Acute glufosinate-based herbicide treatment in rats leads to increased ocular interleukin-1β and c-Fos protein levels, as well as intraocular pressure

Abstract

Glufosinate is a common herbicide with neurotoxic effects, leading to seizures, convulsions and memory loss. Glufosinate indirectly induces glutamate toxicity by inhibiting glutamine synthesis in astrocytes. Here, we studied the acute toxic effects of a glufosinate-based herbicide in rat optic nerve at three doses (40, 80 or 120 μM, equal to 714 or 21 mg/kg bw/day). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, calcium, as well as creatinine concentrations were analyzed after 24, 48 and 72 h treatment. Intraocular pressure (IOP) (expressed as the average of both eyes) was measured with a rebound tonometer. Interleukin-1β (IL-1β) and c-Fos expression were determined by immunohistochemistry. The results established that the glufosinate-based herbicide significantly increased IL-1β and c-Fos immunopositivity in the optic nerve (p < 0.05), concomitant with increased IOP. These results suggest that commercial formulations of glufosinate acutely affect the optic nerve.

Keywords: Glufosinate; Interleukin-1β; Intraocular pressure; c-fos.

Graphical abstract

Fig. 1

Average intraocular pressure values in both eyes of rats exposed to a glufosinate-based herbicide. Data are means ± S.D. (n = 6 rats in each group). *p < 0.05, vs control group.

Fig. 2

Effect of glufosinate-based herbicide exposure on optic nerve by immunofluorescence with anti- IL1-β and anti-c-Fos antibodies. a) Control group showing very slight level IL1-β immunopositivity, FITC b) Glufosinate-based herbicide (40 μM for 24 h, 40 μM for 48 h, 40 μM for 72 h, 80 μM for 24 h, 80 μM for 48 h, 120 μM for 24 h, 120 μM for 48 h) treated animals showing low IL1-β immunopositivity, FITC c–d) 80 μM for 72 h and 120 μM for 72 h glufosinate-based herbicide treated animals showing remarkable intense IL-1β staining in glial cells shown by arrowheads, FITC e) Control group showing very slight level c-Fos immunopositivity, (Texas-Red labeling) f) Glufosinate-based herbicide (40 μM for 24 h, 40 μM for 48 h, 40 μM for 72 h, 80 μM for 24 h, 80 μM for 48 h, 120 μM for 24 h, 120 μM for 48 h) treated animals showing low c-Fos immunopositivity, TR g–h) 80 μM for 72 h and 120 μM for 72 h glufosinate-based herbicide treated animals showing intense c-Fos immunopositivity (arrowheads), TR.