Inhibition of spinal oxidative stress by bergamot polyphenolic fraction attenuates the development of morphine induced tolerance and hyperalgesia in mice

Filomena Lauro, Luigino Antonio Giancotti, Sara Ilari, Concetta Dagostino, M. Gliozzi, Chiara Morabito, Valentina Malafoglia, William Raffaeli, Maurizio Muraca, Bianca Maria Goffredo, Vincenzo Mollace, Carolina Muscoli

Research output: Contribution to journalArticle

Abstract

Citrus Bergamia Risso, commonly known as Bergamot, is a fruit whose Essential Oil and Bergamot Polyphenolic Fraction have numerous medicinal properties. It is also an excellent antioxidant and in this study, for the first time, its potential effect on morphine induced tolerance in mice has been investigated. Our studies revealed that development of antinociceptive tolerance to repeated doses of morphine in mice is consistently associated with increased formation of superoxide, malondialdehyde and tyrosine-nitrated proteins in the dorsal horn of the spinal cord such as the enzyme glutamine synthase. Nitration of this protein is intimately linked to inactivation of its biological function and resulting increase of glutamate levels in the spinal cord. Administration of Bergamot Polyphenolic Fraction (5-50 mg/kg) attenuated tolerance development. This effect was accompanied by reduction of superoxide and malondialdehyde production, prevention of GS nitration, re-establishment of its activity and of glutamate levels. Our studies confirmed the main role of free radicals during the cascade of events induced by prolonged morphine treatment and the co-administration of natural derivatives antioxidant such as Bergamot Polyphenolic Fraction can be an important therapeutic approach to restore opioids analgesic efficacy.

Original languageEnglish
Article numbere0156039
JournalPLoS One
Volume11
Issue number5
DOIs
Publication statusPublished - May 1 2016

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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