The treatment effects of HET0016 on demyelinating Mice induced by cuprizone

Cytochrome P450s (CYP) ω-hydroxylase and its metabolites 20 - hydroxyeicosatetraenoic acid (20-HETE) play an important role in the central nervous system disorders. The purpose of this study was to determine the effects of the 20-HETE inhibitor, HET0016, on myelin sheath after demylination in mice. Methods: We have studied the impact of HET0016 on remyelination using the toxic cuprizone model. Animals were assigned randomly to various groups and injected intraperitoneally with 10% lecithin or 2.0 and 0.2 mg/kg of HET0016 per day in 2 weeks. The animals were killed and the brains were reserved. We investigated spatial memory of mice using the Y-maze. We observed the myelin of corpus callosum by histochemical staining. Results: there were no significant differences in body weight, food intake and water intake between the model group and HET0016 (2.0mg/kg, 0.2mg/kg) group; spatial memory improved significantly in HET0016 (0.2mg/kg, 2.0mg/kg) group compared with model group; corpus callosum structure was significantly remyelinated after 2 weeks by HET0016 treatment. Conclusion: HET0016, a selective inhibitor of CYP ω-hydroxylase, has potent therapeutic effect on multiple sclerosis mice.