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Original Paper

Cytotoxicity of Phenanthrenes Extracted from Aristolochia contorta in Human Proximal Tubular Epithelial Cell Line

Wen Y.a · Su T.a · Tang J.a · Zhang C.b · Wang X.b · Cai S.b · Li X.a

Author affiliations

aRenal Division, First Hospital, Peking University, and bDepartment of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, China

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Nephron Exp Nephrol 2006;103:e95–e102

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: March 22, 2005
Accepted: November 08, 2005
Published online: March 22, 2006
Issue release date: June 2006

Number of Print Pages: 1
Number of Figures: 7
Number of Tables: 1


eISSN: 1660-2129 (Online)

For additional information: https://www.karger.com/NEE

Abstract

Background/Aims:Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is predominantly a result of aristolochic acid I (AA-I) intoxication. However, other unidentified phytotoxins have indeed been postulated as the cause of this unique interstitial nephropathy. The purpose of this study was to investigate the cytotoxicity of other phenanthrene derivatives extracted from Aristolochia contorta in the human proximal tubular epithelial cell line HK-2. Methods: After HK-2 cells were incubated with an indicated concentration of test compounds for 24 h, cell viability was assessed by lactate dehydrogenase (LDH) leakage assay (cell membrane damage) in combination with MTT assay (metabolic capability). Cellular morphologic assessments were performed with a phase-contrast inverted microscope and transmission electron microscope. Results: In all test compounds at 5 µg/ml, AA-I, 7-methoxy-aristololactam IV and aristololactam IVa showed cytotoxic activity in HK-2 cells in both MTT assay and LDH leakage assay (p < 0.01). At high concentration (5–80 µg/ml), these three compounds caused a dose-dependent decrease in MTT reduction and a dose-dependent increase in LDH leakage compared to non-treated cells (p <0.01). In LDH leakage assay, 40 µg/ml 7-methoxy-aristololactam IV induced a 1.58-fold LDH leakage compared to AA-I at the same concentration (p < 0.01). Moreover, the IC50of these three compounds were 16.675 µg/ml for AA-I, 4.535 µg/ml for 7-methoxy-aristololactam IV, and 30.244 µg/ml for aristololactam IVa in MTT assay. The cellular morphologic assessments suggest interactions with cell membrane and intracellular structures such as lysosome and mitochondria are likely to be involved in cell injury induced by these three compounds. Conclusion: The potency of cytotoxic activity of aristololactam IVa and 7-methoxy-aristololactam IV extracted from A. contorta is similar to or even stronger than that of AA-I.

© 2006 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: March 22, 2005
Accepted: November 08, 2005
Published online: March 22, 2006
Issue release date: June 2006

Number of Print Pages: 1
Number of Figures: 7
Number of Tables: 1


eISSN: 1660-2129 (Online)

For additional information: https://www.karger.com/NEE


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