Peripheral neuroprotective potential and toxicological profile of fascaplysin in zebrafish models.

Abstract

Fascaplysin is a bioactive compound derived from marine sponges, which have anticancer properties and potential neuroprotective effects mediated by mitigation of oxidative stress-induced neurotoxicity. This study investigated the 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 concentrations ranging from 10 nM to 100 μM, and developmental parameters were assessed. At higher concentrations (≥1 μM), fascaplysin significantly decreased embryo survival rates, delayed hatching, impaired cardiac function, and caused morphological abnormalities, 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 of superoxide-producing enzymes and preserved peripheral nerve integrity following injury, as demonstrated by maintenance of fluorescence in transgenic zebrafish with expression of green fluorescent protein in Schwann cells. These findings suggest that fascaplysin exhibits peripheral neuroprotective effects at low concentrations, potentially through the reduction of oxidative stress and preservation of Schwann cell function. However, the toxicity observed at higher concentrations highlights the importance of dose optimization. Fascaplysin is a promising candidate for the development of new therapeutic strategies for peripheral neuropathies, and further studies are required to elucidate the underlying mechanisms and validate its efficacy in mammalian models.