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Planta Med 2006; 72(10): 888-893
DOI: 10.1055/s-2006-946695
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Tetramethylpyrazine Attenuates Adriamycin-Induced Apoptotic Injury in Rat Renal Tubular Cells NRK-52E

Chung-Yi Cheng1 , Yuh-Mou Sue1 , Cheng-Hsien Chen1 , Chun-Cheng Hou1 , Paul Chan1 , 2 , Yen-Ling Chu1 , Tso-Hsiao Chen1 , 2 , Yung-Ho Hsu1
  • 1Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan
  • 2Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
Further Information

Publication History

Received: November 10, 2005

Accepted: May 25, 2006

Publication Date:
10 August 2006 (online)

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Abstract

Tetramethylpyrazine (TMP), a compound purified from Rhizoma Ligustici, is a widely used active ingredient in Chinese herbal medicine to treat cardiovascular diseases on account of its vasodilatory actions and antiplatelet activity. Studies have shown that TMP can remove oxygen free radicals and protect rat kidney from ischemia-reperfusion injury. In addition, adriamycin-induced nephrosis in rats is commonly used in pharmacological studies of human chronic renal diseases. Apoptosis of renal tubular cells has been reported in adriamycin-treated rats. To examine the therapeutic potential of TMP on chronic progressive renal diseases, adriamycin-induced injury in rat renal tubular cells NRK-52E has been used to monitor its protective effect. In TUNEL staining, TMP showed a dose-dependent protective effect against adriamycin-induced apoptosis in NRK-52E cells. Pretreatment of the cells with 10 or 100 µM of TMP effectively decreased the reactive oxygen species (ROS) formation induced by adriamycin, as measured in fluorescent assays. TMP was found to reduce the adriamycin-stimulated activities of caspase-3, caspase-8 and caspase-9, inhibit adriamycin-induced release of cytochrome c, and elevate the expression of Bcl-xL. TMP was also able to inhibit the death receptor signaling pathway and suppress the activation of transcription factor NF-κB in adriamycin-treated NRK-52E cells. Based on the results of this study, we suggest that TMP can attenuate adriamycin-induced oxidative stress and apoptotic injury in NRK-52E cells, and that it may have therapeutic potential for patients with renal diseases.

Abbreviations

TMP: tetramethylpyrazine

LDH: lactate dehydrogenase

ROS: reactive oxygen species

DCF: 2′,7′-dichlorofluorescein

TNF-α: tumor necrosis factor-α

TUNEL: terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling

Key words

Tetramethylpyrazine (TMP) - adriamycin - renal tubular cells - NRK-52E - apoptosis

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Yung-Ho Hsu, MD

Department of Medicine

Taipei Medical University-Wan Fang Hospital

No 111 Sing-Lung Road Sec. 3

Wen-Shan District

Taipei 116

Taiwan

Republic of China

Phone: +886-2-2930-7930 ext. 2711

Fax: +886-2-2933-4920

Email: yhhsu@tmu.edu.tw