Emerging Therapeutic Targets in Oxaliplatin-Induced Acute Peripheral Neuropathy: Biochemical Protection by Organoselenium via Redox and Ionic Regulation.

Oxaliplatin (OXA), a platinum-based chemotherapeutic agent, frequently induces acute peripheral neuropathy characterized by mechanical and cold allodynia, for which effective therapeutic options remain limited. Here, we investigated the acute antinociceptive and biochemical effects of 4-amino-3-(phenylselanyl)benzenesulfonamide (4-APSB), a compound with antioxidant and antinociceptive properties, in female Wistar rats with OXA-induced acute neuropathy. Animals received OXA (4 mg/kg, i.p.) on two consecutive days and were subsequently treated with 4-APSB (1 mg/kg, i.g.) or duloxetine (30 mg/kg, i.g.) as a reference drug. Nociceptive behaviors were assessed using mechanical and cold sensitivity assays, followed by biochemical analyses in nervous tissues. OXA administration induced mechanical and cold hypersensitivity, elevated oxidative stress markers, and disrupted membrane enzyme function, reducing Na+/K+-ATPase activity and increasing acetylcholinesterase (AChE) activity. Treatment with 4-APSB significantly attenuated hypersensitivity, increased Na+/K+-ATPase and catalase activities, reduced reactive species generation, and attenuated the OXA-induced increase in AChE activity in the cerebral cortex, without affecting locomotor behavior. Collectively, these findings show that 4-APSB produces acute antinociceptive effects accompanied by the modulation of redox homeostasis, Na+/K+-ATPase activity, and AChE activity following OXA exposure. The coordinated improvement in behavioral and biochemical parameters supports the potential relevance of redox balance and membrane-associated enzyme function to the pharmacological effects of 4-APSB. These results identify 4-APSB as a promising compound for further investigation as a therapeutic strategy for OXA-induced peripheral neuropathy.