Effect of sodium para-aminosalicylic on concentrations of amino acid neurotransmitters in basal ganglia of manganese-exposed rats

Abstract

To probe the effect of sodium para-aminosalicylate (PAS-Na) on concentration of amino acid neurotransmitters including glutamate (Glu), glutamine (Gln), glycine (Gly) and gamma-aminobutyric acid (GABA) in basal ganglia of subacute manganese (Mn)-exposed rats. Forty Sprague-Dawley male rats were randomly divided into the control, Mn-exposed, low dose PAS-Na (L-PAS) and high dose PAS-Na (H-PAS) groups. Rats in experiment groups received daily intraperitoneally injections of manganese chloride (MnCl₂ · 4H₂O, 15 mg/kg), while rats in control group received daily intraperitoneally injections of normal saline (NS), all at 5 days/week for 4 weeks. Then the rats in PAS groups followed by a daily subcutaneously dose of PAS-Na (100 and 200 mg/kg as the L-PAS and H-PAS groups, respectively) for another 3 and 6 weeks; while the rats in Mn-exposed and control group received NS. The concentrations of Glu, Gln, Gly and GABA in basal ganglia of rat was detected by the high performance liquid chromatography fluorescence detection technique. After treating with PAS-Na for 3 weeks, the concentration of Gly in the Mn-exposed rats decreased to (0.165 ± 0.022) µmol/L (control = (0.271 ± 0.074) µmol/L, Mn vs control, t = 4.65, P < 0.05). After the further 6-week therapy with PAS-Na, the concentrations of Glu, Gln, Gly in the Mn-exposed rats were lower than those of the control rats ((0.942 ± 0.121), (0.377 ± 0.070), (0.142 ± 0.048), (1.590 ± 0.302), (0.563 ± 0.040), (0.247 ± 0.084) µmol/L; t = 7.72, 5.85, 4.30, P < 0.05); and also lower than in L-PAS and H-PAS groups, whose concentrations were separately (1.268 ± 0.124), (1.465 ± 0.196), (0.497 ± 0.050), (0.514 ± 0.103), (0.219 ± 0.034) µmol/L (L-PAS Glu and Gln vs Mn, t = 3.87, 3.77, P < 0.05; H-PAS Glu, Gln and Gly vs Mn, t = 6.78, 4.70, 3.42, P < 0.05). The toxic effect of manganese on Glu, Gln and Gly in basal ganglia of Mn-exposed rats is obvious, especially appears earlier on Gly. The toxic effect still continues to develop when relieved from the exposure. PAS-Na may play an antagonism role in toxic effect of manganese on concentration of Glu, Gln and Gly in basal ganglia of Mn-exposed rats.