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Constituents in kava extracts potentially involved in hepatotoxicity: a review.
Chem Res Toxicol. 2011 Jul 18; 24(7):992-1002.CR

Abstract

Aqueous kava root preparations have been consumed in the South Pacific as an apparently safe ceremonial and cultural drink for centuries. However, several reports of hepatotoxicity have been linked to the consumption of kava extracts in Western countries, where mainly ethanolic or acetonic extracts are used. The mechanism of toxicity has not been established, although several theories have been put forward. The composition of the major constituents, the kava lactones, varies according to preparation method and species of kava plant, and thus, the toxicity of the individual lactones has been tested in order to establish whether a single lactone or a certain composition of lactones may be responsible for the increased prevalence of kava-induced hepatotoxicity in Western countries. However, no such conclusion has been made on the basis of current data. Inhibition or induction of the major metabolizing enzymes, which might result in drug interactions, has also gained attention, but ambiguous results have been reported. On the basis of the chemical structures of kava constituents, the formation of reactive metabolites has also been suggested as an explanation of toxicity. Furthermore, skin rash is a side effect in kava consumers, which may be indicative of the formation of reactive metabolites and covalent binding to skin proteins leading to immune-mediated responses. Reactive metabolites of kava lactones have been identified in vitro as glutathione (GSH) conjugates and in vivo as mercapturates excreted in urine. Addition of GSH to kava extracts has been shown to reduce cytotoxicity in vitro, which suggests the presence of inherently reactive constituents. Only a few studies have investigated the toxicity of the minor constituents present in kava extract, such as pipermethystine and the flavokavains, where some have been shown to display higher in vitro cytotoxicity than the lactones. To date, there remains no indisputable reason for the increased prevalence of kava-induced hepatotoxicity in Western countries.

Authors+Show Affiliations

Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark. lo@entomopharm.dkNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

21506562

Citation

Olsen, Line R., et al. "Constituents in Kava Extracts Potentially Involved in Hepatotoxicity: a Review." Chemical Research in Toxicology, vol. 24, no. 7, 2011, pp. 992-1002.
Olsen LR, Grillo MP, Skonberg C. Constituents in kava extracts potentially involved in hepatotoxicity: a review. Chem Res Toxicol. 2011;24(7):992-1002.
Olsen, L. R., Grillo, M. P., & Skonberg, C. (2011). Constituents in kava extracts potentially involved in hepatotoxicity: a review. Chemical Research in Toxicology, 24(7), 992-1002. https://doi.org/10.1021/tx100412m
Olsen LR, Grillo MP, Skonberg C. Constituents in Kava Extracts Potentially Involved in Hepatotoxicity: a Review. Chem Res Toxicol. 2011 Jul 18;24(7):992-1002. PubMed PMID: 21506562.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Constituents in kava extracts potentially involved in hepatotoxicity: a review. AU - Olsen,Line R, AU - Grillo,Mark P, AU - Skonberg,Christian, Y1 - 2011/05/03/ PY - 2011/4/22/entrez PY - 2011/4/22/pubmed PY - 2011/11/10/medline SP - 992 EP - 1002 JF - Chemical research in toxicology JO - Chem Res Toxicol VL - 24 IS - 7 N2 - Aqueous kava root preparations have been consumed in the South Pacific as an apparently safe ceremonial and cultural drink for centuries. However, several reports of hepatotoxicity have been linked to the consumption of kava extracts in Western countries, where mainly ethanolic or acetonic extracts are used. The mechanism of toxicity has not been established, although several theories have been put forward. The composition of the major constituents, the kava lactones, varies according to preparation method and species of kava plant, and thus, the toxicity of the individual lactones has been tested in order to establish whether a single lactone or a certain composition of lactones may be responsible for the increased prevalence of kava-induced hepatotoxicity in Western countries. However, no such conclusion has been made on the basis of current data. Inhibition or induction of the major metabolizing enzymes, which might result in drug interactions, has also gained attention, but ambiguous results have been reported. On the basis of the chemical structures of kava constituents, the formation of reactive metabolites has also been suggested as an explanation of toxicity. Furthermore, skin rash is a side effect in kava consumers, which may be indicative of the formation of reactive metabolites and covalent binding to skin proteins leading to immune-mediated responses. Reactive metabolites of kava lactones have been identified in vitro as glutathione (GSH) conjugates and in vivo as mercapturates excreted in urine. Addition of GSH to kava extracts has been shown to reduce cytotoxicity in vitro, which suggests the presence of inherently reactive constituents. Only a few studies have investigated the toxicity of the minor constituents present in kava extract, such as pipermethystine and the flavokavains, where some have been shown to display higher in vitro cytotoxicity than the lactones. To date, there remains no indisputable reason for the increased prevalence of kava-induced hepatotoxicity in Western countries. SN - 1520-5010 UR - https://www.unboundmedicine.com/medline/citation/21506562/Constituents_in_kava_extracts_potentially_involved_in_hepatotoxicity:_a_review_ L2 - https://doi.org/10.1021/tx100412m DB - PRIME DP - Unbound Medicine ER -