期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 791, 期 -, 页码 51-61出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2016.08.003
关键词
Cisplatin; Edaravone; Oxido-nitrosative stress; Neurobehavioral deficits; Neuroinflammation
资金
- Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India
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 (5 mg/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, NE-kappa B activation and down regulation of Nrf2/HO-1 gene expression level in the hippocampus. Edaravone (10 mg/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 NE-kappa B 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. (C) 2016 Elsevier B.V. All rights reserved.
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