Abstract
Since glufosinate irreversibly inhibits glutamine synthetase, leading to intracellular accumulation of ammonia, hyperammonemia is considered one of the main mechanisms of glufosinate ammonium toxicity in humans. However, whether hyperammonemia causes neurotoxicity has not yet been studied. Therefore, the purpose of this study was to determine whether the serum ammonia level is elevated before the development of neurotoxicity. In this retrospective observational study, we analyzed data from consecutive patients diagnosed with acute glufosinate ammonium poisoning. The primary outcome was the development of neurotoxicity following the poisoning. Patients who developed neurotoxicity were characterized by higher initial ammonia levels compared to patients without neurotoxicity (121.0 µg/dL [87.0; 141.0] vs 83.0 µg/dL [65.0; 119.0], p < 0.01). However, there was no increase in ammonia levels over time in both the asymptomatic and neurotoxicity groups when serial serum ammonia levels were examined from emergency department admission to hospital discharge. In addition, there was no statistically significant difference between the peak ammonia levels in the asymptomatic group and the peak ammonia levels before symptom onset in the neurotoxicity group (135.0 µg/dL [109.0; 158.0] vs 144.0 µg/dL [120.0; 189.0], p = 0.15). Following the onset of neurotoxicity, the serum ammonia level increased significantly (125.0 [111.0; 151.0] µg/dL to 148.0 [118.0; 183.0] µg/dL, p < 0.01). In conclusion, hyperammonemia cannot be assumed as the cause of neurotoxicity in glufosinate ammonium poisoning and further research is needed to examine the exact mechanism of GA poisoning.
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Conceptualization: Yong Soo Cho.
Data curation: Joochan Kim.
Formal analysis: Seok jin Ryu.
Funding acquisition: None.
Investigation: Byung Kook Lee.
Methodology: Byung Kook Lee.
Software: Dong Hun Lee.
Supervision: Byeong Jo Chun.
Validation: Jeong Mi Moon.
Visualization: Dong ki Kim.
Writing—original draft: Joochan Kim.
Writing—review and editing: Yong Soo Cho.
Approval of final manuscript: all authors.
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Kim, J., Cho, Y.S., Chun, B.J. et al. The trend of ammonia levels in patients with glufosinate ammonium poisoning with respect to neurotoxicity. Naunyn-Schmiedeberg's Arch Pharmacol 396, 525–531 (2023). https://doi.org/10.1007/s00210-022-02327-y
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DOI: https://doi.org/10.1007/s00210-022-02327-y