Acute paraquat exposure impairs colonic motility by selectively attenuating nitrergic signaling in the mouse

Lucy Diss, Sarah Dyball, Tina Ghela, Jonathan Golding, Rachel Morris, Stephen Robinson, Rosemary Tucker, Talia Walter, Paul Young, Marcus Allen, Sara Fidalgo, Paul Gard, Jon Mabley, Bhavik Patel, Prabal Chatterjee, Mark Yeoman

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Paraquat, a common herbicide, is responsible for large numbers of deaths worldwide through both deliberate and accidental ingestion. Previous studies have eluded that the bioavailability of paraquat increases substantially with increasing dose and that these changes may in part be due to the effects these high concentrations have on the gastrointestinal tract (GI tract). To date, the actions of acute, high concentrations (20 mM for 60 minutes) of paraquat on the GI tract, particularly the colon a major site of paraquat absorption, are unknown. This study examined the effects of acute paraquat administration on colonic motility in the C57BL/6 mouse. Acute paraquat exposure decreased colonic motility and the amplitude of colonic migrating motor complexes (CMMCs), major motor patterns involved in faecal pellet propulsion. In isolated segments of distal colon, paraquat increased resting tension and markedly attenuated electrical field stimulation-evoked relaxations. Pharmacological dissection of paraquat’s mechanism of action on both the CMMCs and field stimulated tissue using the nitric oxide synthase inhibitor NG-nitro-L-Arginine and direct measurement of NO release from the myenteric plexus, demonstrated that paraquat selectively attenuates nitrergic signaling pathways. These changes did not appear to be due to alterations in colonic oxidative stress, inflammation or complex 1 activity, but were most likely caused by paraquat’s ability to act as a redox couple. In summary, these data demonstrate that acute paraquat exposure attenuates colonic transit. These changes may facilitate the absorption of paraquat into the circulation and so facilitate its toxicity.
Original languageEnglish
Pages (from-to)8-15
Number of pages8
JournalAutonomic Neuroscience-Basic & Clinical
Volume195
DOIs
Publication statusPublished - 30 Jan 2016

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Paraquat
Migrating Myoelectric Complexes
Gastrointestinal Tract
Colon
Myenteric Plexus
Nitroarginine
Herbicides
Inbred C57BL Mouse
Nitric Oxide Synthase
Electric Stimulation
Biological Availability
Oxidation-Reduction
Dissection
Oxidative Stress
Eating
Pharmacology
Inflammation

Bibliographical note

© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Cite this

Diss, Lucy ; Dyball, Sarah ; Ghela, Tina ; Golding, Jonathan ; Morris, Rachel ; Robinson, Stephen ; Tucker, Rosemary ; Walter, Talia ; Young, Paul ; Allen, Marcus ; Fidalgo, Sara ; Gard, Paul ; Mabley, Jon ; Patel, Bhavik ; Chatterjee, Prabal ; Yeoman, Mark. / Acute paraquat exposure impairs colonic motility by selectively attenuating nitrergic signaling in the mouse. In: Autonomic Neuroscience-Basic & Clinical. 2016 ; Vol. 195. pp. 8-15.
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abstract = "Paraquat, a common herbicide, is responsible for large numbers of deaths worldwide through both deliberate and accidental ingestion. Previous studies have eluded that the bioavailability of paraquat increases substantially with increasing dose and that these changes may in part be due to the effects these high concentrations have on the gastrointestinal tract (GI tract). To date, the actions of acute, high concentrations (20 mM for 60 minutes) of paraquat on the GI tract, particularly the colon a major site of paraquat absorption, are unknown. This study examined the effects of acute paraquat administration on colonic motility in the C57BL/6 mouse. Acute paraquat exposure decreased colonic motility and the amplitude of colonic migrating motor complexes (CMMCs), major motor patterns involved in faecal pellet propulsion. In isolated segments of distal colon, paraquat increased resting tension and markedly attenuated electrical field stimulation-evoked relaxations. Pharmacological dissection of paraquat’s mechanism of action on both the CMMCs and field stimulated tissue using the nitric oxide synthase inhibitor NG-nitro-L-Arginine and direct measurement of NO release from the myenteric plexus, demonstrated that paraquat selectively attenuates nitrergic signaling pathways. These changes did not appear to be due to alterations in colonic oxidative stress, inflammation or complex 1 activity, but were most likely caused by paraquat’s ability to act as a redox couple. In summary, these data demonstrate that acute paraquat exposure attenuates colonic transit. These changes may facilitate the absorption of paraquat into the circulation and so facilitate its toxicity.",
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Acute paraquat exposure impairs colonic motility by selectively attenuating nitrergic signaling in the mouse. / Diss, Lucy; Dyball, Sarah; Ghela, Tina; Golding, Jonathan; Morris, Rachel; Robinson, Stephen; Tucker, Rosemary; Walter, Talia; Young, Paul; Allen, Marcus; Fidalgo, Sara; Gard, Paul; Mabley, Jon; Patel, Bhavik; Chatterjee, Prabal; Yeoman, Mark.

