title: Effects of WR1065 on 6-hydroxydopamine-induced motor imbalance: Possible involvement of oxidative stress and inflammatory cytokines.
abstract: Over production of reactive oxygen species (ROS) is postulated to be the main contributor in degeneration of nigrostriatal dopaminergic neurons. In this study we investigated the effects of WR1065, a free radical scavenger, on motor imbalance, oxidative stress parameters and inflammatory cytokines in CSF and brain of hemi-parkinsonian rats. Lesion of dopaminergic neurons was done by unilateral infusion of 6-hydroxydopamine into the central region of the substentia nigra pars compacta (SNc) to induce hemi-parkinsonism and motor imbalance in rats. WR1065 (20, 40 and 80μg/2μl/rat) was administered three days before 6-OHDA administration. After three weeks behavioral study was performed and then brain and CSF samples were collected to assess tumor necrosis factor (TNFα), interlukin (IL-1β), reduced glutathione (GSH), and malondialdehyde (MDA). WR1065 pre-treatment in rats before receiving 6-OHDA, improved significantly motor impairment and caused reduction of MDA and inflammatory cytokines TNFα and IL-1β levels, while GSH level significantly increased when compared with lesioned rats. Our study indicated that WR1065 could improve 6-OHDA-induced motor imbalance. Furthermore, it decreased lipid peroxidation and inflammatory cytokines and restored the level of GSH up to normal range. We suggest that WR1065 can be proposed as a potential neuroprotective agent in motor impairments of PD. However to prove this hypothesis more clinical trial studies should be done.
authors.affiliation: Drug Applied Research Center, Department of Pharmacology and Toxicology, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Kheradmand
authors.affiliation: Drug Applied Research Center, Department of Pharmacology and Toxicology, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: nayebia@tbzmed.ac.ir.
authors.forename: Alireza M
authors.initials: AM
authors.lastname: Nayebi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Jorjani
authors.affiliation: Medical Genomics Research Center and School of Advanced Science in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Khalifeh
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hamadan University of Medical Science, Hamadan, Iran.
authors.forename: Rasool
authors.initials: R
authors.lastname: Haddadi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005978:Glutathione / Q000134:cerebrospinal fluid; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000134:cerebrospinal fluid; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000134:cerebrospinal fluid; D008624:Mercaptoethylamines / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D065842:Pars Compacta / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
chemical_list: D053583:Interleukin-1beta; D008624:Mercaptoethylamines; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D008315:Malondialdehyde; D016627:Oxidopamine; D005978:Glutathione
keywords: 6-OHDA; GSH; IL-1β; MDA; Motor imbalance; TNFα; WR-1065