title: Edaravone abrogates LPS-induced behavioral anomalies, neuroinflammation and PARP-1.
abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick-sensor enzyme that functions at the center of cellular stress response and affects the immune system at several key points, and thus modulates inflammatory diseases. Our previous study demonstrated that lipopolysaccharide (LPS)-induced depressive-like behavior in mice can be ameliorated by 3-aminobenzamide, which is a PARP-1 inhibitor. In the present study we've examined the effect of a free radical scavenger, edaravone pretreatment against LPS-induced anxiety and depressive-like behavior as well as various hippocampal biochemical parameters including PARP-1. Male Swiss albino mice were treated with edaravone (3 & 10mg/kgi.p.) once daily for 14days. On the 14th day 30min after edaravone treatment mice were challenged with LPS (1mg/kgi.p.). After 3h and 24h of LPS administration we've tested mice for anxiety and depressive-like behaviors respectively. Western blotting analysis of PARP-1 in hippocampus was carried out after 12h of LPS administration. Moreover, after 24h of LPS administration serum corticosterone, hippocampal BDNF, oxido-nitrosative stress and pro-inflammatory cytokines were estimated by ELISA. Results showed that pretreatment of edaravone (10mg/kg) ameliorates LPS-induced anxiety and depressive-like behavior. Western blotting analysis showed that LPS-induced anomalous expression of PARP-1 significantly reverses by the pretreatment of edaravone (10mg/kg). Biochemical analyses revealed that LPS significantly diminishes BDNF, increases pro-inflammatory cytokines and oxido-nitrosative stress in the hippocampus. However, pretreatment with edaravone (10mg/kg) prominently reversed all these biochemical alterations. Our study emphasized that edaravone pretreatment prevents LPS-induced anxiety and depressive-like behavior, mainly by impeding the inflammation, oxido-nitrosative stress and PARP-1 overexpression.
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Chandra Shaker
authors.initials: CS
authors.lastname: Sriram
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jangra
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Satendra Singh
authors.initials: SS
authors.lastname: Gurjar
authors.affiliation: Department of Pharmacology & Toxicology, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India.
authors.forename: Pritam
authors.initials: P
authors.lastname: Mohan
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India; Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India. Electronic address: bez_bikki@yahoo.co.in.
authors.forename: Babul Kumar
authors.initials: BK
authors.lastname: Bezbaruah
mesh_terms: D000221:Adaptation, Ocular / Q000187:drug effects; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy*; D005106:Exploratory Behavior / Q000187:drug effects; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D019417:Hindlimb Suspension; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D001523:Mental Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013550:Swimming / Q000523:psychology
chemical_list: D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D002374:Catalase; D013482:Superoxide Dismutase; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D005978:Glutathione; D000077553:Edaravone; D000983:Antipyrine
keywords: Anxiety; Depressive-like behavior; Edaravone; Lipopolysaccharide; Poly(ADP-ribose) polymerase-1