-acetylcysteine significantly inhibited reactive oxygen species production and reduced hypoxia-inducible factor-la mRNA expression in normoxic and hypoxic groups, especially in the latter group. These findings indicate that hypoxia induces reactive oxygen species production and hypoxia-inducible factor-la mRNA expression in human SHG-44 glioma cells, and that the antioxidant N-acetylcysteine can inhibit these changes.展开更多
The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokin...The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific^(131)I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of^(131)I-Kringle 5 in vivo, and to investigate the dynamic distributions of^(131)I-Kringle 5 in target organs. Labeling recombinant angiogenesis inhibitor Kringle 5 using131 I with longer half-life and imaging in vivo using SPECT instead of PET,could overcome the limitations of previous methods. When the doses of^(131)I-Kringle 5 were 10.0, 7.5 and5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0 1)among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio(2:1.5:1.0). It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after^(131)I-Kringle 5 was injected,^(131)I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that^(131)I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of^(131)I-Kringle 5, the radionuclide in the heart, kidneys,liver and other organs was gradually reduced, while more radionuclide was concentrated in the bladder.The radionuclide was completely metabolized within 24 h, and the distribution of radioactivity in rats was similar to normal levels. In our study, the specific marker^(131)I-Kringle 5 and SPECT/CT were successfully used to explore pharmacokinetic characteristics of Kringle 5 in rats. The study could provide a new evaluation platform of the specific, in vivo and real-time functional imaging and pharmacokinetics for the clinical application of^(131)I-Kringle 5.展开更多
文摘In the present study, cultured human SHG-44 glioma cells were subjected to a hypoxic environment simulated using the CoOl2 method. Flow cytometry showed increased reactive oxygen species production in these cells. Real-time reverse transcription-PCR showed significantly increased hypoxia-inducible factor-la mRNA expression in cells exposed to the hypoxic condition. The antioxidant N-acetylcysteine significantly inhibited reactive oxygen species production and reduced hypoxia-inducible factor-la mRNA expression in normoxic and hypoxic groups, especially in the latter group. These findings indicate that hypoxia induces reactive oxygen species production and hypoxia-inducible factor-la mRNA expression in human SHG-44 glioma cells, and that the antioxidant N-acetylcysteine can inhibit these changes.
文摘The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific^(131)I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of^(131)I-Kringle 5 in vivo, and to investigate the dynamic distributions of^(131)I-Kringle 5 in target organs. Labeling recombinant angiogenesis inhibitor Kringle 5 using131 I with longer half-life and imaging in vivo using SPECT instead of PET,could overcome the limitations of previous methods. When the doses of^(131)I-Kringle 5 were 10.0, 7.5 and5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0 1)among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio(2:1.5:1.0). It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after^(131)I-Kringle 5 was injected,^(131)I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that^(131)I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of^(131)I-Kringle 5, the radionuclide in the heart, kidneys,liver and other organs was gradually reduced, while more radionuclide was concentrated in the bladder.The radionuclide was completely metabolized within 24 h, and the distribution of radioactivity in rats was similar to normal levels. In our study, the specific marker^(131)I-Kringle 5 and SPECT/CT were successfully used to explore pharmacokinetic characteristics of Kringle 5 in rats. The study could provide a new evaluation platform of the specific, in vivo and real-time functional imaging and pharmacokinetics for the clinical application of^(131)I-Kringle 5.
