Pub Date : 2020-01-01DOI: 10.3867/j.issn.1000-3002.2020.12.001
L. Han, T. X. Wang, Z. Xiao, Wen-xia Zhou, Yongxiang Zhang
The outbreak of coronavirus disease-19 (COVID-19) caused by novel coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) has posed a serious threat to public health. Virus particles of SARS-CoV-2 are composed of outer envelopes and inner nucleocapsids. The nonstructural and structural proteins encoded by the genome play an important role in the whole life cycle of their adsorption, penetration, uncoating, synthesis of nucleic acids and proteins, assembly and liberation. Antiviral drugs can be developed to target the virus itself or key host molecules for virus infection. So far, antibody drugs targeting spike glycoprotein S and small molecule drugs targeting RNA polymerase have shown antiviral effects. They are currently more promising candidate drugs. However, their efficacy still needs to be proved by further clinical trials, and miracle antiviral drugs have not yet appeared. Considering the virus and host targets, the combination therapy of multi-targets and multidrugs, may achieve better therapeutic effect. In this paper, the structure and life cycle of SARS-CoV-2, the research progress in potential targets and drugs were reviewed to provide useful information for the development of anti-SARS-CoV-2 drugs.
{"title":"Research progress in targets and drugs for novel coronavirus","authors":"L. Han, T. X. Wang, Z. Xiao, Wen-xia Zhou, Yongxiang Zhang","doi":"10.3867/j.issn.1000-3002.2020.12.001","DOIUrl":"https://doi.org/10.3867/j.issn.1000-3002.2020.12.001","url":null,"abstract":"The outbreak of coronavirus disease-19 (COVID-19) caused by novel coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) has posed a serious threat to public health. Virus particles of SARS-CoV-2 are composed of outer envelopes and inner nucleocapsids. The nonstructural and structural proteins encoded by the genome play an important role in the whole life cycle of their adsorption, penetration, uncoating, synthesis of nucleic acids and proteins, assembly and liberation. Antiviral drugs can be developed to target the virus itself or key host molecules for virus infection. So far, antibody drugs targeting spike glycoprotein S and small molecule drugs targeting RNA polymerase have shown antiviral effects. They are currently more promising candidate drugs. However, their efficacy still needs to be proved by further clinical trials, and miracle antiviral drugs have not yet appeared. Considering the virus and host targets, the combination therapy of multi-targets and multidrugs, may achieve better therapeutic effect. In this paper, the structure and life cycle of SARS-CoV-2, the research progress in potential targets and drugs were reviewed to provide useful information for the development of anti-SARS-CoV-2 drugs.","PeriodicalId":10149,"journal":{"name":"Chinese Journal of Pharmacology and Toxicology","volume":"34 1","pages":"881-898"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70223333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-11-01DOI: 10.3867/J.ISSN.1000-3002.2017.11.011
Chunyan Pei, Shu Wang, Chun-li Zhang
{"title":"Cell transdifferentiation for neurological disorders: Research progress","authors":"Chunyan Pei, Shu Wang, Chun-li Zhang","doi":"10.3867/J.ISSN.1000-3002.2017.11.011","DOIUrl":"https://doi.org/10.3867/J.ISSN.1000-3002.2017.11.011","url":null,"abstract":"","PeriodicalId":10149,"journal":{"name":"Chinese Journal of Pharmacology and Toxicology","volume":"31 1","pages":"1106-1113"},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43036514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-12-01DOI: 10.3867/J.ISSN.1000-3002.2012.06.012
