NDT Advance Access originally published online on November 28, 2006
Nephrology Dialysis Transplantation 2007 22(3):732-739; doi:10.1093/ndt/gfl699
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Tetramethylpyrazine protects rat renal tubular cell apoptosis induced by gentamicin
1Department of Physiology, Taipei Medical University, 2Department of Nephrology, Taipei Medical University-Wan Fang Hospital, 3Graduate Institute of Medical Sciences, Taipei Medical University and 4Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Correspondence and offprint requests to: Yuh-Mou Sue, MD, Department of Nephrology, Taipei Medical University-Wan Fang Hospital, 5th floor, No. 111, Sec. 3, Xing-Long Road, Wen-Shan District 116, Taipei city, Taiwan. Email: sueym{at}med-assn.org.tw
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Abstract |
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Background. Gentamicin, a widely used antibiotic for the treatment of bacterial infection, can cause nephrotoxicity. Tetramethylpyrazine (TMP) is a compound purified from the rhizome of Ligusticum wallichi (Chuanxiong) and has been found to protect against ischaemia–reperfusion injury, nephritis and alcohol-induced toxicity in rat kidneys.
Methods. We used rat renal tubular cells (RTCs), NRK-52E, in this study. The cytotoxicity of gentamicin was checked with transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining, and the generation of reactive oxygen species was measured using the fluorescent probe 2,7-dichlorofluorescein. We evaluated several apoptotic parameters: cleaved caspase levels, tumour necrosis factor (TNF-
) excretion and nuclear factor Kappa B (NF-
B) activity. We also examined the TMP protective effect on gentamicin-induced apoptosis in rat kidneys.
Results. The results of this study showed that gentamicin was found to markedly induce apoptosis in NRK-52E cells in a dose-dependent manner; that TMP expressed a dose-dependent protective effect against gentamicin-induced apoptosis; that pre-treatment of the cells with 50 or 100 µM of TMP effectively decreased the reactive oxygen species formation induced by gentamicin; that TMP was found to inactivate the gentamicin-stimulated activities of caspase-3, caspase-8 and caspase-9, to inhibit gentamicin-induced release of cytochrome c, as well as to raise the expression of Bcl-xL; that TMP inhibited the gentamicin-induced TNF- excretion, and inactivated the transcription factor NF-B; and that the TMP treatment significantly reduced apoptotic injury in rat RTCs.
Conclusions. Based on the results of this study, we suggest that TMP can attenuate gentamicin-induced oxidative stress and apoptotic injury in rat RTCs, and that its character may have therapeutic potential for patients with renal diseases.
Keywords: apoptosis; gentamicin; renal tubular cell (RTC); tetramethylpyrazine (TMP)
*The authors wish it to be known that the first two authors have contributed equally to this work.
Received for publication: 19. 5.06
Accepted in revised form: 27.10.06
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