title: Pharmacological effect of a new idebenone formulation in a model of carrageenan-induced inflammatory pain.
abstract: Considerable evidence demonstrated that the central role of reactive oxygen species and reactive nitrogen species (ROS and RNS) in the development of thermal hyperalgesia is associated to acute and chronic inflammation. Idebenone (IDE), a synthetic analogue of the endogenous cellular antioxidant coenzyme Q10 (CoQ10), is an active drug in the central nervous system which shows a protection in a variety of neurological disorders. Since it is lipophilic, poorly water soluble and highly bound to plasma proteins, different technological approaches have been explored to increase its solubility and new pharmaceutical properties. Therefore, it has been complexed with HP-β-cyclodextrins (HP) and its efficacy has been assessed in an animal model of carrageenan-induced thermal hyperalgesia. All male rats used for this study received a subplantar injection of carrageenan into the right hindpaw in the presence or absence of IDE alone and IDE/HP complex. We observed that IDE poorly reduced painful carrageenan effects whereas IDE/HP complex was able to prevent carrageenan-induced hyperalgesia and edema in a dose-dependent manner, reducing spinal MDA levels and protein nitration. Hence, our results demonstrated that when complexed with HP, idebenone exerts a potent analgesic and anti-inflammatory efficacy.
authors.affiliation: IRCCS San Raffaele, Roccelletta di Borgia, 88021, Catanzaro, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Lauro
authors.affiliation: IRCCS San Raffaele, Roccelletta di Borgia, 88021, Catanzaro, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ilari
authors.affiliation: IRCCS San Raffaele, Roccelletta di Borgia, 88021, Catanzaro, Italy.
authors.forename: Luigino Antonio
authors.initials: LA
authors.lastname: Giancotti
authors.affiliation: Department of Drug Science & Health Products, University of Messina, Viale Annunziata, 98168, Messina, Italy.
authors.forename: Cinzia Anna
authors.initials: CA
authors.lastname: Ventura
authors.affiliation: Department of Experimental Medicine, ⿿Sapienza⿿ University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Morabito
authors.affiliation: Institute of Research for Food Safety & Health (IRC_FSH), Department of Health Sciences, University ⿿Magna Graecia⿿ of Catanzaro, Campus ⿿Salvatore Venuta⿿ Viale Europa ⿿ Località Germaneto, 88100, Catanzaro, Italy.
authors.forename: Micaela
authors.initials: M
authors.lastname: Gliozzi
authors.affiliation: Institute for Research on Pain, ISAL-Foundation, Torre Pedrera, 47922, Rimini, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Malafoglia
authors.affiliation: Institute of Research for Food Safety & Health (IRC_FSH), Department of Health Sciences, University ⿿Magna Graecia⿿ of Catanzaro, Campus ⿿Salvatore Venuta⿿ Viale Europa ⿿ Località Germaneto, 88100, Catanzaro, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Palma
authors.affiliation: Department of Experimental and Clinical Medicine, University ⿿Magna Graecia⿿ of Catanzaro, Campus ⿿Salvatore Venuta⿿ Viale Europa ⿿ Località Germaneto, 88100, Catanzaro, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Paolino
authors.affiliation: Institute of Research for Food Safety & Health (IRC_FSH), Department of Health Sciences, University ⿿Magna Graecia⿿ of Catanzaro, Campus ⿿Salvatore Venuta⿿ Viale Europa ⿿ Località Germaneto, 88100, Catanzaro, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mollace
authors.affiliation: Institute of Research for Food Safety & Health (IRC_FSH), Department of Health Sciences, University ⿿Magna Graecia⿿ of Catanzaro, Campus ⿿Salvatore Venuta⿿ Viale Europa ⿿ Località Germaneto, 88100, Catanzaro, Italy. Electronic address: muscoli@unicz.it.
authors.forename: Carolina
authors.initials: C
authors.lastname: Muscoli
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin / Q000737:chemistry; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002351:Carrageenan; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D014451:Ubiquinone; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D008315:Malondialdehyde; D002351:Carrageenan; D013482:Superoxide Dismutase; C036619:idebenone
keywords: Antioxidant; HP-β-cyclodextrins; Idebenone; Inflammatory pain; Oxidative stress