Neuroprotective potential of spinochromes in a mouse model of olfactory nerve degeneration

Methimazole (MMZ) is an antithyroid drug with olfactotoxicity as an adverse effect. MMZ-induced olfatotoxicity is mediated by the generation of reactive species following MMZ metabolism in the olfactory epithelium (OE). MMZ rapidly damages sustentacular cells and Bowman’s glands, leading to OE disorganization and detachment, inflammation and neuronal dysfunction and loss, features also observed in OE damage induced by viral infection. Here, we propose to test whether a formulation of Echinochrome A (EchA), a naturally occurring spinochrome present in the roe of the Patagonian sea urchin Arbacia Dufresnii, confers neuroprotection against MMZ-induced olfactory degeneration. EchA is an antioxidant with an anti-inflammatory effect in the airways of a mouse model of asthma. We will evaluate measures of OE and nerve integrity, neuronal survival and myeloid cell infiltration and reactivity in mice treated with MMZ (25 mg/kg, intraperitoneally) or vehicle (saline solution). In this study, EchA will be administered orally as part of a roe-derived formulation with a known and standardized EchA concentration, currently used to produce an approved and commercialized dietary supplement for human consumption. Mice will receive EchA (10 mg/kg, orally, once daily) starting 7 days before MMZ administration and continuing until evaluation 3 days after the lesion, or vehicle (saline solution). We expect to determine the potential of EchA as a neuroprotectective agent against olfactory damage.