S-106 | Resveratrol Prevents Chemotherapy-Induced Neuropathy Without Compromising Antitumor Activity: Insights from an Oxaliplatin-Induced Neuropathy Model

Neural excitability, synaptic transmission and neuron-glia interactions
Author: CONSTANZA MIGUEL | Email: constanzaagata@gmail.com

Constanza Miguel^1°, Tobias Giovannetti^1°, Mariel Fusco^1°,  Flavia Piccioni^1°, Mariana Malvicini^1°, Florencia Coronel^1°

^1° Instituto de Investigaciones en Medicina Traslacional, CONICET – Universidad Austral

Oxaliplatin (OXA), a first-line chemotherapeutic agent, exerts peripheral neurotoxic damage leading to sensory, motor, and autonomic symptoms. No current strategies effectively prevent or reverse chemotherapy-induced peripheral neuropathy (CIPN). This study aimed to assess sensory and motor impairments, as well as the underlying mechanisms. We also evaluated resveratrol’s effectiveness in preventing CIPN. Adult rats received OXA or saline. Resveratrol was administered daily before the chemotherapy regimen (preventive strategy, RESVp). Mechanical and thermal allodynia and locomotor function were assessed. To confirm resveratrol’s non-interference with OXA’s antitumor effects, adult Balb C mice were injected with CT26 cells and treated with OXA and RESVp. OXA-treated rats developed mechanical and thermal hypersensitivity and allodynia. No impairments in locomotor function were detected. OXA-treated animals showed increased ATF-3, GFAP, IBA-1, NFκB, TNF-α and HMGB1 expression levels in dorsal root ganglia. RESV administration prevented allodynia and did not interfere with OXA’s antitumor actions. RESVp increased GSH stores and SIRT-1, NRF-2 and NQO-1 mRNA levels, and decreased TBARS levels and ATF-3, NF-κB and TNF-α expression. Thus, early and sustained RESV administration effectively prevented OXA-induced pain without interfering with its antitumor activity. RESVp increased antioxidant reserves, reduced oxidative damage and mitigated neuroinflammation and neuronal damage.