Vanillic acid protects against lead-induced cognitive impairment and neurodegeneration via GFAP/NRF-2 pathways in rats

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Objectives: This research aimed to unravel the ameliorative potential of vanillic acid (VA) on lead acetate (LA)-induced cortico-hippocampal neurodegeneration in Wistar rats. Methods: Forty (40) male Wistar rats (150-180 g) were randomized into four groups (A-D) (n = 10). LA and VA were freshly prepared daily for administration in dosages based on body weight (BW). Group A was administered normal saline as control; Group B received 200 mg/kg BW of LA; Group C 200 mg/kg BW of VA and 200 mg/kg BW of LA; Group D received 200 mg/kg BW of VA. The doses were selected based on existing protocols and sample size meeting the minimum estimate by power analysis. All administration was via a single daily oral dose for 45 consecutive days. Cognitive function tests including Y-maze and open field test were done. The rats were euthanized at the end of the treatment by cervical dislocation (n = 6, per group) and ketamine anesthesia + perfusion (n = 4 per group). The brains were dissected and processed for histological, biochemical, and immunohistochemistry studies. Results: Our results revealed learning and memory deficits and neuropathological changes, such as decreased neuronal cell size and the disorganization of the neuronal network within the cortex and hippocampus of LA-induced rats, when compared to the control group. However, VA had protective function by attenuating neuronal degeneration, alleviation of cognitive deficit, and aided neuroprotection of pyramidal cells and astrocytes when compared to the LA-induced rats. Discussion: VA shows protective effects against LA-induced neurodegeneration and cognitive impairment suggesting a therapeutic role in heavy metal neurotoxicity.