Abstract

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.

Original languageEnglish
Pages (from-to)732-739
Number of pages8
JournalNephrology Dialysis Transplantation
Volume22
Issue number3
DOIs
Publication statusPublished - Mar 2007

Fingerprint

Gentamicins
Apoptosis
Kidney
NF-kappa B
Reactive Oxygen Species
Wounds and Injuries
Ligusticum
Tumor Necrosis Factor-alpha
tetramethylpyrazine
Rhizome
Caspase 9
Caspase 8
Nephritis
Caspases
Transferases
Cytochromes c
Fluorescent Dyes
Bacterial Infections
Caspase 3
Oxidative Stress

Keywords

  • Apoptosis
  • Gentamicin
  • Renal tubular cell (RTC)
  • Tetramethylpyrazine (TMP)

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

@article{b958033a2af0407b874d6687d79f208f,
title = "Tetramethylpyrazine protects rat renal tubular cell apoptosis induced by gentamicin",
abstract = "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.",
keywords = "Apoptosis, Gentamicin, Renal tubular cell (RTC), Tetramethylpyrazine (TMP)",
author = "Juan, {Shu Hui} and Chen, {Cheng Hsien} and Hsu, {Yung Ho} and Hou, {Chun Cheng} and Chen, {Tso Hsiao} and Heng Lin and Chu, {Yen Ling} and Sue, {Yuh Mou}",
year = "2007",
month = "3",
doi = "10.1093/ndt/gfl699",
language = "English",
volume = "22",
pages = "732--739",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "3",

}

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

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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JF - Nephrology Dialysis Transplantation

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