Protective Effect of Green Tea Extract and Tea Polyphenols against FK506‐Induced Cytotoxicity in Renal Cells

Abstract

Abstract: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 mM (41.1 mg/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 mg/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.

Inhibition property of green tea extract in relation to reserpine-induced ribosomal strips of rough endoplasmic reticulum (rER) of the rat kidney proximal tubule cells

“…Its antioxidant properties help scavenge the destructive free radicals in the body (Yoko and Santosh, 2005). Recent studies suggest that green tea has positive effects on several body organs in laboratory animals (Hisamura et al, 2006;Adhami and Mukhtar, 2007;Asfar et al, 2007;Safer et al, 2007;Khan et al, 2007;Al-Bloushi et al, 2009). The effects of which have been well-documented when used for the purpose of tissue damage recovery (Adhami and Mukhtar, 2007;Asfar et al, 2007;Safer et al, 2007;Al-Bloushi et al, 2009), or when synergistically used with cofactors like CoQ9 in rats in lowering LDL-Cholesterol (Upaganlawar et al, 2006;Afzal et al, 2007).…”

Protective effect of Korean red ginseng against FK-506-induced damage in LLC-PK1 cells

“…KIM-1 is a type I transmembranous protein that can be exploited as a sensitive biomarker of FK506-induced nephrotoxicity in rat proximal tubule epithelial cells [4]. FK506 also causes a significant increase in apoptosis of LLC-PK1 cells through a release of cytochrome c and activation of caspase-3 [7,9].…”

“…In the study about the protective effects of green tea extract and tea polyphenols against FK506-induced cytotoxicity, treatment of the cells with 50mM FK506 induced a significant increase in apoptotic cell death as demonstrated by Annexin V binding from 2.6% to 14.5% in LLC-PK1 cells [7]. To explore whether KRG could decrease FK506-induced apoptosis in LLC-PK1 cells through Annexin V Alexa Fluor 488 and propidium iodide staining, LLC-PK1 cells were treated with we treated with 10 mg/mL KRG or 50 mg/mL KRG.…”

“…Production of nitric oxide (NO), superoxide dismutase, and catalase are significantly suppressed by green tea extract in mice and LLC-PK1 cells treated with FK506 [7,8]. Polyphenols found in green tea significantly reduce FK506-induced cytotoxicity by suppressing the release of cytochrome c, activating caspase-3 and suppressing increased intracellular levels of reactive oxygen species (ROS) [7,9]. Considering the gravity of the problem, few studies have examined how best to minimize FK506-induced nephrotoxicity.…”

Flavonoid conjugates interact with organic anion transporters (OATs) and attenuate cytotoxicity of adefovir mediated by organic anion transporter 1 (OAT1/SLC22A6)

“…Lin et al [44] also reported that the flavonoid morin protected against imipenem-induced nephrotoxicity, via the inhibition of OAT3-mediated accumulation of this antibiotic. Alternatively, flavonoids may attenuate drug-induced renal damage via free radical scavenging [45,46] or anti-apoptotic M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 mechanisms [47]. Nevertheless, OAT1 and OAT3 may play an active role in these protective effects by mediating the entry of flavonoids and their metabolites into the proximal tubule cells.…”