kavain and Chemical-and-Drug-Induced-Liver-Injury

In recent years, Kava kava (Piper methysticum, Forst. f., Piperaceae), a folkloric beverage and popular herbal remedy, has been implicated in a number of liver failure cases. Many hypotheses as to the mechanism of its hepatotoxicity, for example interactions with other co-ingested medication, have been postulated. This present study investigated whether pharmacokinetic interactions between kava constituents and alcohol via alcohol dehydrogenase (ADH) inhibition by individual kavalactones might explain its claimed hepatotoxic effects. Four kavalactones, (+/-)-kavain, methysticin, yangonin and desmethoxyyangonin, fail to inhibit ADH in vitro at 1, 10 or 100 microM concentrations.

Topics: Alcohol Dehydrogenase; Alcohol Drinking; Chemical and Drug Induced Liver Injury; Herb-Drug Interactions; Kava; Lactones; Plant Extracts; Pyrans; Pyrazoles; Pyrones; Spectrophotometry

Topics: Chemical and Drug Induced Liver Injury; Hepatitis, Autoimmune; Humans; Hypericum; Kava; Plant Preparations; Pyrones

Kava-kava is a traditional beverage of the South Pacific islanders and has had centuries of use without major side effects. Standardised extracts of kava-kava produced in Europe have led to many serious health problems and even to death. The extraction process (aqueous vs. acetone in the two types of preparations) is responsible for the difference in toxicity as extraction of glutathione in addition to the kava lactones is important to provide protection against hepatotoxicity. The Michael reaction between glutathione and kava lactones, resulting in opening of the lactone ring, reduces the side effects of the kava kava extracts. This protective activity was demonstrated using Acanthamoebae castellanii in which 100% cell death occurred with 100 mg ml(-1) kava lactones alone, and 40% cell death with a mixture of 100 mg ml (-1)glutathione and 100 mg ml (-1) kava lactones. A comparison of kava lactone toxicity with other pharmaceutical products is discussed and recommendations made for safe usage of kava-kava products

Topics: Acanthamoeba; Animals; Cell Survival; Chemical and Drug Induced Liver Injury; Drug Interactions; Glutathione; Humans; Kava; Lactones; Plant Extracts; Plant Roots; Plant Stems; Pyrones; Tissue Distribution

Increasing numbers of articles on adverse drug reactions are published in a wide range of medical journals. To help keep you up-to-date with the latest advances worldwide on all aspects of adverse drug reactions, this section of the journal brings you information selected from the drug safety alerting service Reactions Weekly. The following reports are selected from the latest issues, summarizing the most important clinical studies, adverse reaction news, and expert opinion pieces published across a broad range of literature sources.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Bupropion; Chemical and Drug Induced Liver Injury; Contraindications; Cyclooxygenase Inhibitors; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Interferon alpha-2; Interferon-alpha; Male; Pyrones; Recombinant Proteins; Reye Syndrome; United States; United States Food and Drug Administration