Document Detail

Protective effect of green tea extract and tea polyphenols against FK506-induced cytotoxicity in renal cells.
MedLine Citation:
PMID:  16445594     Owner:  NLM     Status:  MEDLINE    
The nephrotoxicity induced by the immunosuppressive drug FK506 (tacrolimus or fujimycin), limits its usefulness in widespread application, and the underlying mechanism has not been completely understood. The primary targets of FK506 in the kidney are the proximal tubular epithelial cells. In this study, the protection of green tea extract against FK506-induced cell death of LLC-PK1 cells was investigated. FK506 caused a significant decrease in survival of the cells, but the addition of green tea extract reduced this effect in a dose-dependent manner. Treatment of the cells with 50 microM (41.1 microg/ml) FK506 induced a significant increase in annexin V-positive/propidium iodide-negative cells from 2.68 to 14.5%, whereas the addition of 6.25, 12.5, and 25 microg/ml of green tea extract caused a significant protective effect in apoptotic cells from 14.5 to 6.51, 3.20 and 3.02%, respectively. The effect of five different constituent tea polyphenols was also examined. Epigallocatechin-gallate and epigallocatechin significantly reduced FK506-induced cytotoxicity but epicatechin and catechin had no effect on cell viability. Furthermore, changes in cytochrome c release and caspase activation, which characterize apoptosis, were studied. Epigallocatechin-gallate and epigallocatechin suppressed a significant release of cytochrome c and activation of caspase-3 in FK506-treated LLC-PK1 cells.
Fumie Hisamura; Akiko Kojima-Yuasa; David Opare Kennedy; Isao Matsui-Yuasa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  98     ISSN:  1742-7835     ISO Abbreviation:  Basic Clin. Pharmacol. Toxicol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-31     Completed Date:  2006-07-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  192-6     Citation Subset:  IM    
Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan.
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MeSH Terms
Apoptosis / drug effects
Caspase 3
Caspases / metabolism
Cell Survival / drug effects
Flavonoids / pharmacology
Immunosuppressive Agents / toxicity*
Kidney / cytology,  drug effects*
LLC-PK1 Cells
Phenols / pharmacology*
Protective Agents / pharmacology*
Tacrolimus / toxicity*
Tea / chemistry
Reg. No./Substance:
0/Flavonoids; 0/Immunosuppressive Agents; 0/Phenols; 0/Protective Agents; 0/Tea; 0/polyphenols; 109581-93-3/Tacrolimus; 131258-00-9/Sunphenon; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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