Inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine-induced chronic nephrotoxicity

• Published in: Chinese medical journal Vol. 116; no. 9; pp. 1345 - 1350
• Main Author: 施邵华 郑树森 朱有法 贾长库 谢海洋
• Format: Journal Article
• Language: English
• Published: China Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310003, China%Department of pathology, Medical College of Zhejiang University, Zhejiang University Hangzhou 310003, China%Institute of Surgery, Zhejiang University Hangzhou 310003, China 01.09.2003
• Subjects: Animals; Apoptosis - drug effects; Cyclosporine - adverse effects; Flavonoids - pharmacology; Kidney - pathology; Kidney Diseases - chemically induced; Male; Phenols - pharmacology; Polyphenols; Rats; Rats, Sprague-Dawley; Tea; 免疫抑制剂; 慢性肾脏疾病; 环孢霉素; 细胞凋亡; 茶多酚; plant extrant; rat; drug toxicity; folium thea; kidney diseases; apoptosis; immunosupressive agents; inhibitory agents
• ISSN: 0366-6999; 2542-5641

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 thepossible 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 comparision with animals treated by CsA, animals treated with CsA plus tea polyphenols demonstratedsignificantly improved levels of creatinine clearance (0. 12±0.03 vs 0.22±0.02 ml·min^-1 . 100g^-1body 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 intubular 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).Conclusion 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.