1.Model validation and evaluation of developmental toxicity of five drugs using zebrafish embryos
Bingjie XU ; Lijiang ZHANG ; Chunqi LI ; Yaoxian XUAN
Chinese Pharmacological Bulletin 2016;(1):74-78,79
Aim To explore the toxicity and safety of five kinds of known positive drugs, cyclophosphamide, acetyl salicylic acid, tetracycline hydrochloride, dexa-methasone acetate and azacitidine, using zebrafish em-bryos. Methods We selected normally developed 4 hpf zygote, and used water bath infecting method to add the drug to the artificial seawater. Each drug had five concentrating groups, a separate control group and solvent control group. We observed the dead zebrafish embryos after 120 hpf drugs, counted the number of deaths and deformities of zebrafish embryos, and cal-culated mortality abnormal rate, the median lethal con-centration (LC50 ), concentration for 50% of maximal effect (EC50 ), therapeutic index (TI) under 120 hpf condition. We also used the formula TI = LC50 / EC50 to calculate positive drug therapeutic index. Based on measured LC50 we calculated most nonlethal concentra-tion (MNLC) of each drug setting, namely 1 / 10 MN-LC, 1 / 3 MNLC, MNLC,LC10 four concentration, tha-lidomide as a positive control, vitamin C as a negative control, artificial seawater as control, 0. 5% DMSO as solvent control. Put in 28. 5 ℃ environment for 120 hours,embryo development was observed daily for de-velopmental state,mortality,deforming rate and abnor-mal condition. Results The result of five drugs LC50 in descending order: cyclophosphamide > azacitidine> tetracycline hydrochloride > acetylsalicylic acid >dexamethasone acetate. EC50 in descending order: cy-clophosphamide > tetracycline hydrochloride > azaciti-dine > acetylsalicylic acid > dexamethasone acetate. The TI values of cyclophosphamide, acetyl salicylic acid, tetracycline hydrochloride, dexamethasone ace-tate, azacitidine were 1. 92, 1. 11, 1. 05, 1. 44, 2. 99, respectively. Conclusion Zebrafish embryo model can be used in the preliminary evaluation of drugs, and the study of early developmental toxicity and safety.
3.Study on the application of zebrafish model in the early stage of renal toxicity in drug development
Jinfeng LIANG ; Yong ZHU ; Hongyao ZHANG ; Qiaocong LAO ; Minkang MA ; Chunqi LI
Chinese Journal of Comparative Medicine 2016;26(9):30-35
Objective To evaluate the renal toxicity of vancomycin hydrochloride and irbesartan tablets using the zebrafish model. Methods After construction of AB zebrafish kidney model, the fish were treated with drug after fertilization 2 days (2 dpf) to 5 dpf. At the end of the experiment, the number of renal edema zebrafish was counted in each experimental group to evaluate the renal toxicity of drugs. Results The zebrafish development was normal and no obvious toxicity at the dose of 16?4 ng/fish (1/10 MNLD) for vancomycin, and zebrafish renal edema occurred rate was 3?3%, 10% and 10% respectively at the dose of 54?7 ng/fish (1/3 MNLD), 164 ng/fish (MNLD) and 273 ng/fish ( LD10 ) with the death rate of 0%, 0% and 16?7%, respectively, which indicated that there was significant renal toxicity of vancomycin at the dose of 54?7 ng/fish (1/3MNLD) to 273 ng/fish (LD10). Irbesartan didn’t induce renal toxicity at the dose of 8?3 μg/mL (1/10 MNLC) to 91 μg/mL (LC10). Conclusions The zebrafish model of renal toxicity can be used for the early evaluation of drug renal toxicity and we made evaluation of the renal toxicity of vancomycin and irbesartan with this model.
4.A new loading bioreactor for bone tissue-engineering applications.
Chunqi ZHANG ; Xizheng ZHANG ; Furong WANG ; Jinhui WU ; Yuexin WANG ; Qingfei LU
Journal of Biomedical Engineering 2005;22(4):804-832
Bone cells live in an environment heavily influenced by mechanical force. The development of bone tissue is dependent on the environment that surrounds it, both in vivo and in vitro. A loading stimulator on research of bone tissue-engineering was developed based on the mechanism of mechanosensation, scaffolding composites with mechanical strains with more physiologic magnitude, frequency components, and waveform. It also achieves the mechanical environment particularly in hard scaffold enough strong like cancellous bone. The device was tested using a reference scaffold made of better elastic plastic material. The experiment results showed that the device could be used in precision strain controls. Since the drive of the stimulator comes from the usage of smart material, piezoceramics, the strain at physiological level is controlled precisely. The stimulator provides a mechanical condition under which the effects of loading applied on bone tissue-engineering culture are conveniently investigated. Furthermore, after the stimulator is improved, it will be an appropriate bioreactor for bone tissue-engineering culture.
Bioreactors
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Bone and Bones
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cytology
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Cell Differentiation
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Cells, Cultured
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Humans
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Mechanotransduction, Cellular
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Osteoblasts
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cytology
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metabolism
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Stress, Mechanical
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Tissue Engineering
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instrumentation
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methods
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Tissue Scaffolds