title: 4-hydroxy tempo improves mitochondrial and neurobehavioral deficits in experimental model of Huntington's disease.
abstract: Mitochondrial dysfunctions have been implicated in the progression of Huntington's disease (HD). To date, several free radical scavengers have been tested in experimental HD, but only a few have shown promise. Although most antioxidants rapidly reduce ROS but in the process they are oxidized, which limits their ability to protect. Therefore, in the present study we employed a potent recycling antioxidant, 4-hydroxy tempo (4-HT), because it can reinstate its reduced state even after its oxidation during scavenging of ROS. Female Wistar rats were administered 3-nitropropionic acid (3-NP) and/or 4-HT for 21 days, after which animals were subjected to biochemical and behavioral assessments. Our results showed that 4-HT treatment significantly attenuated the 3-NP induced decrease in the activities of mitochondrial electron transport chain enzymes. In addition, 4-HT administration restored the increased nitrite and lipid peroxidation levels. Apart from this, 4-HT also attenuated the 3-NP induced decrease in superoxide dismutase and catalase activities. Further, 4-HT administration resulted in significant improvement in 3-NP induced cognitive and motor impairments. Taken together, the results of the study demonstrate that 4-HT is beneficial in 3-NP induced model of HD and thus could be a potential therapeutic agent in management of this disease.
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh, 160014, Punjab, India.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
authors.forename: Namita
authors.initials: N
authors.lastname: Mahajan
authors.forename: Arpit
authors.initials: A
authors.lastname: Mehrotra
authors.forename: Aanchal
authors.initials: A
authors.lastname: Aggarwal
authors.forename: Aditya
authors.initials: A
authors.lastname: Sunkaria
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D003071:Cognition; D003497:Cyclic N-Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D006816:Huntington Disease / Q000188:drug therapy*; D019811:Hydroxylamine / Q000494:pharmacology* / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009068:Movement; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D019811:Hydroxylamine; D002374:Catalase; D013482:Superoxide Dismutase; C505333:TEMPOL-H
keywords: 3-nitropropionic acid; 4-hydroxy tempo; Huntington's disease; mitochondria; neurobehavior; oxidative stress