Chongshan Dai, Ji Chang Li, Wei Lin, Feng Wang, M. C. Sun, Jian Li
OBJECTIVE To investigate the toxic actions of colistin sulphate on sciatic-tibial nerves of mice.METHODS Colistin sulphate 7.5 mg·kg-1 was iv administered to Kunming female mice,twice a day.The mice were divided into colistin sulphate 1,3,7 d and 7 d post colistin sulphate groups according the adminstration for 1,3 and 7 d,respectively.The body mass and gait observations were obtained first,followed by determinations of foot splay and the threshold intensity(TI),maximal intensity(MI),compound action potential duration(CAPD),latency of compound action potential(CAPL),compound action potential amplitude(peak to peak)(CAPA),and nerve conduction velocity(NCV) of sciatic-tibial nerve.Serum creatinine(Cre) and urea nitrogen(BUN) concentrations were determined before the first dose on 2nd day(d 2),d 4,d 8 and d 15(the day of the first dose as the first day).RESULTS Compared with normal control group,after colistin sulphate was given for 1 d,Cre showed significant difference(P0.05);and for 3 d,BUN and body mass showed significant difference,respectively(P0.05);after colistin sulphate was given for 7 d,the gait and the foot splay showed significant difference(both P0.05).Compared with normal control group,after colistin sulphate was given for 1,3 and 7 d,TI increased by 60%,60% and 192%(P0.01),respectively;MI increased by 4%,13% and 100%(P0.05),respectively;CAPD increased by 15.1%,11.5% and 52.8%(P0.05),respectively;CAPL prolonged by 9.0%,9.0% and 14.6%(P0.05),respectively;CAPA decreased 0.92%,16.2% and 47.6%(P0.01),respectively;and NCV decreased by 7.6%,7.5% and 12.7%(P0.05),respectively.After 7 d of stopping administration,the gait and the foot splay had no significant differences,and all electrophysiology indexes showed a recovery tendency and only CAPA was significantly different(P0.05).CONCLUTION Nephrotoxicity is earlier than neurotoxicity on mice treated with colistin sulphate,at the same time,the progressive changes in CAP characteristics of the sciatic-tibial nerves are dependent with the time of colistin sulphate administration and abnormal CAPA has the longest duration time.
{"title":"Electrophysiological changes for toxic effect of colistin sulphate on sciatic-tibial nerves in mice","authors":"Chongshan Dai, Ji Chang Li, Wei Lin, Feng Wang, M. C. Sun, Jian Li","doi":"10.3867/J.ISSN.1000-3002.2012.06.012","DOIUrl":"https://doi.org/10.3867/J.ISSN.1000-3002.2012.06.012","url":null,"abstract":"OBJECTIVE To investigate the toxic actions of colistin sulphate on sciatic-tibial nerves of mice.METHODS Colistin sulphate 7.5 mg·kg-1 was iv administered to Kunming female mice,twice a day.The mice were divided into colistin sulphate 1,3,7 d and 7 d post colistin sulphate groups according the adminstration for 1,3 and 7 d,respectively.The body mass and gait observations were obtained first,followed by determinations of foot splay and the threshold intensity(TI),maximal intensity(MI),compound action potential duration(CAPD),latency of compound action potential(CAPL),compound action potential amplitude(peak to peak)(CAPA),and nerve conduction velocity(NCV) of sciatic-tibial nerve.Serum creatinine(Cre) and urea nitrogen(BUN) concentrations were determined before the first dose on 2nd day(d 2),d 4,d 8 and d 15(the day of the first dose as the first day).RESULTS Compared with normal