Putative agmatinase inhibitor for hypoxic-ischemic new born brain damage.

摘要: Agmatine is an endogenous brain metabolite, decarboxylated arginine, which has neuroprotective properties when injected intraperitoneally (i.p.) into rat pups following hypoxic-ischemia. A previous screen for compounds based on lysates containing agmatinase with assistance from computational chemistry, led to piperazine-1-carboxamidine as a putative inhibitor. Herein, the of are described both in vitro and vivo. Organotypic entorhinal-hippocampal slices were firstly prepared 7-day-old exposed atmospheric oxygen depletion 3 h. Upon reoxygenation, treated or agmatine (50 μg/ml agents), saline, 15 h later propidium iodine was used stain. Piperazine-1-carboxamidine produced substantial protection compared post-reoxygenated saline-treated controls. An vivo model involved surgical right carotid ligation followed by exposure hypoxic-ischemia (8 % oxygen) 2.5 h. at 50 mg/kg i.p. given 15 min post-reoxygenation continued twice daily 3 days. Cortical levels elevated (+28.5 %) treatment no change arginine its other major metabolites. Histologic staining anti-Neun monoclonal antibody also revealed neuroprotection CA1-3 layers hippocampus. Until endpoint 22 days age, adverse events observed pups’ body weights, rectal temperatures, prompted ambulation. therefore appears be agent new category,