Boric acid protects against glyphosate-induced neurotoxicity by modulating oxidative stress, inflammation, apoptosis, and autophagy pathways in the rat brain

Abstract

Background

Glyphosate (GLY) is a widely used herbicide with increasing evidence of neurotoxic effects. Boric acid (BA), a trace element, has shown potential antioxidant and anti-inflammatory properties, but its role in GLY-induced neurotoxicity remains unexplored.

Objective

This study aimed to investigate the neuroprotective effects of boric acid against glyphosate-induced brain toxicity in rats through behavioral, biochemical, molecular, and histological evaluations.

Materials and methods

Twenty-eight adult rats were divided into four groups (n = 7): Control, BA (100 mg/kg), GLY (150 mg/kg), and GLY+BA. All treatments were given orally for 7 days. Behavioral assessments were performed using the Elevated Plus Maze and Locomotor Activity Test. Oxidative stress markers (MDA, GSH, SOD, CAT, GPx), apoptotic markers (Bax, Bcl-2, Caspase-3), and inflammatory proteins (TNF-α, IL-1β, IL-6, COX-2, TLR-4, NF-κB) were analyzed. Iba-1 and GFAP were assessed by Western blot, while histopathological and immunohistochemical evaluations included 8-OHdG, TLR2, and LC3A/B.

Results

GLY exposure led to significant behavioral deficits, oxidative stress, inflammation, apoptosis, and neuronal damage. BA co-treatment significantly improved behavioral performance, restored antioxidant balance, downregulated pro-inflammatory and apoptotic markers, and reduced glial activation and histological damage.

Conclusion

Boric acid exerts neuroprotective effects against GLY-induced neurotoxicity, likely via modulation of oxidative stress, inflammation, apoptosis, and autophagy pathways, supporting its therapeutic potential in chemical-induced brain injury.