control group,after colistin sulphate was given for 1 d,Cre showed significant difference(P0.05);and for 3 d,BUN and body mass showed significant difference,respectively(P0.05);after colistin sulphate was given for 7 d,the gait and the foot splay showed significant difference(both P0.05).Compared with normal control group,after colistin sulphate was given for 1,3 and 7 d,TI increased by 60%,60% and 192%(P0.01),respectively;MI increased by 4%,13% and 100%(P0.05),respectively;CAPD increased by 15.1%,11.5% and 52.8%(P0.05),respectively;CAPL prolonged by 9.0%,9.0% and 14.6%(P0.05),respectively;CAPA decreased 0.92%,16.2% and 47.6%(P0.01),respectively;and NCV decreased by 7.6%,7.5% and 12.7%(P0.05),respectively.After 7 d of stopping administration,the gait and the foot splay had no significant differences,and all electrophysiology indexes showed a recovery tendency and only CAPA was significantly different(P0.05).CONCLUTION Nephrotoxicity is earlier than neurotoxicity on mice treated with colistin sulphate,at the same time,the progressive changes in CAP characteristics of the sciatic-tibial nerves are dependent with the time of colistin sulphate administration and abnormal CAPA has the longest duration time.","PeriodicalId":10149,"journal":{"name":"Chinese Journal of Pharmacology and Toxicology","volume":"26 1","pages":"847-852"},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70223638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-06-01DOI: 10.3867/J.ISSN.1000-3002.2012.03.016
Yu Zhao, Junhua Wu, Pei-yuan Jia, Shaoping Wu, Shane Gao, W. Chenyu, Y. Wang
{"title":"Hepatic toxicity of TAT-P53 fusion protein in mice","authors":"Yu Zhao, Junhua Wu, Pei-yuan Jia, Shaoping Wu, Shane Gao, W. Chenyu, Y. Wang","doi":"10.3867/J.ISSN.1000-3002.2012.03.016","DOIUrl":"https://doi.org/10.3867/J.ISSN.1000-3002.2012.03.016","url":null,"abstract":"","PeriodicalId":10149,"journal":{"name":"Chinese Journal of Pharmacology and Toxicology","volume":"26 1","pages":"344-346"},"PeriodicalIF":0.0,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70223470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-06-01DOI: 10.3867/J.ISSN.1000-3002.2011.03.001
H. Wei, W. Pan, Ni Qiu, Li Huang, Hong-hao Zhou, Zhousheng Xiao
OBJECTIVE To investigate the effect of tacrolimus on cell proliferation and osteoblastic differentiation of primary human bone marrow-derived mesenchymal stem cells(hBMSCs).METHODS hBMSCs were cultured with tacrolimus 0.001-5 μmol·L-1.BrdU incorporation was used to assess the cell proliferation while cellular alkaline phosphatase(ALP) activity and calcium deposition were measured to evaluate the osteoblastic differentiation of hBMSCs cultures.The calcineurin(CaN) activity was also examined using commercial CaN assay kit,and core binding factor 1 alpha subunit(Cbfα1) protein level was determined by Western blotting.RESULTSTacrolimus 0.001-0.1 μmol·L-1 promoted BrdU incorporation but had no effect on ALP activity and calcium deposition,whereas tacrolimus 0.5-5 μmol·L-1 resulted in significant decrease in both cell proliferation and osteoblastic maturation,by reducing BrdU incorporation,ALP activity,and calcium deposition of hBMSCs cultures in a concentration-dependent manner.In addition,tacrolimus 0.5-5 μmol·L-1 led to concentration-dependent decrement in CaN activity,which was consistent with down-regulated Cbfα1 protein in the tacrolimus treated cells.CONCLUSION High concentration of tacrolimus might inhibit the cell proliferation and osteoblastic differentiation of hBMSCs cultures through a CaN/Cbfα1 pathway.
