Interface of Aging and Acute Peripheral Neuropathy Induced by Oxaliplatin in Mice: Target-Directed Approaches for Na+, K+-ATPase, Oxidative Stress, and 7-Chloro-4-(phenylselanyl) quinoline Therapy

Almost 90% of patients develop pain immediately after oxaliplatin (OXA) treatment. Here, the impact of aging on OXA-induced acute peripheral neuropathy and the potential of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) as a new therapeutic strategy were evaluated. In Swiss mice, the oxidative damage and its influence on Mg2+-ATPase and Na+, K+-ATPase activities were investigated. The relationship between the reactive oxygen species (ROS) and nitrate and nitrite (NOx) levels, the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD) with the development of OXA-induced acute peripheral neuropathy was also studied. In this study, it was evidenced that OXA-induced acute peripheral neuropathy was exacerbated by aging through increased oxidative damage as well as Na+, K+-ATPase, and Mg+2-ATPase inhibition. 4-PSQ reversed hypersensitivity induced by OXA and aging-aggravated by reducing ROS and NOx levels, through modulation of GPx and SOD activities. 4-PSQ partially reestablish Na+, K+-ATPase activity, but not Mg2+-ATPase activity. Locomotor and exploratory activities were not affected. This study is the first of its kind, providing new insight into the aging impact on mechanisms involved in OXA-induced acute peripheral neuropathy. Also, it provides evidence on promising 4-PSQ effects on this condition, mainly on aging.

Automated summary

This study evaluates the impact of aging on oxaliplatin-induced acute peripheral neuropathy and explores the potential of 7-chloro-4-(phenylselanyl) quinoline as a new therapeutic strategy. The results show that aging exacerbates the pain caused by oxaliplatin through increased oxidative damage and inhibition of Na+, K+-ATPase and Mg2+-ATPase. However, 4-PSQ can reverse the hypersensitivity induced by oxaliplatin and aging by reducing ROS and NOx levels and modulating GPx and SOD activities.