TY - JOUR
T1 - Tetramethylpyrazine protects rat renal tubular cell apoptosis induced by gentamicin
AU - Juan, Shu Hui
AU - Chen, Cheng Hsien
AU - Hsu, Yung Ho
AU - Hou, Chun Cheng
AU - Chen, Tso Hsiao
AU - Lin, Heng
AU - Chu, Yen Ling
AU - Sue, Yuh Mou
N1 - Funding Information:
Acknowledgements. This study was sponsored by the Taipei Medical University-Wan Fang Hospital (95TMU-WFH-12). Prof. Winston W. Shen gave valuable editing comments on an earlier version of this manuscript.
PY - 2007/3
Y1 - 2007/3
N2 - 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 - eperfusion 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-α) excretion and nuclear factor Kappa B (NF-κB) 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-α excretion, and inactivated the transcription factor NF-κB; 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.
AB - 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 - eperfusion 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-α) excretion and nuclear factor Kappa B (NF-κB) 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-α excretion, and inactivated the transcription factor NF-κB; 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.
KW - Apoptosis
KW - Gentamicin
KW - Renal tubular cell (RTC)
KW - Tetramethylpyrazine (TMP)
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U2 - 10.1093/ndt/gfl699
DO - 10.1093/ndt/gfl699
M3 - Article
C2 - 17132701
AN - SCOPUS:33847643600
VL - 22
SP - 732
EP - 739
JO - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
JF - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
SN - 0931-0509
IS - 3
ER -