{"title":"High concentration of tacrolimus inhibits proliferation and osteoblastic differentiation of human mesenchymal stem cells","authors":"H. Wei, W. Pan, Ni Qiu, Li Huang, Hong-hao Zhou, Zhousheng Xiao","doi":"10.3867/J.ISSN.1000-3002.2011.03.001","DOIUrl":"https://doi.org/10.3867/J.ISSN.1000-3002.2011.03.001","url":null,"abstract":"OBJECTIVE To investigate the effect of tacrolimus on cell proliferation and osteoblastic differentiation of primary human bone marrow-derived mesenchymal stem cells(hBMSCs).METHODS hBMSCs were cultured with tacrolimus 0.001-5 μmol·L-1.BrdU incorporation was used to assess the cell proliferation while cellular alkaline phosphatase(ALP) activity and calcium deposition were measured to evaluate the osteoblastic differentiation of hBMSCs cultures.The calcineurin(CaN) activity was also examined using commercial CaN assay kit,and core binding factor 1 alpha subunit(Cbfα1) protein level was determined by Western blotting.RESULTSTacrolimus 0.001-0.1 μmol·L-1 promoted BrdU incorporation but had no effect on ALP activity and calcium deposition,whereas tacrolimus 0.5-5 μmol·L-1 resulted in significant decrease in both cell proliferation and osteoblastic maturation,by reducing BrdU incorporation,ALP activity,and calcium deposition of hBMSCs cultures in a concentration-dependent manner.In addition,tacrolimus 0.5-5 μmol·L-1 led to concentration-dependent decrement in CaN activity,which was consistent with down-regulated Cbfα1 protein in the tacrolimus treated cells.CONCLUSION High concentration of tacrolimus might inhibit the cell proliferation and osteoblastic differentiation of hBMSCs cultures through a CaN/Cbfα1 pathway.","PeriodicalId":10149,"journal":{"name":"Chinese Journal of Pharmacology and Toxicology","volume":"25 1","pages":"223-228"},"PeriodicalIF":0.0,"publicationDate":"2011-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70223385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-06-01DOI: 10.3867/J.ISSN.1000-3002.2009.03.013
X. Xue, Li-kun Gong, Jin Ren
It is unavoidable for body to exposure of organic anions including endogenous agents such as hormones,neurotransmitters and cellular metabolites,and xenobiotic agents such as medication,herbicides,pesticides,and plant and animal toxins. Rapid and efficient elimination of toxic substances among them is the body′s best defense. The active transepithelial transport mediated by organic anion transporters is often a rate-limiting step. Therefore,the investigations of organic anion transporters about their classification,tissue distrubution driving force,gene expression and regulatory are of great significance in toxicology.
{"title":"Role of organic anion transporters in xenobiotics induced toxicity","authors":"X. Xue, Li-kun Gong, Jin Ren","doi":"10.3867/J.ISSN.1000-3002.2009.03.013","DOIUrl":"https://doi.org/10.3867/J.ISSN.1000-3002.2009.03.013","url":null,"abstract":"It is unavoidable for body to exposure of organic anions including endogenous agents such as hormones,neurotransmitters and cellular metabolites,and xenobiotic agents such as medication,herbicides,pesticides,and plant and animal toxins. Rapid and efficient elimination of toxic substances among them is the body′s best defense. The active transepithelial transport mediated by organic anion transporters is often a rate-limiting step. Therefore,the investigations of organic anion transporters about their classification,tissue distrubution driving force,gene expression and regulatory are of great significance in toxicology.","PeriodicalId":10149,"journal":{"name":"Chinese Journal of Pharmacology and Toxicology","volume":"23 1","pages":"237-240"},"PeriodicalIF":0.0,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70223365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-06-01DOI: 10.3867/J.ISSN.1000-3002.2008.03.007
L. Yang, J. He, Wen Dong, Xin Zhang, C. Zhou, X. Ren, Weiqun Yan
AIM To observe the protection of recombinant bovine pancreatic trypsin inhibitor(rBPTI) against chronic liver injury.METHODS Ninety eight rats were randomized into 7 groups:normal control,model control,rBPTI 20,40 and 80 MU·kg-1,aprotinin 80 MU·kg-1 and hepatocyte growth-promoting factor(pHGF) 100 mg·kg-1 groups.The chronic liver injury rat model was induced by carbon tetrachloride(CCl4).After 8 weeks,the rats were administered(ip) with rBPTI,aprotinin or pHGF daily for 4 weeks except that in normal and model control groups.The glutamic-pyruvic transaminase(GPT) and glutamic-oxalacetic transaminase(GOT) activities,albumin(Alb) content,Alb and globulin content ratio(A/G),sialic acid(SA) content in serum were measured.Hydroxyproline(Hyp) level and histopathological changes of hepatic tissue were also examined.RESULTS Compared with normal control group,the activities of serum GPT and GOT,and the contents of SA in serum and Hyp in liver tissue in model group were increased,and the content of serum Alb and A/G ratio were decreased.Compared with model group,rBPTI(20,40 and 80 MU·kg-1) decreased the activities of GPT and GOT,and the contents of SA in serum and Hyp in liver tissue.The content of serum Alb and A/G ratio were increased by rBPTI.In addition,rBPTI alleviated chronic hepatic injuries such as fatty degeneration and liver fibrosis significantly.CONCLUSION rBPTI has protective and anti-fibrosis effects against chronic liver injury induced by CCl4,and the efficiency is equivalent as aprotinin in the observed dosages.
