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Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats.
Toxicol Sci. 2007 May; 97(1):214-21.TS

Abstract

Kava-containing products remain popular in the United States and continue to be sold in health food stores and ethnic markets regardless of the fact that it was banned in Western countries such as Germany, France, Switzerland, Australia, and Canada, following reports of alleged hepatotoxicity. It is therefore critical to establish efficacy and verify adverse effects and/or herb-drug interactions for kava-kava (Piper methysticum). We have previously demonstrated that kava alkaloid, pipermethystine (PM), abundant in leaves and stem peelings, induces mitochondrial toxicity in human hepatoma cells, HepG2, as compared with the bioactive components, kavalactones (KL), abundant in the rhizome. The current study compared short-term toxic effects of PM in Fischer-344 (F-344) rats to acetone-water extracts of kava rhizome (KRE). Treatment of F-344 rats with PM (10 mg/kg) and KRE (100 mg/kg) for 2 weeks failed to elicit any significant changes in liver function tests or cause severe hepatic toxicity as measured by lipid peroxidation and apoptosis markers such as malondialdehyde, Bax, and Bcl-2. However, PM-treated rats demonstrated a significant increase in hepatic glutathione, cytosolic superoxide dismutase (Cu/ZnSOD), tumor necrosis factor alpha mRNA expression, and cytochrome P450 (CYP) 2E1 and 1A2, suggesting adaptation to oxidative stress and possible drug-drug interactions.

Authors+Show Affiliations

Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17329236

Citation

Lim, Steven T S., et al. "Effects of Kava Alkaloid, Pipermethystine, and Kavalactones On Oxidative Stress and Cytochrome P450 in F-344 Rats." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 97, no. 1, 2007, pp. 214-21.
Lim ST, Dragull K, Tang CS, et al. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats. Toxicol Sci. 2007;97(1):214-21.
Lim, S. T., Dragull, K., Tang, C. S., Bittenbender, H. C., Efird, J. T., & Nerurkar, P. V. (2007). Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats. Toxicological Sciences : an Official Journal of the Society of Toxicology, 97(1), 214-21.
Lim ST, et al. Effects of Kava Alkaloid, Pipermethystine, and Kavalactones On Oxidative Stress and Cytochrome P450 in F-344 Rats. Toxicol Sci. 2007;97(1):214-21. PubMed PMID: 17329236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats. AU - Lim,Steven T S, AU - Dragull,Klaus, AU - Tang,Chung-Shih, AU - Bittenbender,Harry C, AU - Efird,Jimmy T, AU - Nerurkar,Pratibha V, Y1 - 2007/02/27/ PY - 2007/3/3/pubmed PY - 2007/7/4/medline PY - 2007/3/3/entrez SP - 214 EP - 21 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 97 IS - 1 N2 - Kava-containing products remain popular in the United States and continue to be sold in health food stores and ethnic markets regardless of the fact that it was banned in Western countries such as Germany, France, Switzerland, Australia, and Canada, following reports of alleged hepatotoxicity. It is therefore critical to establish efficacy and verify adverse effects and/or herb-drug interactions for kava-kava (Piper methysticum). We have previously demonstrated that kava alkaloid, pipermethystine (PM), abundant in leaves and stem peelings, induces mitochondrial toxicity in human hepatoma cells, HepG2, as compared with the bioactive components, kavalactones (KL), abundant in the rhizome. The current study compared short-term toxic effects of PM in Fischer-344 (F-344) rats to acetone-water extracts of kava rhizome (KRE). Treatment of F-344 rats with PM (10 mg/kg) and KRE (100 mg/kg) for 2 weeks failed to elicit any significant changes in liver function tests or cause severe hepatic toxicity as measured by lipid peroxidation and apoptosis markers such as malondialdehyde, Bax, and Bcl-2. However, PM-treated rats demonstrated a significant increase in hepatic glutathione, cytosolic superoxide dismutase (Cu/ZnSOD), tumor necrosis factor alpha mRNA expression, and cytochrome P450 (CYP) 2E1 and 1A2, suggesting adaptation to oxidative stress and possible drug-drug interactions. SN - 1096-6080 UR - https://www.unboundmedicine.com/medline/citation/17329236/Effects_of_kava_alkaloid_pipermethystine_and_kavalactones_on_oxidative_stress_and_cytochrome_P450_in_F_344_rats_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfm035 DB - PRIME DP - Unbound Medicine ER -