NEUROPROTECTIVE EFFECT OF FLUOCINOLONE ACETONIDE ON MITOCHONDRIA IN PACLITAXEL-INDUCED PERIPHERAL NEUROPATHY

Abstract

One side effect of paclitaxel treatment, an established chemotherapy drug, is neurotoxicity, which may lead to Paclitaxel-Induced Peripheral Neuropathy (PIPN). Paraesthesia, tingling and numbness from PIPN may result in dose reduction or premature termination of the life-saving chemotherapy. Nerves with long axons are more sensitive to paclitaxel toxicity and this can be attributed to the fact that long axons are more susceptible to the dysregulation of mitochondrial dynamics. A novel mitochondrial dual-labelling method was devised, utilising the unique advantage of a compartmentalised neuron culture system. Fluocinolone Acetonide (FA), a hydrocortisone derivative, induced significant anterograde trafficking of proximal mitochondria (PM) into distal axons as a neuroprotective mechanism against PIPN. This phenomenon mitigates the damage to the distal mitochondria (DM) population and protects the axons from neurodegeneration. FA treatment recovered the paclitaxel-induced neurotoxic changes in mitochondria dynamics suggesting that its neuroprotective mechanism involved the drug-induced engagement and rescue of the mitochondria network.