This page has only limited features, please log in for full access.
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.
Priyanka Reddy; Aaron Elkins; Joanne Hemsworth; Kathryn Guthridge; Simone Vassiliadis; Elizabeth Read; German Spangenberg; Simone Rochfort. Identification and Distribution of Novel Metabolites of Lolitrem B in Mice by High-Resolution Mass Spectrometry. Molecules 2020, 25, 372 .
AMA StylePriyanka Reddy, Aaron Elkins, Joanne Hemsworth, Kathryn Guthridge, Simone Vassiliadis, Elizabeth Read, German Spangenberg, Simone Rochfort. Identification and Distribution of Novel Metabolites of Lolitrem B in Mice by High-Resolution Mass Spectrometry. Molecules. 2020; 25 (2):372.
Chicago/Turabian StylePriyanka Reddy; Aaron Elkins; Joanne Hemsworth; Kathryn Guthridge; Simone Vassiliadis; Elizabeth Read; German Spangenberg; Simone Rochfort. 2020. "Identification and Distribution of Novel Metabolites of Lolitrem B in Mice by High-Resolution Mass Spectrometry." Molecules 25, no. 2: 372.
Indole-diterpenes are an important class of chemical compounds which can be unique to different fungal species. The highly complex lolitrem compounds are confined to Epichloë species, whilst penitrem production is confined to Penicillium spp. and Aspergillus spp. These fungal species are often present in association with pasture grasses, and the indole-diterpenes produced may cause toxicity in grazing animals. In this review, we highlight the unique structural variations of indole-diterpenes that are characterised into subgroups, including paspaline, paxilline, shearinines, paspalitrems, terpendoles, penitrems, lolitrems, janthitrems, and sulpinines. A detailed description of the unique biological activities has been documented where even structurally related compounds have displayed unique biological activities. Indole-diterpene production has been reported in two classes of ascomycete fungi, namely Eurotiomycetes (e.g., Aspergillus and Penicillium) and Sordariomycetes (e.g., Claviceps and Epichloë). These compounds all have a common structural core comprised of a cyclic diterpene skeleton derived from geranylgeranyl diphosphate (GGPP) and an indole moiety derived from tryptophan. Structure diversity is generated from the enzymatic conversion of different sites on the basic indole-diterpene structure. This review highlights the wide-ranging biological versatility presented by the indole-diterpene group of compounds and their role in an agricultural and pharmaceutical setting.
Priyanka Reddy; Kathryn Guthridge; Simone Vassiliadis; Joanne Hemsworth; Inoka Hettiarachchige; German Spangenberg; Simone Rochfort. Tremorgenic Mycotoxins: Structure Diversity and Biological Activity. Toxins 2019, 11, 302 .
AMA StylePriyanka Reddy, Kathryn Guthridge, Simone Vassiliadis, Joanne Hemsworth, Inoka Hettiarachchige, German Spangenberg, Simone Rochfort. Tremorgenic Mycotoxins: Structure Diversity and Biological Activity. Toxins. 2019; 11 (5):302.
Chicago/Turabian StylePriyanka Reddy; Kathryn Guthridge; Simone Vassiliadis; Joanne Hemsworth; Inoka Hettiarachchige; German Spangenberg; Simone Rochfort. 2019. "Tremorgenic Mycotoxins: Structure Diversity and Biological Activity." Toxins 11, no. 5: 302.