Nrf2/HO-1 Pathway Mediates the Protective Impact of Metrnl on Oxaliplatin-Induced Peripheral Neuropathy in Rats

Abstract

Introduction: While oxaliplatin (OXL) is an effective cancer chemotherapy, OXL-based therapy's practical usefulness is limited by its adverse effects, which include peripheral neuropathy (PN).Objective: to assess the potential underlying processes and the protective impact of metrnl in PN caused by OXL. Materials and Methods: There were three groups of thirty adult male albino rats: control, OXL and OXL+Metrnl groups (10/group). Electromyography (EMG) and nerve conduction velocity (NCV) were applied to rats, together with behavioral testing for pain and sensory abnormalities. The expression of several genes was evaluated in the sciatic nerve, including tissue MDA, (SOD), TNF-α, interleukin (IL)-6, IL-10, caspase-3, BDNF, nuclear factor E2‐related factor 2 (Nrf2), and homo-oxygenase 1 (HO-1). Additionally, histopathological evaluations of the gastrocnemius and sciatic nerve were carried out. Results The OXL group exhibited mechanical and cold allodynia, as well as significantly higher levels of MDA, TNF-α, IL-6, and caspase-3 than the control group. It also significantly reduced NCV, EMG recordings, IL-10, as well as down-regulating BDNF, Nrf2 and HO-1 gene expression in the sciatic nerve. OXL-induced PN changes were significantly ameliorated in the OXL+Metrnl groups. Conclusion: Metrnl has valuable protective effects on OXL-induced PN via anti-oxidant, anti-inflammatory, inhibition of apoptosis and neurotrophic effects in addition to up-regulation of Nrf2 and HO-1 gene expressions.