Abstract:
[Objective] To probe the antagonistic effect of alpha lipoic acid (α-LA) on the glutamate metabolism and transport disrupted by methylmercury.
[Methods] Twenty-four Wistar rats were randomly divided into 4 groups by weight (6 rats per group including 3 male and 3 female):a control group, a low-and a high-dose methylmercury groups, and an α-LA pretreatment group. The control and the methylmercury groups were treated by subcutaneous injection with 0.9% NaCl, and the pretreatment group was injected with 35 μmol/kg α-LA. Two hours later, the control group was peritoneally injected with 0.9% NaCl; the two methylmercury groups and the pretreatment group were peritoneally injected with 4, 12, and 12 μmol/kg CH3HgCl, respectively. The administration frequency of CH3HgCl was every 2 days for the α-LA pretreatment group, and every day (that was 5 times/week) for the two methylmercury groups. The administration protocol lasted for 4 weeks. Twenty-four hours after the last administration, the cerebral cortex was harvested to prepare 5% and 10% homogenates; the concentrations of Hg, Glu, Gln, as well as the activity of phosphate activated glutaminase (PAG), glutamine synthetase (GS), Na+-K+-ATPase, and Ca2+-ATPase were determined.
[Results] In comparison with the control group, the concentrations of mercury[(17.72& #177;1.36) μg/g tissue], Glu[(71.57& #177;10.87) μmol/g protein], and the PAG activity[(31.26& #177;4.38) μmol/(min& #183;g protein)] in the brain tissue of high-dose methylmercury treated rats were significantly increased (P< 0.01); the concentration of Gln[(0.15& #177;0.04) μmol/g protein] and the GS activity[(23.89& #177;3.60) U/g protein] were significantly decreased (P< 0.01); the activities of Na+-K+-ATPase[(4.03& #177;0.57) μmol/(h& #183;mg protein)] and Ca2+-ATPase[(2.21& #177;0.62) μmol/(h& #183;mg protein)] were significantly lowered (P< 0.01). The above-mentioned indicators' alterations were smaller in the α-LA treated group:the concentrations of Glu[(63.02& #177;3.33) μmol/g protein] and Gln[(0.20& #177;0.05) μmol/g protein]; activities of PAG[(26.03& #177;3.88) μmol/(min& #183;g protein)], GS[(34.05& #177;4.23) U/g protein], Na+-K+-ATPase[(5.52& #177;1.16) μmol/(h& #183;mg protein)],and Ca2+-ATPase[(3.27& #177;0.60) μmol/(h& #183;mg protein)]. The differences of the above indicators between the α-LA treated group and the high-dose methylmercury group showed statistical significance (P< 0.01 or P< 0.05).
[Conclusion] α-LA can serve as a protective agent against glutamate metabolism disrupted by methylmercury.
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