Drospirenone induces the accumulation of triacylglycerides in the fish hepatoma cell line, PLHC-1

Drospirenone (DRO) is one of the most commonly used progestins reaching the aquatic environment through wastewater treatment plant effluents. It is a progesterone receptor agonist, and as such, can act primarily in the brain and reproductive organs of fish. In order to better understand and predict its effects, this work evaluates the lipidomic changes induced in PLHC-1 cells after exposure to drospirenone at concentrations below the EC10 (1 and 10 mu M) by direct injection of the lipid extracts into a ESI(+/-) Orbitrap mass spectrometer. A significant accumulation of triacylglycerides, particularly long chain ones with unsaturated fatty add moieties (TG5 46:2, 56:4-7; 58:5-8) and a concomitant decrease of diacylglycerides (DGs 32:1, 34:1-2, 36:1-2, 38:2-4) was observed after 48 h exposure to 10 mu M DRO, which corresponded to an intracellular concentration of 83 ng.mg(-1) protein. No significant alteration of PLHC-1 cell lipids was observed following exposure to 1 mu M DRO. EC50 for the cytotoxicity of DRO ranged from 105 to 119 mu M (24 h exposure) to 51-58 mu M (48 h exposure). The study evidences a dysregulation of neutral lipid metabolism and increased TG/DG ratio in fish hepatic cells exposed to DRO. (C) 2019 Elsevier B.V. All rights reserved.