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Inhibition by sporidesmin of hepatocyte bile acid transport
Abstract:
Exposure of isolated rat hepatocytes (approx. 2 x 10(7)--5 x 10(7) cells/10ml of incubation mixture) to 0.5 mg of the mycotoxin sporidesmin for 30--60 min at 37 degrees C produced loss of plasma-membrane microvilli with some disruption of organelle distribution in the sub-surface region. There was accompanying inhibition of [14C]cholate and [14C]taurocholate transport, but bile acid conjugation was not altered. Inhibition of cholate uptake was maximal after exposure of hepatocytes to sporidesmin for 1 min, and was not reversed by washing cells free of extracellular sporidesmin. N-Ethylmaleimide (0.1 mM) or dithiothreitol (1 mM) partially protected hepatocytes from sporidesmin inhibition of bile acid uptake. Significant protection was not given by other thiols or by zinc sulphate, cholesterol, ascorbate or alpha-tocopherol. The results are discussed in terms of sporidesmin action on cell membranes and the toxin's effect on bile secretion.
Insights
The mycotoxin sporidesmin damages rat liver cells, inhibiting bile acid transport by affecting cell membranes. Protective agents like N-Ethylmaleimide partially shield cells from this toxic effect.
Area of Science:
- Hepatology
- Toxicology
- Cell Biology
Background:
- Bile acid transport is crucial for liver function.
- Mycotoxins can disrupt cellular processes.
- Sporidesmin is a mycotoxin with potential cellular effects.
Purpose of the Study:
- To investigate the effects of the mycotoxin sporidesmin on isolated rat hepatocytes.
- To determine the impact of sporidesmin on bile acid transport.
- To explore potential protective mechanisms against sporidesmin toxicity.
Main Methods:
- Isolated rat hepatocytes were exposed to sporidesmin.
- Bile acid (cholate and taurocholate) uptake and conjugation were measured.
- Effects of protective agents (thiols, zinc sulfate, etc.) were assessed.
Main Results:
- Sporidesmin caused loss of plasma-membrane microvilli and disrupted organelle distribution.
- Bile acid transport was inhibited, but conjugation remained unaffected.
- N-Ethylmaleimide and dithiothreitol offered partial protection against sporidesmin-induced inhibition.
Conclusions:
- Sporidesmin directly affects hepatocyte cell membranes, leading to impaired bile acid transport.
- The mechanism involves disruption of membrane integrity rather than conjugation pathways.
- Specific thiol-reactive agents may offer partial protection against sporidesmin toxicity.