3.The effect of ligustrazine on peritoneal transport in peritoneal dialysis.
Zhonghua, ZHU ; Weiyi, PENG ; Yumei, WANG ; Hongyan, ZHU ; Xiao, YANG ; Anguo, DENG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(4):334-6
In order to investigate the effect of ligustrazine (Lig) i.p. on peritoneal permeability in peritoneal dialysis and its side effects, creatinine was given intravenously and continuously to maintain the high plasma creatinine level. All the rabbits were divided into three groups: normal control group (group A), group B treated with 0.12% Lig and group C treated with 0.24% Lig. The peritoneal dialysis of all rabbits lasted 2 h. The plasma and dialysate levels of glucose, protein and creatinine were observed immediate, 30 min, 60 min, 90 min, 120 min after dialysis. Creastinine dialysate/plasma ratio (D/P), protein D/P ratio, glucose D/Do at different time points after dialysis and creatinine mass transfer area coefficient (MTAC) at 120 min were calculated. The structures of peritoneum were observed under optical microscope and electron microscope after continuously intraperitoneal injection of Lig for 14 days. The results showed that the 90-min and 120-min creatinine D/P ratios in the group C were higher than in the group A. The 120-min creatinine MATC in the group C was higher than in the group A. The rabbits treated with Lig did not show significant structure changes of peritoneum and signs of peritoneal irritation. It was suggested that Lig could increase mass transfer ability of peritoneum without significant side effects.
Biological Transport
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Cell Membrane Permeability
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Creatinine/blood
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Dialysis Solutions/chemistry
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Peritoneal Dialysis/*methods
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Peritoneum/*metabolism
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Pyrazines/*pharmacokinetics
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Pyrazines/pharmacology
4.Effect of bortezomib and arabinoside on proliferation and apoptosis of K562 cell..
Chinese Journal of Hematology 2010;31(1):42-45
OBJECTIVETo investigate the effect of bortezomib (Bor) alone and in combination with arabinoside (Ara-C) on proliferation and apoptosis of leukemia cell line K562.
METHODSK562 cells were treated with 20 nmol/L Bor and 0.2 microg/ml Ara-C alone and in combination for 48 h. MTT was used to study the inhibitory effects on cell growth and the apoptosis rate was analysed by flow cytometry. After K562 cells treated with 20 nmol/L Bor or 0.2 microg/ml Ara-C for 6 h, the activity of NF-kappaB was analyzed by SP immunohistochemistry and cell cycle by flow cytometry.
RESULTSThe inhibition and apoptosis rates of K562 cells in combination groups were higher than those in the two single treatment groups (P < 0.01), especially in the combined treatment group in which K562 cells were treated first with Ara-C for 6 h then with Bor combined,the inhibition and apoptosis rates were the highest [(81.5 +/- 4.0)% and (29.2 +/- 3.1)%, respectively] (P < 0.01). In the other two combined groups in which the cells were treated with Bor for 6 h then with Ara-C combined, or treated with the two drugs simultaneously, the inhibition and apoptosis rates were (54.1 +/- 4.2)% and (18.7 +/- 3.5)%, and (66.2 +/- 2.8)% and (21.1 +/- 2.2)%, respectively. Treatment of K562 cells with 20 nmol/L Bor for 6 h, the activity of NF-kappaB was decreased significantly, and the cells were apparently arrested in G(2)/M phase, and treatment with 0.2 microg/ml Ara-C in the same manner, the activity of NF-kappaB was increased significantly, and the cells were apparently arrested in G(1) phase.
CONCLUSIONSBor can effectively inhibit K562 cell proliferation, and induced its apoptosis. This effect was enhanced significantly when in combination with Ara-C. Pretreatment of K562 cells with Ara-C lead to the increased activity of NF-kappaB and the fraction of G(1) phase cells.
Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Proliferation ; drug effects ; Humans ; K562 Cells ; Pyrazines ; pharmacology
5.2-methoxyestradiol disrupts aggresomes induction by bortezomib and potentiates apoptosis in multiple myeloma cells..
Yang-Li MA ; Hua JIANG ; Jian HOU
Chinese Journal of Hematology 2009;30(11):754-757
OBJECTIVETo investigate the synergistic anti-multiple myeloma (MM) effect of 2-methoxyestradiol (2-ME2) and bortezomib, and explore the relationship between this effect and blockade of aggresomes formation by 2-ME2.
METHODSFour MM cell lines RPMI-8226, NCI-H929, U266 and SKO-007 were used for study. Immunoflourescent anti-ubiquitin and Hoechst 33342 staining were used to examine aggresome-positive cells and apoptotic cells, respectively. Isobolographic analysis was used for determination of synergy.
RESULTS(1) Quantitative assay showed that in the absence of bortezomib, only 6.6% - 8.9% of MM cells were aggresome-positive, but the percentage was increased to 71.9%-83.4% after treatment with bortezomib at IC(20) concentration for 24 h. Aggresome-positive cells with immunoreactivity to anti-ubiquitin were detected in almost all non-apoptotic cells, but not in apoptotic cells. (2) Treatment in a definite range of concentrations bortezomib plus 2-ME2 led to MM cell apoptosis compared with each agent alone and the significantly synergistic effect confirmed by isobolographic analysis. (3) Combination of bortezomib and 2-ME2 increased the apoptotic cells aggresome-negative cells (ANK) and decreased the non-apoptotic cells in aggresome positive cells (APC). In RPMI8226 and U266 cells, the apoptotic cells in ANC increased from (14.5 +/- 2.0)% and (20.1 +/- 2.9)% to (80.7 +/- 6.9)% and (71.6 +/- 6.2)%, and the non-apoptotic cells in APC decreased from (75.3 +/- 5.7)% and (69.1 +/- 8.6)% to (13.8 +/- 3.8)% and (19.5 +/- 4.2)%, respectively, in combined group and bortezomib alone group.
