Contribution of antioxidant action of 7-chloro-4-(phenylselanyl)quinoline to treat streptozotocin-induced diabetic neuropathy in mice

Abstract

Hyperglycemia caused by diabetes mellitus contributes to complications such as diabetic neuropathy (DN), and its high prevalence and consequent economic costs make developing alternative therapies crucial. Given this scenario, this study aimed to investigate the effects of the 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) on streptozotocin (STZ)-induced DN in mice. To develop the DN, the animals received STZ (200 mg kg⁻¹, intraperitoneally, i.p.) or citrate buffer (10 ml kg⁻¹, i.p.) on day 1 of the experimental protocol. Subsequently, the blood glucose and body weight of the animals were measured. From day 21 to 35 of the experimental protocol, the mice received canola oil (10 mL kg⁻¹, intragastrically, i.g.) or 4-PSQ (5 mg kg⁻¹, i.g.) once a day. Behavioral tests were performed on days 0, 21, 24, 28, and 36 to assess the animals’ mechanical and thermal hypersensitivities. For the first time, the effects of the 4-PSQ on mechanical and thermal hypersensitivities caused by STZ were observed, and the results indicated that these pharmacological effects of 4-PSQ seem to be associated with the reduction of blood glucose levels and modulation of oxidative stress parameters, such as levels of reactive oxygen species (ROS), non-protein thiols, and the activity of antioxidant enzymes in the cerebral cortex, hippocampus, and spinal cord of mice. Furthermore, our findings showed a significant positive correlation between blood glucose levels and markers of oxidative stress, as well as a significant negative correlation between mechanical sensitivity and thermal sensitivity and markers of oxidative stress. In conclusion, 4-PSQ appears to be therapeutically beneficial for DN treatment.