title: The in vitro effects of selenomethionine on methylmercury-induced neurotoxicity.
abstract: Selenium (Se) has been reported to reduce the severity of MeHg-induced neurological deficits. Therefore, we investigated whether 24h. preincubation or 50min. coincubation with selenomethionine (SeMet) was effective in reducing methylmercury (MeHg)-induced cytotoxicity in C6-glioma and B35-neuronal cell lines. As indicators of cytotoxicity, reduced glutathione (GSH), reactive oxygen species (ROS) and mitochondrial activity (MTT) was assessed. Measurement of GSH with the fluorescent indicator MCB-monochlorobimane indicated that in SeMet preincubated C6 cells, MeHg treatment resulted in a significant (p<0.001) decrease in GSH levels as compared to coincubation group. Treatment with SeMet did not induce any significant changes in MTT activity in either of the cell lines as compared to the MeHg group. However, the amount of MeHg-induced ROS was significantly reduced (p<0.001) after SeMet preincubation in both the cell lines. The intracellular Se content was measured with high resolution-inductively coupled plasma mass spectrometry (HR-ICPMS). In both the cell lines the intracellular Se levels increased after pre- and coincubation with 20 and 50microM SeMet. However, the preincubation group exhibited increased Se content in both the cell lines and varied (p<0.001) from coincubation group. These differences in the Se content were maintained after 10microM MeHg treatment for 50min. In C6-gliomas, the cell associated-MeHg measurements using (14)C-labeled MeHg indicated a significant increase (p<0.001) in MeHg content in preincubated cells as compared to coincubated cells. These findings provide experimental evidence that preincubation with SeMet increases Se content in cells and prevents against increased MeHg-induced ROS generation.
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Olav Kyrresgt. 3, N-7489 Trondheim, Norway.
authors.forename: Parvinder
authors.initials: P
authors.lastname: Kaur
authors.forename: Lars
authors.initials: L
authors.lastname: Evje
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.forename: Tore
authors.initials: T
authors.lastname: Syversen
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004336:Drug Antagonism; D004338:Drug Combinations; D004785:Environmental Pollutants / Q000633:toxicity*; D005562:Formazans / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008767:Methylmercury Compounds / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012645:Selenomethionine / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D004785:Environmental Pollutants; D005562:Formazans; D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; C079782:MTT formazan; D012645:Selenomethionine; D005978:Glutathione; C004925:methylmercuric chloride