title: Methionine stimulates motor impairment and cerebellar mercury deposition in methylmercury-exposed mice.
abstract: Methylmercury (MeHg) is a highly toxic environmental contaminant that produces neurological and developmental impairments in animals and humans. Although its neurotoxic properties have been widely reported, the molecular mechanisms by which MeHg enters the cells and exerts toxicity are not yet completely understood. Taking into account that MeHg is found mostly bound to sulfhydryl-containing molecules such as cysteine in the environment and based on the fact that the MeHg-cysteine complex (MeHg-S-Cys) can be transported via the L-type neutral amino acid carrier transport (LAT) system, the potential beneficial effects of L-methionine (L-Met, a well known LAT substrate) against MeHg (administrated as MeHg-S-Cys)-induced neurotoxicity in mice were investigated. Mice were exposed to MeHg (daily subcutaneous injections of MeHg-S-Cys, 10 mg Hg/kg) and/or L-Met (daily intraperitoneal injections, 250 mg/kg) for 10 consecutive days. After treatments, the measured hallmarks of toxicity were mostly based on behavioral parameters related to motor performance, as well as biochemical parameters related to the cerebellar antioxidant glutathione (GSH) system. MeHg significantly decreased motor activity (open-field test) and impaired motor performance (rota-rod task) compared with controls, as well as producing disturbances in the cerebellar antioxidant GSH system. Interestingly, L-Met administration did not protect against MeHg-induced behavioral and cerebellar changes, but rather increased motor impairments in animals exposed to MeHg. In agreement with this observation, cerebellar levels of mercury (Hg) were higher in animals exposed to MeHg plus L-Met compared to those only exposed to MeHg. However, this event was not observed in kidney and liver. These results are the first to demonstrate that L-Met enhances cerebellar deposition of Hg in mice exposed to MeHg and that this higher deposition may be responsible for the greater motor impairment observed in mice simultaneously exposed to MeHg and L-Met.
authors.affiliation: a Departamento de Bioquímica, Centro de Ciências Biológicas , Universidade Federal de Santa Catarina , Florianópolis , Santa Catarina , Brazil.
authors.forename: Luciana T
authors.initials: LT
authors.lastname: Zimmermann
authors.forename: Danúbia B
authors.initials: DB
authors.lastname: dos Santos
authors.forename: Dirleise
authors.initials: D
authors.lastname: Colle
authors.forename: Alessandra A
authors.initials: AA
authors.lastname: dos Santos
authors.forename: Mariana A
authors.initials: MA
authors.lastname: Hort
authors.forename: Solange C
authors.initials: SC
authors.lastname: Garcia
authors.forename: Lucas Paines
authors.initials: LP
authors.lastname: Bressan
authors.forename: Denise
authors.initials: D
authors.lastname: Bohrer
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002531:Cerebellum / Q000737:chemistry* / Q000378:metabolism; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D004334:Drug Administration Schedule; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000494:pharmacology*; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D011897:Random Allocation
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; C030589:methylmercury cysteine; D008715:Methionine; D005979:Glutathione Peroxidase; D005978:Glutathione; D003545:Cysteine