Cutaneous effects of ovatoxin-a: an in vitro study on human skin keratinocytes

Ovatoxin-a (OVTX-a) is the main palytoxin (PLTX) analogue produced by the marine benthic dinoflagellate Ostreopsis cf. ovata from the Mediterranean area, where it poses risks for human health mainly through inhalation of marine aerosols and/or skin contact with contaminated seawater. Herein, we highlight the effects of OVTX-a, in comparison to PLTX, at the skin level using human HaCaT keratinocytes, employing a sample containing OVTX-a at 86% purity. After 4 h exposure, OVTX-a reduced cell viability (EC₅₀ = 8.3 × 10^-9 M) with one order of magnitude lower potency than PLTX (EC₅₀ = 3.7 × 10^-10 M). Accordingly, OVTX-a induced lower levels of cell necrosis and mitochondrial depolarization than PLTX, but a 1-h-exposure to each toxin provoked similar increases in ROS production. Moreover, cells co-exposure to ouabain, an inhibitor of Na⁺/K⁺ ATPase, the molecular target of PLTX, or to diphenyliodonium chloride, a non-specific inhibitor of flavoprotein-based enzymes involved in PLTX-induced oxidative stress, suggested that OVTX-a and PLTX share not only the same molecular target, but also the same mechanism of ROS-dependent cytotoxicity. Overall, these results provide new evidence on OVTX-a hazard characterization at the skin level, clarifying its mechanism of action at the basis of cutaneous adverse effects experienced by bathers during O. cf. ovata blooms.