Protective effects of glutathione and cysteine on the methylmercury-induced striatal dopamine release in vivo

The possible protective effects of glutathione (GSH), cysteine (CYS) and methionine (MET) on the Methylmercury (MeHg)-induced dopamine (DA) release from rat striatum were investigated using in vivo microdialysis coupled to HPLC with electrochemical detection. Intrastriatal infusion of MeHg 400 μM increased extracellular DA levels to 1941 ± 199% in terms of basal levels. Infusion of MeHg 400 μM in GSH 400 μM pretreated animals, only increased striatal DA levels to 465 ± 104%, in terms of basal levels, this increase being 76% lower than induced by MeHg alone. Conversely, the infusion of MeHg 400 μM after infusion of GSH 400 μM increased DA levels to 1019 ± 96% in terms of basal levels, this increase being 47.5% lower than that observed in MeHg non-pretreated animals. The infusion of MeHg 400 μM in CYS 400 μM -pretreated animals, increased striatal DA levels to 740 ± 149%, in terms of basal levels, this increase being 62% lower than that induced by MeHg in non-pretreated animals. The infusion of MeHg 400 μM in MET 400 μM pretreated animals increased striatal DA levels to 2011 ± 230% in terms of basal, an increase that was not significantly different from that produced by MeHg 400 μM alone. In summary, the administration of compounds containing free -SH groups prevented the MeHg-induced DA release from rat striatum, probably due to the binding of MeHg to -SH groups. This would result in a lower metal availability to interact with -SH membrane proteins groups, which would decrease MeHg ability to interact with DA transporter.