University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Physiology
  • Physiology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Physiology
  • Physiology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Role of oxidative stress in oxaliplatin-induced enteric neuropathy and colonic dysmotility in mice

    Thumbnail
    Download
    Published version (2.467Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    33
    33
    Author
    McQuade, RM; Carbone, SE; Stojanovska, V; Rahman, A; Gwynne, RM; Robinson, AM; Goodman, CA; Bornstein, JC; Nurgali, K
    Date
    2016-12-01
    Source Title
    British Journal of Pharmacology
    Publisher
    WILEY
    University of Melbourne Author/s
    Bornstein, Joel; Gwynne, Rachel; Goodman, Craig; McQuade, Rachel
    Affiliation
    Physiology
    Medicine and Radiology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    McQuade, R. M., Carbone, S. E., Stojanovska, V., Rahman, A., Gwynne, R. M., Robinson, A. M., Goodman, C. A., Bornstein, J. C. & Nurgali, K. (2016). Role of oxidative stress in oxaliplatin-induced enteric neuropathy and colonic dysmotility in mice. BRITISH JOURNAL OF PHARMACOLOGY, 173 (24), pp.3502-3521. https://doi.org/10.1111/bph.13646.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257766
    DOI
    10.1111/bph.13646
    Abstract
    BACKGROUND AND PURPOSE: Oxaliplatin is a platinum-based chemotherapeutic drug used as a first-line therapy for colorectal cancer. However, its use is associated with severe gastrointestinal side-effects resulting in dose limitations and/or cessation of treatment. In this study, we tested whether oxidative stress, caused by chronic oxaliplatin treatment, induces enteric neuronal damage and colonic dysmotility. EXPERIMENTAL APPROACH: Oxaliplatin (3 mg·kg-1 per day) was administered in vivo to Balb/c mice intraperitoneally three times a week. The distal colon was collected at day 14 of treatment. Immunohistochemistry was performed in wholemount preparations of submucosal and myenteric ganglia. Neuromuscular transmission was studied by intracellular electrophysiology. Circular muscle tone was studied by force transducers. Colon propulsive activity studied in organ bath experiments and faeces were collected to measure water content. KEY RESULTS: Chronic in vivo oxaliplatin treatment resulted in increased formation of reactive oxygen species (O2 -), nitration of proteins, mitochondrial membrane depolarisation resulting in the release of cytochrome c, loss of neurons, increased inducible NOS expression and apoptosis in both the submucosal and myenteric plexuses of the colon. Oxaliplatin treatment enhanced NO-mediated inhibitory junction potentials and altered the response of circular muscles to the NO donor, sodium nitroprusside. It also reduced the frequency of colonic migrating motor complexes and decreased circular muscle tone, effects reversed by the NO synthase inhibitor, Nω-Nitro-L-arginine. CONCLUSION AND IMPLICATIONS: Our study is the first to provide evidence that oxidative stress is a key player in enteric neuropathy and colonic dysmotility leading to symptoms of chronic constipation observed in oxaliplatin-treated mice.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [53039]
    • Medicine and Radiology - Research Publications [3320]
    • Physiology - Research Publications [390]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors