J Clin Pathol. 2002 Sep; 55(9): 676-9.

Hepatic veno-occlusive disease as a result of a traditional remedy: confirmation of toxic pyrrolizidine alkaloids as the cause, using an in vitro technique.

Zuckerman M, Steenkamp V, Stewart MJ.

Department of Paediatrics, Coronation Hospital, University of Witwatersrand, Johannesburg, South Africa.

BACKGROUND/AIMS: A child presented with hepatic veno-occlusive disease after having been administered a short course of treatment with a traditional herbal remedy. The child subsequently died. Postmortem liver histology confirmed the diagnosis. This study aimed to investigate the hypothesis that the herbal remedy was the cause of veno-occlusive disease. METHODS: Extracts of the traditional remedy were analysed by colorimetry and gas chromatography/mass spectrometry. Cultured hepatocytes were treated with an extract of the plant material and examined for morphological changes. RESULTS: The screening analyses indicated the presence of toxic pyrrolizidine alkaloids, which were later confirmed by gas chromatography/mass spectrometry. The cell studies indicated dose related toxicity, with necrosis at high concentrations and apoptosis and abnormalities of the cytoskeleton at lower concentrations. CONCLUSIONS: The simple screening techniques used allowed rapid confirmation of the presence of toxic pyrrolizidines in the remedy. The in vitro method confirmed the toxicity of herbal extracts to hepatocytes.