In: Autonomic Neuroscience-Basic & Clinical, Vol. 195, 30.01.2016, p. 8-15.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Diss, Lucy

AU - Dyball, Sarah

AU - Ghela, Tina

AU - Golding, Jonathan

AU - Morris, Rachel

AU - Robinson, Stephen

AU - Tucker, Rosemary

AU - Walter, Talia

AU - Young, Paul

AU - Allen, Marcus

AU - Fidalgo, Sara

AU - Gard, Paul

AU - Mabley, Jon

AU - Patel, Bhavik

AU - Chatterjee, Prabal

AU - Yeoman, Mark

N1 - © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

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Y1 - 2016/1/30

N2 - Paraquat, a common herbicide, is responsible for large numbers of deaths worldwide through both deliberate and accidental ingestion. Previous studies have eluded that the bioavailability of paraquat increases substantially with increasing dose and that these changes may in part be due to the effects these high concentrations have on the gastrointestinal tract (GI tract). To date, the actions of acute, high concentrations (20 mM for 60 minutes) of paraquat on the GI tract, particularly the colon a major site of paraquat absorption, are unknown. This study examined the effects of acute paraquat administration on colonic motility in the C57BL/6 mouse. Acute paraquat exposure decreased colonic motility and the amplitude of colonic migrating motor complexes (CMMCs), major motor patterns involved in faecal pellet propulsion. In isolated segments of distal colon, paraquat increased resting tension and markedly attenuated electrical field stimulation-evoked relaxations. Pharmacological dissection of paraquat’s mechanism of action on both the CMMCs and field stimulated tissue using the nitric oxide synthase inhibitor NG-nitro-L-Arginine and direct measurement of NO release from the myenteric plexus, demonstrated that paraquat selectively attenuates nitrergic signaling pathways. These changes did not appear to be due to alterations in colonic oxidative stress, inflammation or complex 1 activity, but were most likely caused by paraquat’s ability to act as a redox couple. In summary, these data demonstrate that acute paraquat exposure attenuates colonic transit. These changes may facilitate the absorption of paraquat into the circulation and so facilitate its toxicity.

AB - Paraquat, a common herbicide, is responsible for large numbers of deaths worldwide through both deliberate and accidental ingestion. Previous studies have eluded that the bioavailability of paraquat increases substantially with increasing dose and that these changes may in part be due to the effects these high concentrations have on the gastrointestinal tract (GI tract). To date, the actions of acute, high concentrations (20 mM for 60 minutes) of paraquat on the GI tract, particularly the colon a major site of paraquat absorption, are unknown. This study examined the effects of acute paraquat administration on colonic motility in the C57BL/6 mouse. Acute paraquat exposure decreased colonic motility and the amplitude of colonic migrating motor complexes (CMMCs), major motor patterns involved in faecal pellet propulsion. In isolated segments of distal colon, paraquat increased resting tension and markedly attenuated electrical field stimulation-evoked relaxations. Pharmacological dissection of paraquat’s mechanism of action on both the CMMCs and field stimulated tissue using the nitric oxide synthase inhibitor NG-nitro-L-Arginine and direct measurement of NO release from the myenteric plexus, demonstrated that paraquat selectively attenuates nitrergic signaling pathways. These changes did not appear to be due to alterations in colonic oxidative stress, inflammation or complex 1 activity, but were most likely caused by paraquat’s ability to act as a redox couple. In summary, these data demonstrate that acute paraquat exposure attenuates colonic transit. These changes may facilitate the absorption of paraquat into the circulation and so facilitate its toxicity.

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