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

Abstract

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.

Toxicological evaluation of methanol leaves extract of <i>Vernonia bipontini</i> Vatke in blood, liver and kidney tissues of mice

“…Other investigators following treatment with different agents [38][39][40][41]37,42 noted similar histopathological changes in liver. The histopathological abnormalities of liver and kidney tissues might be due to the presence of bioactive compounds (alkaloids, tannins, saponins, flavonoids, oxalate, and glycosides) 10,43,12 which are not dissolved in methanol during extraction of the plant because such histopathological abnormalities of the tissues didn`t find in aqueous leaf extract of the same species 6 .…”

Veno occlusive disease: Update on clinical management

“…It was first described in a patient who drank an infusion made with pyrrolizidine alkaloids [4,5] . Early histological abnormalities include sinusoidal congestion associated with centrilobular necrosis; later fibrous obliterative lesions in the hepatic venules occur with histological damage located to zone 3 of the acinus [6] .…”

Update on research and activities at the Centers for Disease Control and Prevention, and the Agency for Toxic Substances and Disease Registry

“…There are some reports of colorimetry and gas chromatography/mass spectrometry used to identify alkaloids in specific home remedies. These screening tests were later confirmed by observing toxicity of herbal extracts on hepatocytes in an in vitro cell culture [14]. Limitations of this type of testing include the fact that labs that can run these tests are not widely available, and that it is necessary to know what plant or other source should be investigated.…”

“…There may also be social obstacles to overcome, since some of these exposures are due to traditional herbal remedies and are not readily accepted as harmful by community members. In addition, the community itself may be hesitant or just fail to reveal these treatments to health-care workers, thereby limiting the available history from which public-health investigators can glean information [14].…”