{"title":"Protective effect of recombinant bovine pancreatic trypsin inhibitor on chronic liver injury induced by carbon tetrachloride in rats","authors":"L. Yang, J. He, Wen Dong, Xin Zhang, C. Zhou, X. Ren, Weiqun Yan","doi":"10.3867/J.ISSN.1000-3002.2008.03.007","DOIUrl":"https://doi.org/10.3867/J.ISSN.1000-3002.2008.03.007","url":null,"abstract":"AIM To observe the protection of recombinant bovine pancreatic trypsin inhibitor(rBPTI) against chronic liver injury.METHODS Ninety eight rats were randomized into 7 groups:normal control,model control,rBPTI 20,40 and 80 MU·kg-1,aprotinin 80 MU·kg-1 and hepatocyte growth-promoting factor(pHGF) 100 mg·kg-1 groups.The chronic liver injury rat model was induced by carbon tetrachloride(CCl4).After 8 weeks,the rats were administered(ip) with rBPTI,aprotinin or pHGF daily for 4 weeks except that in normal and model control groups.The glutamic-pyruvic transaminase(GPT) and glutamic-oxalacetic transaminase(GOT) activities,albumin(Alb) content,Alb and globulin content ratio(A/G),sialic acid(SA) content in serum were measured.Hydroxyproline(Hyp) level and histopathological changes of hepatic tissue were also examined.RESULTS Compared with normal control group,the activities of serum GPT and GOT,and the contents of SA in serum and Hyp in liver tissue in model group were increased,and the content of serum Alb and A/G ratio were decreased.Compared with model group,rBPTI(20,40 and 80 MU·kg-1) decreased the activities of GPT and GOT,and the contents of SA in serum and Hyp in liver tissue.The content of serum Alb and A/G ratio were increased by rBPTI.In addition,rBPTI alleviated chronic hepatic injuries such as fatty degeneration and liver fibrosis significantly.CONCLUSION rBPTI has protective and anti-fibrosis effects against chronic liver injury induced by CCl4,and the efficiency is equivalent as aprotinin in the observed dosages.","PeriodicalId":10149,"journal":{"name":"Chinese Journal of Pharmacology and Toxicology","volume":"22 1","pages":"193-198"},"PeriodicalIF":0.0,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70223205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-01-01DOI: 10.3867/J.ISSN.1000-3002.2008.06.011
Q. Pan, Y. Chen, L. Mei, R. Dai
AIM To study the effect of cryopreservation on metabolic activities and cytochrome P450(CYP) mRNA expression in hepatocytes and provide support for application of cryopreserved hepatocytes in experimental research.METHODS Freshly isolated rat hepatocytes were cryopreserved with rate-controlled freezer,and thawed after 1 month.Real-time quantitative PCR was used to detect expressions of CYP1A2,CYP2B1 and CYP3A1 mRNA,and LC-MS/MS was used to measure contents of metabolites of midazolam-1′-hydrxylation(OH-Mid),diclofenac-4′-hydroxylation(OH-Dic) and dextromethorphan-O-demethylation(Dex) in hepatocytes,respectively.RESULTS There was no significant difference in cell viability between fresh and cryopreserved hepatocytes.The cryopreserved hepatocytes attached and established extensive cell-cell contact,with round and bright nucleus.CYP1A2 and CYP2B1 mRNA expressions induced by β-naphthoflavone and phenobarbital in cryopreserved hepatocytes were similar to that in the fresh primary cells.However,CYP3A1 mRNA expression did not induced by pregnenolone-16α-carbonitrile in cryopreserved hepatocytes.In cryopreserved hepatocytes,the content of OH-Mid was remained as almost the same as the fresh primary hepatocytes,while contents of OH-Dic decreased approximately as a half,and Dex was double as fresh hepatocytes.CONCLUSION Cryopreservation exerts different effects on metabolic activities of hepatocytes.To acquire objective and appropriate results,it is necessary to consider the different influence of cryopreservation on cell metabolic activity in drug metabolic research.
