Influence of high-dose sodium benzoate on lipopolysaccharide-induced neurobehavioral impairment, oxido-inflammatory brain damage, and cholinergic dysfunction in rats

Abstract

Sodium benzoate (SB) is a commonly utilized food preservative in the food business. Nonetheless, apprehensions regarding its impact on the brain have garnered worldwide attention. Consequently, we examined the effect of SB on lipopolysaccharide (LPS)-induced neurotoxicity in rats. Twenty-eight male Wistar rats were randomly assigned to four groups: Group 1 (Control, distilled water), Group 2 (SB, 600 mg/kg), Group 3 (LPS, 250 μg/kg/day), and Group 4 (LPS + SB; LPS, 250 μg/kg + SB, 600 mg/kg). SB was administered orally for 14 days, whereas LPS was injected intraperitoneally for 7 days. Upon completion of the treatment, locomotor, motor, and exploratory behaviors were assessed, followed by biochemical, molecular, and histological analyses of the rat brain. Results indicated that SB exacerbated LPS-induced impairments in exploratory behavior and locomotion in rats. Furthermore, SB intensified LPS-induced oxidative stress and cholinergic impairment, as evidenced by reduced levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione-S-transferase (GST) activity, alongside an increase in malondialdehyde (MDA) and acetylcholinesterase (AChE) activity in brain tissue. Similarly, exposure to SB led to a substantial elevation in the levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), as well as nitric oxide (NO) and myeloperoxidase (MPO) activity in the rat brain. Additionally, histological examination reveals degenerative neurons in the cerebellum, cortex, and hippocampus CA1 and CA3 areas. The outcomes of this study indicate that the co-administration of SB with LPS exacerbated the neurotoxic damage caused by LPS in the rat brain.