P-glycoprotein and multidrug resistance-associated protein 2 are oppositely altered in brain of rats with thioacetamide-induced acute liver failure
文献类型:期刊论文
作者 | Jin, Shi1,2; Wang, Xin-Ting2; Liu, Li2; Yao, Dan3; Liu, Can2; Zhang, Mian2; Guo, Hai-Fang2; Liu, Xiao-Dong2 |
刊名 | LIVER INTERNATIONAL
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出版日期 | 2013-02 |
卷号 | 33期号:2页码:274-282 |
关键词 | Acute liver failure Brain-blood barrier multidrug resistance-associated protein 2 P-glycoprotein |
ISSN号 | 1478-3223 |
DOI | 10.1111/j.1478-3231.2012.02862.x |
文献子类 | Article |
英文摘要 | Background P-glycoprotein (P-GP) and multidrug resistance-associated protein 2 (MRP2) are involved in transport of many drugs across bloodbrain barrier (BBB). The function and expression of P-GP and MRP2 may be modulated by different pathologies. Acute liver failure (ALF) was reported to impair BBB function, resulting in the increased BBB permeability. Aims We investigated whether ALF altered function and expression of P-GP and MRP2 in brain of thioacetamide-induced ALF rats. Methods ALF was induced by intraperitoneal injection of thioacetamide (300 mg/kg) for 2 days with a 24-h interval. The rats were used for experiments at 6, 12 and 24 h after the second administration. P-GP and MRP2 function in brain were determined using the brain-to-plasma ratios of corresponding substrates (rhodamine 123 and vincristine for P-GP; sulfobromophthalein and dinitrophenyl-S-glutathione for MRP2). Evans blue was used for examining the BBB integrity. Western blot was accomplished to determine P-GP and MRP2 protein expression. Results The brain-to-plasma ratios of rhodamine 123 and vincristine were significantly increased in ALF-6 h rats and almost returned to normal levels in ALF-24 h rats, whereas those of sulfobromophthalein and dinitrophenyl-S-glutathione were decreased in all ALF rats. Western blot results showed that ALF decreased brain P-GP levels at 6 and 12 h, whereas increased MRP2 levels at 6, 12 and 24 h. No significant difference of Evans blue concentrations in brain was found among the four groups. Conclusions Function and expression of P-GP and MRP2 in brain of thioacetamide-induced ALF rats were oppositely altered. |
WOS关键词 | FULMINANT HEPATIC-FAILURE ; DRUG EFFLUX TRANSPORTERS ; NECROSIS-FACTOR-ALPHA ; OXIDATIVE STRESS ; CONJUGATED BILIRUBIN ; BARRIER PERMEABILITY ; CEREBRAL-CORTEX ; IN-VIVO ; EXPRESSION ; MRP2 |
资助项目 | National Science foundation of China[81072693] ; National Science foundation of China[30873123] ; Fund for Colleges and universities in Jiangsu province of outstanding scientific and technological innovation team[00000000] |
WOS研究方向 | Gastroenterology & Hepatology |
语种 | 英语 |
WOS记录号 | WOS:000313263000016 |
出版者 | WILEY-BLACKWELL |
源URL | [http://119.78.100.183/handle/2S10ELR8/277757] ![]() |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Liu, Xiao-Dong |
作者单位 | 1.Beijing Tsinghua Hosp, Dept Pharm, Beijing, Peoples R China; 2.China Pharmaceut Univ, Key Lab Drug Metab & Pharmacokinet, Nanjing 210009, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai 200031, Peoples R China |
推荐引用方式 GB/T 7714 | Jin, Shi,Wang, Xin-Ting,Liu, Li,et al. P-glycoprotein and multidrug resistance-associated protein 2 are oppositely altered in brain of rats with thioacetamide-induced acute liver failure[J]. LIVER INTERNATIONAL,2013,33(2):274-282. |
APA | Jin, Shi.,Wang, Xin-Ting.,Liu, Li.,Yao, Dan.,Liu, Can.,...&Liu, Xiao-Dong.(2013).P-glycoprotein and multidrug resistance-associated protein 2 are oppositely altered in brain of rats with thioacetamide-induced acute liver failure.LIVER INTERNATIONAL,33(2),274-282. |
MLA | Jin, Shi,et al."P-glycoprotein and multidrug resistance-associated protein 2 are oppositely altered in brain of rats with thioacetamide-induced acute liver failure".LIVER INTERNATIONAL 33.2(2013):274-282. |
入库方式: OAI收割
来源:上海药物研究所
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