title: Poly (ADP-ribose) polymerase-1 inhibitor, 3-aminobenzamide pretreatment ameliorates lipopolysaccharide-induced neurobehavioral and neurochemical anomalies in mice.
abstract: Poly (ADP-ribose) polymerase-1 (PARP-1) functions at the center of cellular stress and sways the immune system at several key points, thus modulates inflammatory diseases. The antiinflammatory properties of PARP-1 inhibitors have been demonstrated ameliorating effect in various neuroinflammatory disorders. It has been reported that there is a close relationship between the inflammatory processes and major depressive disorder. In the present study, we have elucidated the role of oxidative-nitrosative stress-PARP-1 pathway in lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical alterations in mice. 3-Aminobenzamide (10 and 30mg/kg) and imipramine (10 and 30mg/kg) were administered once daily for 14days. Mice were challenged with LPS (1mg/kg, i.p.) 30min after drug administration on the 14th day. The mRNA expression level of PARP-1 (12h after LPS injection) in the hippocampus was measured through quantitative real-time PCR. All the behavioral and biochemical parameters were assessed at 24h after LPS injection. The expression level of PARP-1mRNA was found significantly up-regulated in the hippocampus at 12h after LPS administration. Results showed that the LPS-challenged mice exhibited an increase in immobility time seen in forced swimming test and tail suspension test. LPS increased the levels of proinflammatory cytokines and oxido-nitrosative stress parameters in the hippocampus. However, pretreatment with 3-aminobenzamide (30mg/kg) significantly reversed the LPS-induced alterations in behavioral parameters, proinflammatory cytokines, oxidative-nitrosative stress and PARP-1 mRNA levels. Imipramine failed to prevent the up-regulation of PARP-1 induced by LPS administration. Our results emphasized that oxidative-nitrosative stress-PARP-1 cascade can play a key role in LPS-induced neurobehavioral and neurochemical anomalies.
authors: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India. Electronic address: srshekhar@yahoo.com.
authors: Chandra Shaker
authors: CS
authors: Sriram
authors: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India.
authors: Ashok
authors: A
authors: Jangra
authors: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors: Satendra Singh
authors: SS
authors: Gurjar
authors: State Biotech Hub, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India.
authors: Md Iftikar
authors: MI
authors: Hussain
authors: State Biotech Hub, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India.
authors: Probodh
authors: P
authors: Borah
authors: 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.
authors: Mangala
authors: M
authors: Lahkar
authors: Department of Pharmacology & Toxicology, College Of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India.
authors: Pritam
authors: P
authors: Mohan
authors: 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: Babul Kumar
authors: BK
authors: Bezbaruah
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001549:Benzamides; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009573:Nitrites; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009243:NAD; C025160:3-aminobenzamide; D002374:Catalase; D013482:Superoxide Dismutase; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D005978:Glutathione; D007099:Imipramine
keywords: 3-Aminobenzamide; Depressive-like behavior; Imipramine; Lipopolysaccharide; Poly (ADP-ribose) polymerase-1