Advances in the Understanding of Oxaliplatin-Induced Peripheral Neuropathy in Mice: 7-Chloro-4-(Phenylselanyl) Quinoline
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ORIGINAL ARTICLE
Advances in the Understanding of Oxaliplatin-Induced Peripheral Neuropathy in Mice: 7-Chloro-4-(Phenylselanyl) Quinoline as a Promising Therapeutic Agent Angélica S. Reis 1 & Jaini J. Paltian 1 & William B. Domingues 2 & Diogo L. R. Novo 3 & Gabriel P. Costa 4 & Diego Alves 4 & Vinicius F. Campos 2 & Marcia F. Mesko 3 & Cristiane Luchese 1 & Ethel A. Wilhelm 1 Received: 17 May 2020 / Accepted: 28 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In this study, the deposition of platinum in oxaliplatin (OXA)-exposed mice and the effects of the oxidative damage on the central nervous system were investigated. The relationship between the reactive species (RS) levels as well as the expression and activity of enzymes, such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and acetylcholinesterase (AChE), in the development of peripheral neuropathy after OXA exposure, was evidenced. The effects of 7-chloro4-(phenylselanyl) quinoline (4-PSQ) on OXA-induced peripheral neuropathy was also investigated. Swiss mice received OXA (10 mg kg−1) or vehicle by intraperitoneal route (days 0 and 2). Oral administration of 4-PSQ (1 mg kg−1) or vehicle was performed on days 2 to 14. Behavioural tasks started on day 9, after the first OXA administration. It was observed that 4-PSQ reduced the mechanical and thermal hypersensitivity induced by OXA. 4-PSQ and OXA did not affect locomotor and exploratory activities. The results revealed, for the first time, a high concentration of platinum in the spinal cord of mice exposed to OXA. 4-PSQ reversed the increased levels of RS in the spinal cord, cerebral cortex and hippocampus of mice exposed to OXA. The alterations in the activity and expression of the GPx, SOD, CAT and AChE induced by OXA exposure were normalized by 4-PSQ. Therefore, the 4-PSQ might be a good prototype for the development of a more effective drug for the treatment of OXAinduced peripheral neuropathy. The results obtained by the present study expanded the knowledge about the mechanisms involved in the physiopathology of peripheral neuropathy. Highlights • A high platinum concentration in the spinal cord of mice exposed to OXA was revealed. • Platinum deposition influenced oxidative damage on central nervous system of mice. • 4-PSQ was a promising agent to reduce the hypersensitivity OXAinduced. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02048-4) contains supplementary material, which is available to authorized users. * Cristiane Luchese [email protected] * Ethel A. Wilhelm [email protected] 1
Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica, CCQFA, Universidade Federal de Pelotas, UFPel, Pelotas, RS CEP 96010-900, Brazil
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Programa de Pós-graduação em Biotecnologia, Laboratório de Genômica Estrutural, Biotecnologia, Universidade Federal de Pelotas, UFPel, Pelotas, RS CEP 96010-900, Brazil
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Program
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