Inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine-induced chronic nephrotoxicity.
OBJECTIVE
To investigate the inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine A (CsA)-induced chronic nephrotoxicity.


METHODS
Four groups of rats with CsA-induced chronic nephrotoxicity were respectively treated with vehicle olive oil, tea polyphenols, CsA and tea polyphenols plus CsA. At the end of the 28th day of treatment, 24 hours urine and blood samples were obtained, and the animals were then sacrificed. The serum and urine samples were analysed for creatinine clearance, and kidney tissue was used for pathologic analysis of renal tubular injury and interstitial fibrosis. The TUNEL assay, apoptosis-related enzyme caspase-3 mRNA detected by RT-PCR, and its enzymatic activity were analysed for the possible detections of cell apoptosis.


RESULTS
CsA-treated rats displayed increased apoptosis of the tubular and interstitial cells, in comparison with vehicle-treated controls (18.3 +/- 4.6 vs 4.8 +/- 1.3 cells/mm(2), P < 0.05). In comparison with animals treated by CsA, animals treated with CsA plus tea polyphenols demonstrated significantly improved levels of creatinine clearance (0.12 +/- 0.03 vs 0.22 +/- 0.02 ml.min(-1).100 g(-1) body weight, P < 0.05), tubular injury (2.29 +/- 0.43 vs 1.42 +/- 0.26, P < 0.05), and interstitial fibrosis (2.83 +/- 0.20 vs 1.46 +/- 0.19, P < 0.05), and showed a statistically significant decrease in tubular and interstitial cell apoptosis (18.3 +/- 4.6 vs 7.7 +/- 2.1 cells/mm(2), P < 0.05). The expression of caspase-3 mRNA and caspase-3 activity was significantly higher in the CsA-treated group than that of the CsA plus tea polyphenols (TP)-treated group (P < 0.05).


CONCLUSIONS
These results suggested that tea polyphenols significantly inhibits apoptosis of the tubular and interstitial cells in rats with cyclosporine-induced chronic nephrotoxicity, and that tea polyphenols may be useful to prevent CsA-associated kidney toxicity.
Shi
Shaohua
S
Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310003, China. jqj9234@sohu.com
Zheng
Shusen
S
Zhu
Youfa
Y
Jia
Changku
C
Xie
Haiyang
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016572:Cyclosporine / Q000009:adverse effects*; D005419:Flavonoids / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D013662:Tea
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D016572:Cyclosporine