title: Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity.
abstract: Citrinin, a natural mycotoxin that is found in fermented foods, is known as a cytotoxin and nephrotoxin. Exposure to high doses of citrinin result in apoptosis; however, the effects of low doses are not fully understood. Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and other neurodegenerative diseases. Here, we show the neuroprotective effect of low doses of citrinin against glutamate-induced excitotoxicity. We examined the effect of citrinin exposure on glutamate-induced cell death in cultured rat cortical neurons under two conditions: simultaneous treatment with citrinin 0.1 to 1,000 nM and glutamate (30 μM) for 1, 3 hr; the same simultaneous treatment for 3 hr after pretreatment with citrinin for 21 hr. Both the MTT and immunocytochemical assay showed significant neuroprotective effects at several doses and exposure times tested. All concentrations of citrinin tested showed no remarkable cell death following 14-day exposure, and no marked alterations to synapses. These data suggest that low doses of citrinin can be used as a neuroprotective agent against glutamate-induced excitotoxicity without additional harmful cellular alterations.
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Iguchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamisuki
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.forename: Teiichi
authors.initials: T
authors.lastname: Furuichi
authors.forename: Yo
authors.initials: Y
authors.lastname: Shinoda
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D002953:Citrinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000633:toxicity*; D009183:Mycotoxins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D005971:Glutamates; D009183:Mycotoxins; D018696:Neuroprotective Agents; D002953:Citrinin