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

Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, VIC 3083, Australia
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;
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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