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Hepatocellular toxicity of kava leaf and root extracts.
Phytomedicine. 2008 Jan; 15(1-2):120-31.P

Abstract

Kava extracts are used widely for different purposes and were thought to be safe. Recently, several cases of hepatotoxicity have been published. To explore possible mechanisms of kava hepatotoxicity, we prepared and analyzed three different kava extracts (a methanolic and an acetonic root and a methanolic leaf extract), and investigated their toxicity on HepG2 cells and isolated rat liver mitochondria. All three extracts showed cytotoxicity starting at a concentration of 50 microg/ml (lactate dehydrogenase leakage) or 1 microg/ml (MTT test). The mitochondrial membrane potential was decreased (root extracts starting at 50 microg/ml) and the respiratory chain inhibited and uncoupled (root extracts) or only uncoupled (leaf extract) at 150 microg/ml, and mitochondrial beta-oxidation was inhibited by all extracts starting at 100 microg/ml. The ratio oxidized to reduced glutathione was increased in HepG2 cells, whereas the cellular ATP content was maintained. Induction of apoptosis was demonstrated by all extracts at a concentration of 150 microg/ml. These results indicate that the kava extracts are toxic to mitochondria, leading to inhibition of the respiratory chain, increased ROS production, a decrease in the mitochondrial membrane potential and eventually to apoptosis of exposed cells. In predisposed patients, mitochondrial toxicity of kava extract may explain hepatic adverse reactions of this drug.

Authors+Show Affiliations

Division of Clinical Pharmacology & Toxicology, Department of Research, University Hospital, CH-4031 Basel, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18055189

Citation

Lüde, Saskia, et al. "Hepatocellular Toxicity of Kava Leaf and Root Extracts." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 15, no. 1-2, 2008, pp. 120-31.
Lüde S, Török M, Dieterle S, et al. Hepatocellular toxicity of kava leaf and root extracts. Phytomedicine. 2008;15(1-2):120-31.
Lüde, S., Török, M., Dieterle, S., Jäggi, R., Büter, K. B., & Krähenbühl, S. (2008). Hepatocellular toxicity of kava leaf and root extracts. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 15(1-2), 120-31.
Lüde S, et al. Hepatocellular Toxicity of Kava Leaf and Root Extracts. Phytomedicine. 2008;15(1-2):120-31. PubMed PMID: 18055189.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatocellular toxicity of kava leaf and root extracts. AU - Lüde,Saskia, AU - Török,Michael, AU - Dieterle,Sandy, AU - Jäggi,René, AU - Büter,Karin Berger, AU - Krähenbühl,Stephan, Y1 - 2007/12/04/ PY - 2007/08/20/received PY - 2007/10/26/revised PY - 2007/11/12/accepted PY - 2007/12/7/pubmed PY - 2008/5/31/medline PY - 2007/12/7/entrez SP - 120 EP - 31 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 15 IS - 1-2 N2 - Kava extracts are used widely for different purposes and were thought to be safe. Recently, several cases of hepatotoxicity have been published. To explore possible mechanisms of kava hepatotoxicity, we prepared and analyzed three different kava extracts (a methanolic and an acetonic root and a methanolic leaf extract), and investigated their toxicity on HepG2 cells and isolated rat liver mitochondria. All three extracts showed cytotoxicity starting at a concentration of 50 microg/ml (lactate dehydrogenase leakage) or 1 microg/ml (MTT test). The mitochondrial membrane potential was decreased (root extracts starting at 50 microg/ml) and the respiratory chain inhibited and uncoupled (root extracts) or only uncoupled (leaf extract) at 150 microg/ml, and mitochondrial beta-oxidation was inhibited by all extracts starting at 100 microg/ml. The ratio oxidized to reduced glutathione was increased in HepG2 cells, whereas the cellular ATP content was maintained. Induction of apoptosis was demonstrated by all extracts at a concentration of 150 microg/ml. These results indicate that the kava extracts are toxic to mitochondria, leading to inhibition of the respiratory chain, increased ROS production, a decrease in the mitochondrial membrane potential and eventually to apoptosis of exposed cells. In predisposed patients, mitochondrial toxicity of kava extract may explain hepatic adverse reactions of this drug. SN - 0944-7113 UR - https://www.unboundmedicine.com/medline/citation/18055189/Hepatocellular_toxicity_of_kava_leaf_and_root_extracts_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(07)00275-9 DB - PRIME DP - Unbound Medicine ER -