Abstract |
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.
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Authors | Priyanka Reddy, Aaron Elkins, Joanne Hemsworth, Kathryn Guthridge, Simone Vassiliadis, Elizabeth Read, German Spangenberg, Simone Rochfort |
Journal | Molecules (Basel, Switzerland)
(Molecules)
Vol. 25
Issue 2
(Jan 16 2020)
ISSN: 1420-3049 [Electronic] Switzerland |
PMID | 31963254
(Publication Type: Journal Article)
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Chemical References |
- Indole Alkaloids
- Mycotoxins
- lolitrem B
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Topics |
- Animals
- Chromatography, Liquid
- Epichloe
(metabolism)
- Inactivation, Metabolic
- Indole Alkaloids
(metabolism)
- Mass Spectrometry
- Metabolic Detoxication, Phase I
- Metabolic Detoxication, Phase II
- Mice
- Molecular Structure
- Mycotoxins
(metabolism)
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