CONCLUSIONBortezomib-induced aggresomes have a protective function for MM cells and combination of bortezomib with 2-ME2 induced a synergistic cytotoxicity to the cells.
Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Humans ; Multiple Myeloma ; metabolism ; Pyrazines ; pharmacology
6.Effect of bortezomib and low concentration cytarabine on apoptosis in U937 cell line.
Xin DU ; Pei-Min JIA ; Cong HE ; Sheng-Hong DU ; Jian-Hua TONG ; Li ZHOU
Journal of Experimental Hematology 2012;20(3):554-557
This study was aimed to explore the effect of bortezomib and low concentration cytarabine (Ara-C) on proliferation and apoptosis in U937 cell line and its mechanism. The proliferation and apoptosis of U937 cells treated with bortezomib (10 nmol/L) and(or) Ara-C (50 nmol/L) were observed by cell count, cell morphology, flow cytometry and Western blot. The results showed that bortezomib and Ara-C alone inhibited U937 cell proliferation. The inhibitory effect was enhanced by combination of these two drugs, the inhibitory rates of U937 cell proliferation were (55.00 ± 2.81)% and (70.02 ± 3.33)% after treatment for 24 h and 48 h, respectively. Bortezomib and Ara-C synergistically induced apoptosis and decreased mitochondrial membrane potential in U937 cells. The percentage of Rhodamin123 positive cells was (38.70 ± 1.54)%. Bortezomib and Ara-C also synergistically induced activation of caspase-9, caspase-8 and caspase-3. It is concluded that the bortezomib and low concentration Ara-C synergistically induced apoptosis in U937 cells, mainly through mitochondrial pathway, and possibly through death receptor pathway.
Apoptosis
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drug effects
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Boronic Acids
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pharmacology
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Bortezomib
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Cell Cycle
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drug effects
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Cytarabine
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pharmacology
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Humans
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Pyrazines
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pharmacology
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U937 Cells
8.Effect of puerarin and ligustrazine on cultured hippocampal neurons injury induced by Abeta25-35.
Yu WANG ; Hai-Tong WAN ; Wei-Min YAN ; Jie-Hong YANG ; Ying GUO ; Yuan-Jiang PAN ; Jin HAN ; Qin YU
China Journal of Chinese Materia Medica 2008;33(4):424-427
OBJECTIVETo investigate the changes of MDA, SOD, LDH of cultured hippocampal neurons injury induced by amyloid-beta protein (Abeta 25-35) and the protective effect of puerarin and ligustrazine.
METHODPrimary hippocampal neurons were cultured and induced by Abeta 25-35. The concentrations of MDA, SOD and LDH in cultured hippocampal neurons were measured after exposed to Abeta 25-35, puerarin and ligustrazine.
RESULTThe Alzheimer disease (AD) model was successfully established in cultured hippocampal neurons. AD group has remarkably increased MDA and LDH level, and decreased SOD level, Piracetan group and combined application group of have remarkably decreased MDA and LDH level and increased SOD level, compared with AD group (P < 0.01). Ligustrazine together with puerarin group has remarkably decreased MDA and LDH level and increased SOD level, compared with ligustrazine group and puerarin group (P < 0.05).
CONCLUSIONAbeta 25-35 can induce cultured hippocampal neurons injury, combined application of ligustrazine, and puerarin can alleviate the injury.
Amyloid beta-Peptides ; pharmacology ; Animals ; Cells, Cultured ; Hippocampus ; cytology ; Isoflavones ; pharmacology ; Neurons ; drug effects ; Pyrazines ; pharmacology ; Rats
10.Synergistic effects of arsenic trioxide and proteasome inhibitor bortezomib on apoptosis induction in Raji cell line.
Yi HE ; Jian-Min YANG ; Jian-Min WANG ; Hong ZHOU ; Shu-Qing LÜ ; Xiao-Xia HU
Journal of Experimental Hematology 2008;16(4):794-798
The aim of this study was to explore the synergistic effect of arsenic trioxide and bortezomib on apoptosis of Raji cell line. The cells were treated with arsenic trioxide, bortezomib, low-dose arsenic trioxide combined with bortezomib, respectively. The cell viability and proliferative curve were estimated by trypan blue dye exclusion. The cell apoptosis and cell cycle status were analyzed by flow cytometry. The apoptosis related elements such as caspase-3, BCL-2, BAX, JNK2 and IkappaB-alpha, were measured with Western blot. The results showed that compared with cells treated with mentioned above drugs alone, the proliferative potential of cells in combination group was significantly inhibited (p < 0.01), and apoptosis rate markedly increased (p = 0.001), while obvious cell cycle arrest was not observed. On the protein level, the expression of Caspase-3, BAX and IkappaB-alpha increased, while the expression of BCL-2, and JNK2 decreased. It is concluded that low-dose arsenic trioxide combined with bortezomib synergistically induced apoptosis in Raji cell line which may be mediated by inhibiting NK-kappaB and JNK2 signaling.
Antineoplastic Agents
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pharmacology
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Apoptosis
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drug effects
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Arsenicals
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pharmacology
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Boronic Acids
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pharmacology
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Bortezomib
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Burkitt Lymphoma
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pathology
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Cell Line, Tumor
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Drug Synergism
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Humans
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Oxides
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pharmacology
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Protease Inhibitors
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pharmacology
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Pyrazines
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pharmacology