Microalgae are rich in bioactive compounds including pigments, proteins, lipids, polyunsaturated fatty acids, carbohydrates, and vitamins. Due to their non-toxic and nutritious characteristics, these are suggested as important food for many aquatic animals. Dunaliella salina is a well-known microalga that accumulates valuable amounts of carotenoids. We investigated whether it could restore the metabolic equilibrium and mitigate the hepatic inflammation induced by zinc oxide nanoparticles (ZnO-NPs) using male zebrafish which were exposed to 1/5^th 96 h-LC₅₀ for 4 weeks, followed by dietary supplementation with D. salina at two concentrations (15% and 30%) for 2 weeks. Collectively, ZnO-NPs affected fish appetite, whole body composition, hepatic glycogen and lipid contents, intestinal bacterial and Aeromonas counts, as well as hepatic tumor necrosis factor- α (TNF-α). In addition, the mRNA expression of genes related to gluconeogenesis (pck1, gys2, and g6pc3), lipogenesis (srepf1, acaca, fasn, and cd36), and inflammatory response (tnf-α, tnf-β, nf-kb2) were modulated. D. salina reduced the body burden of zinc residues, restored the fish appetite and normal liver architecture, and mitigated the toxic impacts of ZnO-NPs on whole-body composition, intestinal bacteria, energy metabolism, and hepatic inflammatory markers. Our results revealed that the administration of D. salina might be effective in neutralizing the hepatotoxic effects of ZnO-NPs in the zebrafish model.

Nanotechnology has gained tremendous attention because of its crucial characteristics and wide biomedical applications. Although zinc oxide nanoparticles (ZnO-NPs) are involved in many industrial applications, researchers pay more attention to their toxic effects on living organisms. Since the olfactory epithelium is exposed to the external environment, it is considered the first organ affected by ZnO-NPs. Herein, we demonstrated the cytotoxic effect of ZnO-NPs on the olfactory organ of adult zebrafish after 60 days post-treatment. We opted for this period when fishes stop eating their diet from the aquarium, appear feeble, and cannot swim freely. Our study demonstrated that ZnO-NPs induced significant malformations of the olfactory rosettes at histological, ultrastructural, and genetic levels. At the ultrastructure level, the olfactory lamellae appeared collapsed, malformed, and twisted with signs of degeneration and loss of intercellular connections. In addition, ZnO-NPs harmed sensory receptor and ciliated cells, microvilli, rodlet, crypt, and Kappe cells, with hyper-activity of mucous secretion from goblet cells. At the genetic level, ZnO-NPs could activate the reactive oxygen species (ROS) synthesis expected by the down-regulation of mRNA expression for the antioxidant-related genes and up-regulation of DNA damage, cell growth arrest, and apoptosis. Interestingly, ZnO-NPs affected the odor sensation at 60 days post-treatment (60-dpt) more than at 30-dpt, severely damaging the olfactory epithelium and irreparably affecting the cellular repairing mechanisms. This induced a dramatically adverse effect on the cellular endoplasmic reticulum (ER), revealed by higher CHOP protein expression, that suppresses the antioxidant effect of Nrf2 and is followed by the induction of apoptosis via the up-regulation of Bax expression and down-regulation of Bcl-2 protein.