title: Metrifonate alters antioxidant levels and caspase activity in cerebral cortex of Wistar rats.
abstract: Metrifonate (trichlorfon) is an inhibitor of acetylcholinesterase (AChE). It was used as an Alzheimer's disease (AD) drug; however, the application was withdrawn due to adverse effects. Implication of metrifonate for the antioxidant status and regulation of apoptotic processes was evaluated in the present study. Wistar rats (six per group) were exposed subcutaneously to either 60 or 120 mg/kg of body weight of metrifonate and compared with the controls treated with saline only. Cerebral cortex and liver tissues were collected from animals 40 min after exposure. Activities of AChE, glutathione reductase, glutathione-S-transferase, caspase 3, total protein level, thiobarbituric acid reactive substances, reduced glutathione level and ferric reducing antioxidant power (FRAP) were assayed in the tissue samples. Metrifonate had only lower impact on oxidative stress in the liver. Cerebral cortex tissues had decreased AChE and increased caspase 3 activities as well as the FRAP level. Owing to the novel findings, suitability of metrifonate for AD therapy is discussed.
authors.affiliation: Faculty of Military Health Sciences, University of Defence, Trebesska, Hradec Kralove , Czech Republic. miroslav.pohanka@gmail.com
authors.forename: Miroslav
authors.initials: M
authors.lastname: Pohanka
authors.forename: Ladislav
authors.initials: L
authors.lastname: Novotny
authors.forename: Jiri
authors.initials: J
authors.lastname: Pikula
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D051381:Rats; D014236:Trichlorfon / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D014236:Trichlorfon; D020169:Caspases