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Open AccessArticle

Identification and Distribution of Novel Metabolites of Lolitrem B in Mice by High-Resolution Mass Spectrometry

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Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, VIC 3083, Australia
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School of Applied Systems Biology, La Trobe University, Bundoora, VIC 3083, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Terenzio Bertuzzi
Molecules 2020, 25(2), 372; https://doi.org/10.3390/molecules25020372
Received: 23 December 2019 / Revised: 9 January 2020 / Accepted: 15 January 2020 / Published: 16 January 2020
(This article belongs to the Special Issue Analytical Methods for Mycotoxin Analysis)
Lolitrem B is the most potent indole-diterpene mycotoxin produced by Epichloë festucae var. lolii (termed LpTG-1), with severe intoxication cases reported in livestock. To date, there are no in vivo metabolism studies conducted for the mycotoxin. A mouse model assay established for assessing toxicity of indole-diterpenes was used to investigate metabolic products of lolitrem B. Mice were administered lolitrem B at 0.5 and 2.0 mg/kg body weight (b.wt) intraperitoneally before body and brain tissues were collected at 6 h and 24 h post-treatment. Samples were cryoground and subjected to a biphasic or monophasic extraction. The aqueous and lipophilic phases were analysed using liquid chromatography high-resolution mass spectrometry (LC–HRMS); data analysis was performed with Compound Discoverer™ software. A total of 10 novel phase I metabolic products were identified in the lipophilic phase and their distribution in the liver, kidney and various brain regions are described. The biotransformation products of lolitrem B were found to be present in low levels in the brain. Based on structure–activity postulations, six of these may contribute towards the protracted tremors exhibited by lolitrem B-exposed animals. View Full-Text
Keywords: lolitrem B; metabolism; mycotoxin; endophyte lolitrem B; metabolism; mycotoxin; endophyte
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Reddy, P.; Elkins, A.; Hemsworth, J.; Guthridge, K.; Vassiliadis, S.; Read, E.; Spangenberg, G.; Rochfort, S. Identification and Distribution of Novel Metabolites of Lolitrem B in Mice by High-Resolution Mass Spectrometry. Molecules 2020, 25, 372.

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