Aging as a critical factor in chronic oxaliplatin-induced neuropathy: Protective effects of 7-chloro-4-(phenylselanyl) quinoline through modulation of NF-κB and Drp1 expression, and platinum distribution

The primary objective of the present study was to elucidate the role of dynamin-related protein 1 (Drp1) and its relationship to platinum distribution, focusing on age-related chronic OXA-induced neuropathy in rats, and to suggest 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) as a potential therapeutic strategy. Young and old Wistar rats received OXA (2 mg kg⁻¹) intraperitoneally for five days. The effects of 4-PSQ and aging on OXA-induced peripheral neuropathy, with a focus on Drp1 and platinum deposition, were investigated. Behavioral tests assessed neuropathic symptoms, while platinum concentration in different tissues, neuroinflammation, apoptotic pathways, and oxidative damage were also evaluated. This research offers insights into the mechanisms of OXA toxicity, revealing a direct correlation between platinum levels in the peripheral and central nervous systems. It highlighted how peripheral accumulation impacts central neurotoxicity and identifies aging as a factor in exacerbating chronic OXA-induced neuropathy. Our study demonstrates the potential of 4-PSQ in alleviating neuropathic symptoms by reducing nuclear factor kappa B (NF-κB) and Drp1 expression levels, mitigating oxidative stress, neuroinflammation, and related apoptotic pathways in aged rats. By elucidating the role of Drp1 and the impact of platinum distribution in the nervous system, this study highlights mechanisms underlying OXA toxicity. Reducing NF-κB and Drp1 levels by 4-PSQ suggests a pathway for alleviating oxidative stress and neuroinflammation. These results support the potential of 4-PSQ in protecting against age-related neurotoxic effects of platinum-based chemotherapy.