Characterization of seizures induced by acute exposure to an organophosphate herbicide, glufosinate-ammonium

Abstract

Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection.

Seizures in patients with acute pesticide intoxication, with a focus on glufosinate ammonium

“…3 Although glufosinate ammonium herbicides are considered safe when used properly, 4 many clinical toxicologists have reported that the ingestion of a large amount of glufosinate ammonium can cause convulsions. 5 –8…”

“…A combination of clinical studies and in vitro studies has provided a growing consensus that seizure is a common complication of glufosinate herbicide intoxication. 5,11…”

Clinical features of acute glufosinate ammonium and initial serum ammonia and CK-MB as early predictors of unfavorable prognosis

“…GA's primary mechanism involves the inhibition of the glutamine synthetase enzyme, resulting in an increase in blood ammonia levels and subsequent damage to various organs, primarily the nervous system, causing tissue necrosis [4][5][6]. However, many patients suffer from sudden respiratory failure, coma, convulsions, and seizures during hospitalization, despite presenting with unremarkable symptoms or signs upon arrival at the emergency department [7][8][9]. Many clinician, particularly emergency physicians, would be hopefully nd out some factors to predict unfavorable outcomes of GA poisoning early.…”

Clinical features and prognostic factors of acute glufosinate ammonium

“…GA's primary mechanism involves the inhibition of the glutamine synthetase enzyme, resulting in an increase in blood ammonia levels and subsequent damage to various organs, primarily the nervous system, causing tissue necrosis [4][5][6]. However, many patients suffer from sudden respiratory failure, coma, convulsions, and seizures during hospitalization, despite presenting with unremarkable symptoms or signs upon arrival at the emergency department [7][8][9]. Many clinician, particularly emergency physicians, have insu cient knowledge about the harmful effects of GA poisoning.…”