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

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Abstract

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.

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Acknowledgments

The authors thank Dr. Richard B. Mailman from Pennsylvania State University-Penn State Health Milton S. Hershey Medical Center for his useful suggestions. The authors thank Prof. Guo-Dong Lu from Guangxi Medical University and Dr. Leslie Jellen from Pennsylvania State University-Penn State Health Milton S. Hershey Medical Center for their revision of the manuscript for grammar, style, and syntax.

Funding

This study was funded by grants from the National Natural Science Foundation of China (NSFC 81460505).

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Author notes

  1. Zhao-Cong Li, Fang Wang and Shao-Jun Li contributed equally to this work.

Authors and Affiliations

  1. Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China

    Zhao-Cong Li, Fang Wang, Shao-Jun Li, Lin Zhao, Jun-Yan Li, Yue Deng, Xiao-Juan Zhu, Yu-Wen Zhang, Dong-Jie Peng & Yue-Ming Jiang

  2. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China

    Zhao-Cong Li, Shao-Jun Li, Lin Zhao, Jun-Yan Li, Yue Deng, Xiao-Juan Zhu, Yu-Wen Zhang, Dong-Jie Peng & Yue-Ming Jiang

  3. Institute of Toxicology, Guangxi Center for Disease Prevention and Control, Nanning, 530028, China

    Fang Wang

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  1. Zhao-Cong Li
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Li, ZC., Wang, F., Li, SJ. et al. Sodium Para-aminosalicylic Acid Reverses Changes of Glutamate Turnover in Manganese-Exposed Rats. Biol Trace Elem Res 197, 544–554 (2020). https://doi.org/10.1007/s12011-019-02001-0

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