4-Methylumbeliferone Treatment at a Dose of 1.2 g/kg/Day Is Safe for Long-Term Usage in Rats

4-methylumbelliferone (4MU) has been suggested as a potential therapeutic agent for a wide range of neurological diseases. The current study aimed to evaluate the physiological changes and potential side effects after 10 weeks of 4MU treatment at a dose of 1.2 g/kg/day in healthy rats, and after 2 months of a wash-out period. Our findings revealed downregulation of hyaluronan (HA) and chondroitin sulphate proteoglycans throughout the body, significantly increased bile acids in blood samples in weeks 4 and 7 of the 4MU treatment, as well as increased blood sugars and proteins a few weeks after 4MU administration, and significantly increased interleukins IL10, IL12p70 and IFN gamma after 10 weeks of 4MU treatment. These effects, however, were reversed and no significant difference was observed between control treated and 4MU-treated animals after a 9-week wash-out period

Using ferromagnetic nanoparticles with low Curie temperature for magnetic resonance imaging-guided thermoablation

Vít Herynek,1 Karolína Turnovcová,2 Pavel Veverka,3 Tereza Dědourková,4,5 Pavel Žvátora,6 Pavla Jendelová,2 Andrea Gálisová,1 Lucie Kosinová,7 Klára Jiráková,2 Eva Syková2 1MR-Unit, Radiodiagnostic and Interventional Radiology Department, Institute for Clinical and Experimental Medicine, Prague, 2Department of Neuroscience, Institute of Experimental Medicine, 3Department of Magnetics and Superconductors, Institute of Physics, Czech Academy of Sciences, Prague, 4Department of Inorganic Technology, Faculty of Chemical Technology, University of Pardubice, 5SYNPO, akciová společnost, Pardubice, 6Department of Analytical Chemistry, Institute of Chemical Technology, 7Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Introduction: Magnetic nanoparticles (NPs) represent a tool for use in magnetic resonance imaging (MRI)-guided thermoablation of tumors using an external high-frequency (HF) magnetic field. To avoid local overheating, perovskite NPs with a lower Curie temperature (Tc) were proposed for use in thermotherapy. However, deposited power decreases when approaching the Curie temperature and consequently may not be sufficient for effective ablation. The goal of the study was to test this hypothesis. Methods: Perovskite NPs (Tc =66°C–74°C) were characterized and tested both in vitro and in vivo. In vitro, the cells suspended with NPs were exposed to a HF magnetic field together with control samples. In vivo, a NP suspension was injected into a induced tumor in rats. Distribution was checked by MRI and the rats were exposed to a HF field together with control animals. Apoptosis in the tissue was evaluated. Results and discussion: In vitro, the high concentration of suspended NPs caused an increase of the temperature in the cell sample, leading to cell death. In vivo, MRI confirmed distribution of the NPs in the tumor. The temperature in the tumor with injected NPs did not increase substantially in comparison with animals without particles during HF exposure. We proved that the deposited power from the NPs is too small and that thermoregulation of the animal is sufficient to conduct the heat away. Histology did not detect substantially higher apoptosis in NP-treated animals after ablation. Conclusion: Magnetic particles with low Tc can be tracked in vivo by MRI and heated by a HF field. The particles are capable of inducing cell apoptosis in suspensions in vitro at high concentrations only. However, their effect in the case of extracellular deposition in vivo is questionable due to low deposited power and active thermoregulation of the tissue. Keywords: perovskite nanoparticles, hyperthermia, high-frequency magnetic field, MRI, tumor ablatio