1-1-diphenyl-2-picrylhydrazyl and Epilepsy

There are numerous studies supporting the contribution of oxidative stress to the pathogenesis of epilepsy. Prolonged oxidative stress is associated with the overexpression of ATP-binding cassette transporters, which results in antiepileptic drugs resistance. During our studies, three 1,2,4-triazole-3-thione derivatives were evaluated for the antioxidant activity and anticonvulsant effect in the 6 Hz model of pharmacoresistant epilepsy. The investigated compounds exhibited 2-3 times more potent anticonvulsant activity than valproic acid in 6 Hz test in mice, which is well-established preclinical model of pharmacoresistant epilepsy. The antioxidant/ROS scavenging activity was confirmed in both single-electron transfer-based methods (DPPH and CUPRAC) and during flow cytometric analysis of total ROS activity in U-87 MG cells. Based on the enzymatic studies on human carbonic anhydrases (CAs), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), one can assume that the herein investigated drug candidates will not impair the cognitive processes mediated by CAs and will have minimal off-target cholinergic effects.

Topics: Acetylcholinesterase; Animals; Anticonvulsants; Antioxidants; Biphenyl Compounds; Butyrylcholinesterase; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Cell Line, Tumor; Cell Survival; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Epilepsy; Humans; Mice; Models, Molecular; Molecular Structure; Oxidative Stress; Picrates; Reactive Oxygen Species; Structure-Activity Relationship; Triazoles

The antioxidant effect of Fructus Momordicae extract, FME (mogrosides 75 approximately 80%), was studied. FME reduced the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and scavenged superoxide radicals (O2-) generated by a hypoxanthine and xanthine oxidase system. It also scavenged hydroxyl radicals (.OH) generated by Fenton reaction. In addition, FME inhibited Fe(II) induced lipid peroxidation in rat cortex homogenates in a dose-dependent manner, as indicated by decreased thiobarbituric acid-reactive substances (TBARS) formation. Oral administration of FME inhibited TBARS and malonaldehyde (MDA) formation in the ipsilateral cortex 30 min after iron-salt injection into the left cortex of rat. FME showed inhibitory effect on 4-hydroxy-2(E)-nonenal (4-HNE) formation induced by Fe(III) injection into the rat cortex. These data suggest that Fructus Momordicae extract has an antioxidant activity against free radicals and lipid peroxidation.

Topics: Animals; Antioxidants; Bepridil; Biphenyl Compounds; Cerebral Cortex; Drugs, Chinese Herbal; Epilepsy; Free Radical Scavengers; Hydroxyl Radical; In Vitro Techniques; Lipid Peroxidation; Male; Malondialdehyde; Picrates; Rats; Rats, Wistar; Superoxides; Thiobarbituric Acid Reactive Substances