目的研究低温保存对肝细胞代谢活性及细胞色素P450(CYP) mRNA表达的影响，为低温保存肝细胞在实验研究中的应用提供支持。方法新鲜分离的大鼠肝细胞采用速控冷冻机冷冻保存，1个月后解冻。Real-time定量PCR检测CYP1A2、CYP2B1和CYP3A1 mRNA的表达，LC-MS/MS检测肝细胞中咪达唑仑-1′-羟基化(OH-Mid)、双氯芬酸-4′-羟基化(OH-Dic)和右美沙芬- o -去甲基化(Dex)代谢物的含量。结果新鲜肝细胞和冷冻肝细胞的细胞活力无显著差异。冷冻保存的肝细胞附着并建立了广泛的细胞间接触，细胞核圆而明亮。β-萘黄酮和苯巴比妥对低温保存肝细胞中CYP1A2和CYP2B1 mRNA表达的影响与新鲜原代细胞相似。而孕烯醇酮-16α-碳腈在低温保存的肝细胞中没有诱导CYP3A1 mRNA的表达。在冷冻保存的肝细胞中，OH-Mid的含量与新鲜原代肝细胞几乎相同，OH-Dic的含量减少了大约一半，Dex的含量是新鲜肝细胞的两倍。结论低温保存对肝细胞代谢活性有不同的影响。在药物代谢研究中，为了获得客观合理的结果，需要考虑低温保存对细胞代谢活性的不同影响。
{"title":"Effect of cryopreservation on metabolic activities of hepatocytes","authors":"Q. Pan, Y. Chen, L. Mei, R. Dai","doi":"10.3867/J.ISSN.1000-3002.2008.06.011","DOIUrl":"https://doi.org/10.3867/J.ISSN.1000-3002.2008.06.011","url":null,"abstract":"AIM To study the effect of cryopreservation on metabolic activities and cytochrome P450(CYP) mRNA expression in hepatocytes and provide support for application of cryopreserved hepatocytes in experimental research.METHODS Freshly isolated rat hepatocytes were cryopreserved with rate-controlled freezer,and thawed after 1 month.Real-time quantitative PCR was used to detect expressions of CYP1A2,CYP2B1 and CYP3A1 mRNA,and LC-MS/MS was used to measure contents of metabolites of midazolam-1′-hydrxylation(OH-Mid),diclofenac-4′-hydroxylation(OH-Dic) and dextromethorphan-O-demethylation(Dex) in hepatocytes,respectively.RESULTS There was no significant difference in cell viability between fresh and cryopreserved hepatocytes.The cryopreserved hepatocytes attached and established extensive cell-cell contact,with round and bright nucleus.CYP1A2 and CYP2B1 mRNA expressions induced by β-naphthoflavone and phenobarbital in cryopreserved hepatocytes were similar to that in the fresh primary cells.However,CYP3A1 mRNA expression did not induced by pregnenolone-16α-carbonitrile in cryopreserved hepatocytes.In cryopreserved hepatocytes,the content of OH-Mid was remained as almost the same as the fresh primary hepatocytes,while contents of OH-Dic decreased approximately as a half,and Dex was double as fresh hepatocytes.CONCLUSION Cryopreservation exerts different effects on metabolic activities of hepatocytes.To acquire objective and appropriate results,it is necessary to consider the different influence of cryopreservation on cell metabolic activity in drug metabolic research.","PeriodicalId":10149,"journal":{"name":"Chinese Journal of Pharmacology and Toxicology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70223320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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