Skip Navigation



ToxSci Advance Access published online on January 21, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh067
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
79/1/106    most recent
kfh067v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Nerurkar, P. V.
Right arrow Articles by Tang, C.-S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nerurkar, P. V.
Right arrow Articles by Tang, C.-S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received November 18, 2003; accepted December 30, 2003
© 2004 Society of Toxicology

In Vitro Toxicology and Alternative Testing

In Vitro Toxicity of Kava Alkaloid, Pipermethystine, in HepG2 Cells as Compared to Kavalactones

Pratibha V. Nerurkar 1*, Klaus Dragull 1, and Chung-Shih Tang 1

1 Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawaii at Manoa, Honolulu, HI 96822

* To whom correspondence should be addressed. E-mail: pratibha{at}hawaii.edu.


  Abstract

Kava herbal supplements have been recently associated with acute hepatotoxicity, leading to the ban of kava products in approximately a dozen countries around the world. It is suspected that some alkaloids from aerial kava may have contributed to the problem. Traditionally, Pacific Islanders employ primarily the underground parts of the shrub to prepare the kava beverage. However, some kava herbal supplements may contain ingredients from aerial stem peelings. The aim of this project was to test the in vitro effects of a major kava alkaloid, pipermethystine (PM) found mostly in leaves and stem peelings and kavalactones such as 7,8-dihydromethysticin (DHM), desmethoxyyangonin (DMY) that are abundant in the roots. Exposure of human hepatoma cells, HepG2, to 100 µM of PM caused 90% loss in cell viability within 24 h, while 50 µM caused 65% cell death. Similar concentrations of kavalactones did not affect cell viability up to 8 days of treatment. Mechanistic studies indicate that in contrast to kavalactones, PM significantly decreased cellular ATP levels, mitochondrial membrane potential and induced apoptosis as measured by the release of caspase-3 after 24 h of treatment. These observations suggest that PM, rather than kavalactones, is capable of causing cell death, probably in part by disrupting mitochondrial function. Thus, PM may contribute to rare but severe hepatotoxic reactions to kava.

Key Words: Piper methysticum, kava, kavalactones, 7,8-dihydromethysticin, desmethoxyyangonin, pipermethystine, apoptosis .


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Prevention ResearchHome page
T. E. Johnson, F. Kassie, M. G. O'Sullivan, M. Negia, T. E. Hanson, P. Upadhyaya, P. P. Ruvolo, S. S. Hecht, and C. Xing
Chemopreventive Effect of Kava on 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone plus Benzo[a]pyrene-Induced Lung Tumorigenesis in A/J Mice
Cancer Prevention Research, November 1, 2008; 1(6): 430 - 438.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. J. Wruck, M. E. Gotz, T. Herdegen, D. Varoga, L.-O. Brandenburg, and T. Pufe
Kavalactones Protect Neural Cells against Amyloid {beta} Peptide-Induced Neurotoxicity via Extracellular Signal-Regulated Kinase 1/2-Dependent Nuclear Factor Erythroid 2-Related Factor 2 Activation
Mol. Pharmacol., June 1, 2008; 73(6): 1785 - 1795.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S. T.S. Lim, K. Dragull, C.-S. Tang, H. C. Bittenbender, J. T. Efird, and P. V. Nerurkar
Effects of Kava Alkaloid, Pipermethystine, and Kavalactones on Oxidative Stress and Cytochrome P450 in F-344 Rats
Toxicol. Sci., May 1, 2007; 97(1): 214 - 221.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
E. J. Buenz
A BRIEF COMMUNICATION: Hepatocytes Detoxify Atuna racemosa Extract
Experimental Biology and Medicine, December 1, 2006; 231(11): 1739 - 1743.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
J. M. Mathews, A. S. Etheridge, J. L. Valentine, S. R. Black, D. P. Coleman, P. Patel, J. So, and L. T. Burka
PHARMACOKINETICS AND DISPOSITION OF THE KAVALACTONE KAWAIN: INTERACTION WITH KAVA EXTRACT AND KAVALACTONES IN VIVO AND IN VITRO
Drug Metab. Dispos., October 1, 2005; 33(10): 1555 - 1563.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.