Advances in the Understanding of Oxaliplatin-Induced Peripheral Neuropathy in Mice: 7-Chloro-4-(Phenylselanyl) Quinoline as a Promising Therapeutic Agent.

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-chloro-4-(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 OXA-induced peripheral neuropathy. The results obtained by the present study expanded the knowledge about the mechanisms involved in the physiopathology of peripheral neuropathy. Graphical abstract.