Omega-3-Enriched Fish oil reduces the chemotherapy-induced peripheral neuropathy in mice

Cancer is a leading cause of mortality and morbidity worldwide and conventional chemotherapy frequently induce irreversible adverse effects in patients. Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of both paclitaxel (PTX) and oxaliplatin (OXA) chemotherapies, affecting approximately 30-50% of patients. As cancer survival rates have improved, the efforts of scientific community to develop new strategies for preventing CIPN are also growing. This study presents the effects of omega-3 (ω-3)-enriched fish oil supplementation on the hypersensitivity induced by PTX or OXA in mice. GC-MS analysis of the fish oil revealed an amount of EPA and DHA corresponding to 55.2% and 37.4% of total oil composition, respectively. The thirty-day supplementation with the fish oil prevented the cold hypersensitivity induced by the acute OXA injection protocol, with reduction of spinal cord microglia activation, as well as decreased levels of cytokines and BDNF in the spinal cord and brain. A similar effect was observed with the chronic OXA administration, reducing both mechanical and thermal hypersensitivity. The fish oil also prevented PTX-induced neuropathy, accompanied by a reduction in cytokine levels. It is important to mention that biochemical parameters such as total cholesterol, triglycerides and glucose were also normalised. The fish oil supplementation prevented the development of hypersensitivity in both OXA and PTX models, with reduced neuroinflammation likely being the main mechanism behind this effect. The fish oil supplementation, either before or during chemotherapy, could be an important ally to prevent and treat CIPN, improving the patients' quality of life post-cancer treatment.