Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B

Research output: Other contribution to conferencePoster

Abstract

Lolitrem B is an indole diterpenoid toxin found in perennial ryegrass. Although lolitrem B confers beneficial effects to the plant, these are counteracted by adverse effects observed animals that ingest it which can result in behavioural changes, ataxia and tremor and, in the most severe cases, seizures and death (Tor-Agbidye et al 2001). Morbidity and mortality of livestock can be in significant numbers (Cunningham 1959, Combs et al, 2014). Currently no therapeutic treatment is available that can be delivered at a flock-wide level to mitigate the large-scale effects observed in animals during critical outbreaks. Platforms for drug testing have been difficult to establish due to seasonal variations in lolitrem B in pasture-based feeds and the difficulty in extracting this highly lipophilic toxin (Munday-Finch, 1997). To overcome this, a reproducible and reliable model of PRGT in sheep was established utilizing a feed containing high levels lolitrem B toxin. This model was compared to a rodent model where animals were exposed to pure lolitrem B toxin isolated from perennial ryegrass. Establishment of these model systems allowed a number of therapeutics to be trialled. The most significant improvements were observed in movement, behaviour and reduction of stress by administration of potassium bromide. Pharmaceutical products that could improve clinical outcomes, reduce mortality can now be tested using this experimental model. This study also shows that lolitrem B induces activation of stress pathways in the brain and identified a clear role for this toxin in for testing of pharmaceutics with anxiolytic activity.
Original languageEnglish
Pages109-110
Number of pages2
Publication statusPublished - 2016
Event36th Annual Meeting of the Australasian Neuroscience Society: ANS 2016 - Hotel Grand Chancellor Hobart, Hobart, Australia
Duration: 04 Dec 201607 Dec 2016
http://aomevents.com/ANS2016 (Conference website)
https://www.ans.org.au/resources/past-ans-conferences/57-past-ans-conferences (Link to conference abstracts and posters)

Conference

Conference36th Annual Meeting of the Australasian Neuroscience Society
Abbreviated titleNeuroscience
CountryAustralia
CityHobart
Period04/12/1607/12/16
Internet address

Fingerprint

potassium bromide
indoles
diterpenoids
poisoning
toxins
Lolium perenne
drugs
Anthoxanthum
tranquilizers
therapeutics
seizures
morbidity
animals
flocks
rodents
livestock
animal models
seasonal variation
adverse effects
testing

Cite this

Combs, M. A., Edwards, S., Kessell, A. E., Hamlin, A., Scherpenhuizen, J., Narayan, E., & Quinn, J. (2016). Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B. 109-110. Poster session presented at 36th Annual Meeting of the Australasian Neuroscience Society, Hobart, Australia.
Combs, Martin A. ; Edwards, Scott ; Kessell, Allan E. ; Hamlin, Adam ; Scherpenhuizen, Joshua ; Narayan, Edward ; Quinn, Jane. / Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B. Poster session presented at 36th Annual Meeting of the Australasian Neuroscience Society, Hobart, Australia.2 p.
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title = "Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B",
abstract = "Lolitrem B is an indole diterpenoid toxin found in perennial ryegrass. Although lolitrem B confers beneficial effects to the plant, these are counteracted by adverse effects observed animals that ingest it which can result in behavioural changes, ataxia and tremor and, in the most severe cases, seizures and death (Tor-Agbidye et al 2001). Morbidity and mortality of livestock can be in significant numbers (Cunningham 1959, Combs et al, 2014). Currently no therapeutic treatment is available that can be delivered at a flock-wide level to mitigate the large-scale effects observed in animals during critical outbreaks. Platforms for drug testing have been difficult to establish due to seasonal variations in lolitrem B in pasture-based feeds and the difficulty in extracting this highly lipophilic toxin (Munday-Finch, 1997). To overcome this, a reproducible and reliable model of PRGT in sheep was established utilizing a feed containing high levels lolitrem B toxin. This model was compared to a rodent model where animals were exposed to pure lolitrem B toxin isolated from perennial ryegrass. Establishment of these model systems allowed a number of therapeutics to be trialled. The most significant improvements were observed in movement, behaviour and reduction of stress by administration of potassium bromide. Pharmaceutical products that could improve clinical outcomes, reduce mortality can now be tested using this experimental model. This study also shows that lolitrem B induces activation of stress pathways in the brain and identified a clear role for this toxin in for testing of pharmaceutics with anxiolytic activity.",
keywords = "lolitrem B, mouse",
author = "Combs, {Martin A.} and Scott Edwards and Kessell, {Allan E.} and Adam Hamlin and Joshua Scherpenhuizen and Edward Narayan and Jane Quinn",
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note = "36th Annual Meeting of the Australasian Neuroscience Society : ANS 2016, Neuroscience ; Conference date: 04-12-2016 Through 07-12-2016",
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Combs, MA, Edwards, S, Kessell, AE, Hamlin, A, Scherpenhuizen, J, Narayan, E & Quinn, J 2016, 'Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B' 36th Annual Meeting of the Australasian Neuroscience Society, Hobart, Australia, 04/12/16 - 07/12/16, pp. 109-110.

Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B. / Combs, Martin A.; Edwards, Scott; Kessell, Allan E.; Hamlin, Adam; Scherpenhuizen, Joshua; Narayan, Edward; Quinn, Jane.

2016. 109-110 Poster session presented at 36th Annual Meeting of the Australasian Neuroscience Society, Hobart, Australia.

Research output: Other contribution to conferencePoster

TY - CONF

T1 - Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B

AU - Combs, Martin A.

AU - Edwards, Scott

AU - Kessell, Allan E.

AU - Hamlin, Adam

AU - Scherpenhuizen, Joshua

AU - Narayan, Edward

AU - Quinn, Jane

PY - 2016

Y1 - 2016

N2 - Lolitrem B is an indole diterpenoid toxin found in perennial ryegrass. Although lolitrem B confers beneficial effects to the plant, these are counteracted by adverse effects observed animals that ingest it which can result in behavioural changes, ataxia and tremor and, in the most severe cases, seizures and death (Tor-Agbidye et al 2001). Morbidity and mortality of livestock can be in significant numbers (Cunningham 1959, Combs et al, 2014). Currently no therapeutic treatment is available that can be delivered at a flock-wide level to mitigate the large-scale effects observed in animals during critical outbreaks. Platforms for drug testing have been difficult to establish due to seasonal variations in lolitrem B in pasture-based feeds and the difficulty in extracting this highly lipophilic toxin (Munday-Finch, 1997). To overcome this, a reproducible and reliable model of PRGT in sheep was established utilizing a feed containing high levels lolitrem B toxin. This model was compared to a rodent model where animals were exposed to pure lolitrem B toxin isolated from perennial ryegrass. Establishment of these model systems allowed a number of therapeutics to be trialled. The most significant improvements were observed in movement, behaviour and reduction of stress by administration of potassium bromide. Pharmaceutical products that could improve clinical outcomes, reduce mortality can now be tested using this experimental model. This study also shows that lolitrem B induces activation of stress pathways in the brain and identified a clear role for this toxin in for testing of pharmaceutics with anxiolytic activity.

AB - Lolitrem B is an indole diterpenoid toxin found in perennial ryegrass. Although lolitrem B confers beneficial effects to the plant, these are counteracted by adverse effects observed animals that ingest it which can result in behavioural changes, ataxia and tremor and, in the most severe cases, seizures and death (Tor-Agbidye et al 2001). Morbidity and mortality of livestock can be in significant numbers (Cunningham 1959, Combs et al, 2014). Currently no therapeutic treatment is available that can be delivered at a flock-wide level to mitigate the large-scale effects observed in animals during critical outbreaks. Platforms for drug testing have been difficult to establish due to seasonal variations in lolitrem B in pasture-based feeds and the difficulty in extracting this highly lipophilic toxin (Munday-Finch, 1997). To overcome this, a reproducible and reliable model of PRGT in sheep was established utilizing a feed containing high levels lolitrem B toxin. This model was compared to a rodent model where animals were exposed to pure lolitrem B toxin isolated from perennial ryegrass. Establishment of these model systems allowed a number of therapeutics to be trialled. The most significant improvements were observed in movement, behaviour and reduction of stress by administration of potassium bromide. Pharmaceutical products that could improve clinical outcomes, reduce mortality can now be tested using this experimental model. This study also shows that lolitrem B induces activation of stress pathways in the brain and identified a clear role for this toxin in for testing of pharmaceutics with anxiolytic activity.

KW - lolitrem B

KW - mouse

UR - https://www.ans.org.au/images/pdf/220.pdf

UR - https://www.ans.org.au/resources/past-ans-conferences/57-past-ans-conferences

UR - http://aomevents.com/ANS2016

UR - http://aomevents.com/media/files/ANS/ANS%202016%20Program%20FINAL%20021216.pdf

M3 - Poster

SP - 109

EP - 110

ER -

Combs MA, Edwards S, Kessell AE, Hamlin A, Scherpenhuizen J, Narayan E et al. Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B. 2016. Poster session presented at 36th Annual Meeting of the Australasian Neuroscience Society, Hobart, Australia.