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Review article

The cellular and molecular toxicity of sporidesmin

Pages 203-213 | Received 28 Aug 2019, Accepted 04 Feb 2020, Published online: 19 Apr 2020
 

ABSTRACT

The fungal metabolite sporidesmin is responsible for the hepatogenous photosensitising disease facial eczema in livestock. Toxicity is due to a sulfur-bridged epidithiodioxopiperazine ring that has wide biological reactivity. The ways in which the toxin causes hepatobiliary and other tissue damage have not been established. Hypotheses include direct interaction with cellular thiols including protein cysteine residues or production of reactive oxygen species resulting in oxidative stress. Comparison with the cellular effects of the structurally related compound gliotoxin suggests additional mechanisms including interaction with cell adhesion complexes and possible downstream consequences for regulated necrosis as a response to tissue injury. Revision of hypotheses of how sporidesmin affects cells has the potential to generate new strategies for control of facial eczema including through identification of proteins and genes that are associated with resistance to the disease.

Acknowledgement

The assistance of Dr Paul Teesdale-Spittle for production of Figure 1 is gratefully acknowledged.

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