Synergistic effect of green tea polyphenols on their protection against FK506-induced cytotoxicity in renal cells.
FK506 (tacrolimus) is a widely used immunosuppressant first employed in the management of rejection in organ transplantation, but now used for autoimmune disease. However, the nephrotoxicity induced by FK506 remains a serious clinical problem. We previously demonstrated that FK506 caused a significant increase in apoptosis of LLC-PK1 cells, a porcine proximal tubule cell line, but the addition of green tea extract and its polyphenolic components suppressed the cell death. Here, we examined the synergistic effect of tea polyphenols on the protection of FK506-induced cell death. The combined treatment with 5 microM (-)-epigallocatechin-gallate (EGCG) and 5 microM of (+)-catechin (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC) or (-)-epicatechin-gallate (ECG) reduced FK506-induced cytotoxicity in LLC-PK1. Similarly, the combined treatment with 5 microM EGC and 5 microM of C, EC, EGCG or ECG also reduced the cytotoxicity. These results showed that the co-treatments with EGCG and EGC, EGCG or ECG, and EGC and ECG have stronger synergistic effects on the protection of FK506-induced cell death. Furthermore, the combined treatment of EGCG (5 microM) and EGC (5 microM) showed a significant time-dependent suppression of the increased intracellular ROS levels 15 min after the addition of FK506, as well as on caspase activation. The results of these synergistic effects of the constituents of green tea extract suggest that its protective effects may reside in more than just one of its constituent.
Hisamura
Fumie
F
Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Osaka 558-8585, Japan.
Kojima-Yuasa
Akiko
A
Huang
Xuedan
X
Kennedy
David Opare
DO
Matsui-Yuasa
Isao
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001628:Beverages; D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D016559:Tacrolimus / Q000009:adverse effects / Q000494:pharmacology*
D005419:Flavonoids; D007166:Immunosuppressive Agents; D010636:Phenols; D059808:Polyphenols; D017382:Reactive Oxygen Species; D002392:Catechin; C045651:epigallocatechin gallate; D053148:Caspase 3; C057580:gallocatechol; D016559:Tacrolimus