The potential amelioration of oxaliplatin-induced peripheral neuropathy in Sprague Dawley rats by sodium butyrate via targeting neuro-immuno-inflammatory axis.

Oxaliplatin is widely used as one of the first-line treatments for colorectal carcinoma. Oxaliplatin-induced peripheral neuropathy (OIPN) is the most common dose-limiting adverse effect leading to discontinuation of treatment. This work aimed to investigate the potential ameliorative effect of sodium Butyrate (NaB) on OIPN via assessment of neurotrophic factors and the immune-inflammatory axis, either before induction (PRE) or WITH the induction of OIPN in Sprague Dawley rats. In this study, OIPN was induced by oxaliplatin in a dose of 2.4 mg/kg once daily for 5 consecutive days/ week for 3 weeks by i.p. injection. Behavioral tests were performed, and the sciatic nerves were dissected and processed for further assessment of biochemical parameters and the histopathological picture. NaB has a marked neurotrophic, anti-inflammatory and immunomodulatory effect represented by a significant decrease in mechanical and cold allodynia scores and tissue levels of TNF-α and a significant increase in tissue levels of nerve growth factor (NGF) and IL-10 with a significant improvement in the histopathological changes by H&E and Toluidine blue as well as a significant increase in the IHC expression of FOXP-3 and PPAR-γ. NaB-PRE OIPN showed more improvement in the neurotrophic, anti-inflammatory, and immunomodulatory properties than NaB WITH OIPN. These elaborated data indicated that NaB is a potential neuroprotective candidate for OIPN treatment due to its immunomodulatory, anti-inflammatory, and neurotrophic effects, particularly when used before the initiation of chemotherapeutic cycles to improve the clinical aspects of OIPN.