No abstract

Nanomedicine offers a promising tool for therapies of brain diseases, but they may be associated with potential adverse effects. The aim of this study was to investigate the uptake of silica-nanoparticles engineered for laser-tissue soldering in the brain using SH-SY5Y cells, dissociated and organotypic slice cultures from rat hippocampus. Nanoparticles were predominantly taken up by microglial cells in the hippocampal cultures but nanoparticles were also found in differentiated SH-SY5Y cells. The uptake was time- and concentration-dependent in primary hippocampal cells. Transmission electron microscopy experiments demonstrated nanoparticle aggregates and single particles in the cytoplasm. Nanoparticles were found in the endoplasmic reticulum, but not in other cellular compartments. Nanoparticle exposure did not impair cell viability and neuroinflammation in primary hippocampal cultures at all times investigated. Neurite outgrowth was not significantly altered in SH-SY5Y cells, but the neuronal differentiation markers indicated a reduction in neuronal differentiation induction after nanoparticle exposure.

Polycyclic aromatic hydrocarbons (PAHs) are immunotoxicants in fish. In mammals, phase I metabolites are believed to be critically involved in the immunotoxicity of PAHs. This mechanism has been suggested for fish as well. The present study investigates the capacity of immune organs (head kidney, spleen) of rainbow trout, Oncorhynchus mykiss, to metabolize the prototypic PAH, benzo [a]pyrene (BaP). To this end, we analyzed 1) the induction of enzymatic capacity measured as 7-ethoxyresorufin-O-deethylase (EROD) activity in immune organs compared with liver, 2) the organ profiles of BaP metabolites generated in vivo, and 3) rates of microsomal BaP metabolite production in vitro. All measurements were done for control fish and for fish treated with an intraperitoneal injection of 15 mg BaP/kg body weight. In exposed trout, the liver, head kidney, and spleen contained similar levels of BaP, whereas EROD induction differed significantly between the organs, with liver showing the highest induction factor (132.83), followed by head kidney (38.43) and spleen (1.43). Likewise, rates of microsomal metabolite formation experienced the highest induction in the liver of BaP-exposed trout, followed by the head kidney and spleen. Microsomes from control fish displayed tissue-specific differences in metabolite production. In contrast, in BaP-exposed trout, microsomes of all organs produced the potentially immunotoxic BaP-7,8-dihydrodiol as the main metabolite. The findings from this study show that PAHs, like BaP, are distributed into immune organs of fish and provide the first evidence that immune organs possess inducible PAH metabolism leading to in situ production of potentially immunotoxic PAH metabolites.