Sodium Para-aminosalicylic Acid Reverses Changes of Glutamate Turnover in Manganese-Exposed Rats

Sodium para-aminosalicylic acid (PAS-Na) has been used to treat patients with manganism, a neurological disease caused by manganese (Mn) toxicity, although the exact molecular mechanisms are yet unclear. The present study aims to investigate the effect of PAS-Na on glutamate (Glu) turnover of Mn-exp...

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Bibliographic Details
Published in:Biological trace element research 2020-10, Vol.197 (2), p.544-554
Main Authors: Li, Zhao-Cong, Wang, Fang, Li, Shao-Jun, Zhao, Lin, Li, Jun-Yan, Deng, Yue, Zhu, Xiao-Juan, Zhang, Yu-Wen, Peng, Dong-Jie, Jiang, Yue-Ming
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biotechnology
Exposure
Globus pallidus
Glutaminase
Glutamine
Hippocampus
Homeostasis
Life Sciences
Manganese
Molecular modelling
Neostriatum
Neurological diseases
Neurotoxicity
Nutrition
Oncology
Phosphates
Rodents
Sodium
Thalamus
Toxicity
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Summary:Sodium para-aminosalicylic acid (PAS-Na) has been used to treat patients with manganism, a neurological disease caused by manganese (Mn) toxicity, although the exact molecular mechanisms are yet unclear. The present study aims to investigate the effect of PAS-Na on glutamate (Glu) turnover of Mn-exposed rats. The results showed that Mn concentrations in the hippocampus, thalamus, striatum, and globus pallidus were increased in Mn-exposed rats. Moreover, the results also demonstrated that subacute Mn exposure (15 mg/kg for 4 weeks) interrupted the homeostasis of Glu by increasing Glu levels but decreasing glutamine (Gln) levels in the hippocampus, thalamus, striatum, and globus pallidus in male Sprague-Dawley rats. These effects lasted even after Mn exposure had been ceased for a period of 6 weeks. Meanwhile the main Glu turnover enzymes [Gln synthetase (GS) and phosphate-activated glutaminase (PAG)] and transporters [Glu/aspartate transporter (GLAST) and Glu transporter-1 (GLT-1)] were also affected by Mn treatment. Additionally, PAS-Na treatment recovered the aforementioned changes induced by Mn. Taken together, these results indicate that Glu turnover might be involved in Mn-induced neurotoxicity. PAS-Na treatment could promote Mn excretions and recover the changes in Glu turnover induced by Mn, and a prolonged PAS-Na treatment may be more effective.
ISSN:0163-4984
1559-0720
DOI:10.1007/s12011-019-02001-0