A novel synthetic chemical entity (UPEI-800) is neuroprotective in vitro and in an in vivo rat model of oxidative stress

Clinical and Experimental Pharmacology & Physiology
Tarek M SalehAlaa S Abd-El-Aziz

Abstract

In this study, we tested a novel synthetic pyrazole-containing compound, 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile (APPC), as an antioxidant in both in vitro and in vivo models of oxidative stress. In addition, the utility of covalently combining APPC with another well-established antioxidant, lipoic acid (LA), was also tested in both models. The in vitro results demonstrated that pretreatment with APPC in a mixed neuronal-glial culture exposed to oxygen-glucose deprivation (OGD) followed by reoxygenation-refeeding, resulted in significant neuroprotection at concentrations between 2.5 to 25 μmol/L. In contrast, LA was not neuroprotective following OGD alone or following reoxygenation-refeeding. However, the synthetic covalent combination of APPC with LA, named "UPEI-800", resulted in significant neuroprotection at concentrations between 0.027 and 2.7 μmol/L (100-fold more potent than APPC alone), an effect shown to be correlated with increased cellular antioxidant capacity. Further, in an in vivo model of ischaemia-reperfusion injury following transient occlusion of the middle cerebral artery (tMCAO), both APPC (0.1 and 1.0 mg/kg) and UPEI-800 (1×10-3  mg/kg) provided significant neuroprotection. Consistent with the in vitro ...Continue Reading

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Citations

May 26, 2018·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Fatma GuesmiAhmed Landoulsi
Jun 4, 2021·CNS & Neurological Disorders Drug Targets·Subham DasAlex Joseph

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