title: Edaravone alleviates cisplatin-induced neurobehavioral deficits via modulation of oxidative stress and inflammatory mediators in the rat hippocampus.
abstract: Cisplatin is a chemotherapeutic agent used in the treatment of malignant tumors. A major clinical limitation of cisplatin is its potential toxic effects, including neurotoxicity. Edaravone, a potent free radical scavenger, has been reported to have the neuroprotective effect against neurological deficits. The aim of the present study was to determine the neuroprotective effect of edaravone against cisplatin-induced behavioral and biochemical anomalies in male Wistar rats. Our results showed that cisplatin (5mg/kg/week, i.p.) administration for seven weeks caused marked cognitive deficits and motor incoordination in rats. This was accompanied by oxido-nitrosative stress, neuroinflammation, NF-κB activation and down-regulation of Nrf2/HO-1 gene expression level in the hippocampus. Edaravone (10mg/kg/week, i.p.) treatment for seven weeks inhibited the aforementioned neurobehavioral and neurochemical deficits. Furthermore, edaravone was found to up-regulate the gene expression level of Nrf2/HO-1 and prevented the cisplatin-induced NF-κB activation. These findings demonstrated that oxido-nitrosative stress and inflammatory signaling mediators play a key role in the development of cisplatin-induced neurobehavioral deficits which were prevented by edaravone treatment.
authors: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, India.
authors: Ashok
authors: A
authors: Jangra
authors: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, India.
authors: Mohit
authors: M
authors: Kwatra
authors: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, India.
authors: Tavleen
authors: T
authors: Singh
authors: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, India.
authors: Rajat
authors: R
authors: Pant
authors: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, India.
authors: Pawan
authors: P
authors: Kushwah
authors: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, India.
authors: Sahabuddin
authors: S
authors: Ahmed
authors: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, India.
authors: Durgesh
authors: D
authors: Dwivedi
authors: Department of Biotechnology, University Institute of Engineering & Technology (UIET), Maharshi Dayanand University, Rohtak, Haryana, India.
authors: Babita
authors: B
authors: Saroha
authors: Department of Pharmacology, Gauhati Medical College, Guwahati, India. Electronic address: dr.mlahkar@gmail.com.
authors: Mangala
authors: M
authors: Lahkar
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D003071:Cognition / Q000187:drug effects; D000077553:Edaravone; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D014409:Tumor Necrosis Factor-alpha; D051547:Heme Oxygenase-1; D000110:Acetylcholinesterase; D002945:Cisplatin; D000077553:Edaravone; D000983:Antipyrine
keywords: Cisplatin; Edaravone; Neurobehavioral deficits; Neuroinflammation; Oxido-nitrosative stress