Peripheral neuroprotective potential and toxicological profile of fascaplysin in zebrafish models

Fascaplysin is a bioactive compound derived from marine sponges, which have anticancer properties andpotential neuroprotective effects mediated by mitigation of oxidative stress-induced neurotoxicity. This study investigatedthe concentration-dependent effects of fascaplysin in zebrafish models, focusing on embryonic survival, cardiac function,melanocyte formation, and peripheral nerve health. Zebrafish embryos were exposed to fascaplysin at concentrationsranging from 10 nM to 100 μM, and developmental parameters were assessed. At higher concentrations (≥1 μM), fascaplysinsignificantly decreased embryo survival rates, delayed hatching, impaired cardiac function, and caused morphologicalabnormalities, including disruption of melanocyte formation and structural deformities. By contrast, lower concentrations(10 nM and 100 nM) did not exhibit significant toxicity. In adult zebrafish, fascaplysin at 100 nM reduced the expression ofsuperoxide-producing enzymes and preserved peripheral nerve integrity following injury, as demonstrated by maintenanceof fluorescence in transgenic zebrafish with expression of green fluorescent protein in Schwann cells. These findings suggestthat fascaplysin exhibits peripheral neuroprotective effects at low concentrations, potentially through the reduction ofoxidative stress and preservation of Schwann cell function. However, the toxicity observed at higher concentrations highlightsthe importance of dose optimization. Fascaplysin is a promising candidate for the development of new therapeutic strategiesfor peripheral neuropathies, and further studies are required to elucidate the underlying mechanisms and validate its efficacyin mammalian models.