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 language | English |
|---|---|
| Article number | e0156039 |
| Journal | PLoS One |
| Volume | 11 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1 2016 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Inhibition of spinal oxidative stress by bergamot polyphenolic fraction attenuates the development of morphine induced tolerance and hyperalgesia in mice. / Lauro, Filomena; Giancotti, Luigino Antonio; Ilari, Sara; Dagostino, Concetta; Gliozzi, Micaela; Morabito, Chiara; Malafoglia, Valentina; Raffaeli, William; Muraca, Maurizio; Goffredo, Bianca M.; Mollace, Vincenzo; Muscoli, Carolina.
In: PLoS One, Vol. 11, No. 5, e0156039, 01.05.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of spinal oxidative stress by bergamot polyphenolic fraction attenuates the development of morphine induced tolerance and hyperalgesia in mice
AU - Lauro, Filomena
AU - Giancotti, Luigino Antonio
AU - Ilari, Sara
AU - Dagostino, Concetta
AU - Gliozzi, Micaela
AU - Morabito, Chiara
AU - Malafoglia, Valentina
AU - Raffaeli, William
AU - Muraca, Maurizio
AU - Goffredo, Bianca M.
AU - Mollace, Vincenzo
AU - Muscoli, Carolina
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84973333405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84973333405&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0156039
DO - 10.1371/journal.pone.0156039
M3 - Article
AN - SCOPUS:84973333405
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e0156039
ER -