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Inhibitory effect of tea polyphenols on transforming growth factor-beta1 expression in rat with cyclosporine
Shao-Hua Shi1, Shu-Sen Zheng, Chang-Ku Jia
1Department of Hepatobiliary Surgery, the First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China.
Aim:
To investigate the inhibitory effect of tea polyphenols (TP) on the transforming growth factor-beta1 (TGF-beta1) expression in rat model of cyclosporine A (CsA)-induced chronic nephrotoxicity.
Methods:
The rat model of CsA-induced chronic nephrotoxicity was used, 4 groups of rats were respectively treated with vehicle (0.1 mL/kg/d sc), TP (80 mg/kg/d ig), CsA (15 mg/kg/d sc) and TP plus CsA (CsA 15 mg/kg/d sc+TP 80 mg/kg/d, ig). At the end of day 28 of treatment, serum and urine are analyzed for creatinine clearance, kidney tissue for pathologic analysis. The TGF-beta1 mRNA and its protein expression were detected by RT-PCR, immunohistochemistry, and Western blot.
Results:
CsA-treated rats had increased renal expression of TGF-beta1 mRNA and its protein, compared with the vehicle- or TP-treated controls. The renal function and interstitial fibrosis were ameliorated and renal expression of TGF-beta1 mRNA and its protein was decreased in animals treated with CsA plus TP, compared with animals treated with CsA alone (P<0.05).
Conclusion:
TP significantly inhibits renal expression of TGF-beta1 in rat model of cyclosporine-induced chronic nephrotoxicity, suggesting that the decreased renal expression of TGF-beta1 exerted by TP is one of mechanisms to protect renal function and tissue structure.
Insights
Tea polyphenols (TP) reduce kidney damage from cyclosporine A (CsA) by inhibiting transforming growth factor-beta1 (TGF-beta1) expression. This suggests TP protects renal function and structure in CsA-induced nephrotoxicity.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Cyclosporine A (CsA) is a common immunosuppressant.
- CsA can cause chronic nephrotoxicity.
- Transforming growth factor-beta1 (TGF-beta1) is implicated in kidney damage.
Purpose of the Study:
- To investigate the inhibitory effect of tea polyphenols (TP) on TGF-beta1 expression.
- To evaluate TP's protective effects in a rat model of CsA-induced chronic nephrotoxicity.
Main Methods:
- A rat model of CsA-induced chronic nephrotoxicity was established.
- Rats were treated with vehicle, TP, CsA, or TP plus CsA.
- Renal function, pathology, and TGF-beta1 expression (mRNA and protein) were assessed.
Main Results:
- CsA treatment increased renal TGF-beta1 expression.
- TP treatment alone did not significantly affect TGF-beta1.
- Combined TP and CsA treatment reduced renal TGF-beta1 expression and ameliorated renal function and fibrosis compared to CsA alone.
Conclusions:
- Tea polyphenols significantly inhibit renal TGF-beta1 expression in CsA-induced nephrotoxicity.
- Reduced TGF-beta1 expression is a key mechanism by which TP protects renal function and structure.
- TP shows potential as a therapeutic agent to mitigate CsA-induced kidney damage.
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