Neuroprotective Effect of Low-Dose of Vitamin A on the Prefrontal Cortex of Methamphetamine Induced Adult Male Wistar Rats

Abstract

Methamphetamine is a potent psychostimulant known to induce oxidative stress and neurodegeneration, particularly in the prefrontal cortex, which is responsible for executive and cognitive functions. Vitamin A, an essential antioxidant, may offer neuroprotection by modulating oxidative balance and preserving neuronal integrity. This study investigated the effect of low-dose vitamin A on the prefrontal cortex of adult male Wistar rats exposed to toxic doses of methamphetamine. Twenty adult male Wistar rats were divided into four groups consisting of five rats for each group. Group A received distilled water and normal feed; Group B received 10 mg/kg methamphetamine; Group C received 1.2 mg/kg vitamin A; and Group D received 10 mg/kg of methamphetamine and 1.2 mg/kg vitamin A. Treatment lasted for 28 days. Body weight, oxidative stress biomarkers [malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD)], and behavioral performance using the Morris Water Maze test were assessed. Data were analyzed using one-way ANOVA and considered statistically significant when P <0.05. Methamphetamine exposure (Group B) led to significant weight loss (p = 0.001), elevated MDA levels, and reduced GSH and SOD activities, indicating oxidative stress. Co-administration of vitamin A (Group D) significantly improved antioxidant enzyme levels (p < 0.05) and reduced escape latency in the Morris Water Maze test, reflecting enhanced cognitive performance. Histological examination of the prefrontal cortex revealed that vitamin A mitigated methamphetamine-induced neuronal necrosis, cytoplasmic vacuolation, and perivascular edema, suggesting structural recovery. In conclusion, low-dose vitamin A may exert neuroprotective effects against methamphetamine-induced oxidative damage and cognitive impairment in the prefrontal cortex of adult male Wistar rats. These findings support the potential therapeutic role of vitamin A in managing methamphetamine-induced neurotoxicity.