Abstract
Background & Objective: The simvastatin (Sim) is a lipophilic statin and can cross the blood-brain barrier. The role of vitamin D (Vit D) in brain development and function has been supported over the past decade. This study aimed to evaluate the effect of simvastatin on memory and anxiety levels in healthy male rats.
 Materials & Methods: In this experimental study, 36 male Wistar rats weighing 250-300 g were randomly divided into six groups (n=6) including control, Vit D (5 µg/kg/day; IP), Simvastatin (1 mg/kg/day; orally) (SimL), Simvastatin (10 mg/kg/day; orally) (SimH), SimL + Vit D and SimH + Vit D. After 28 days, at the end of the treatment, the behavioral anxiety test and memory behavioral test were performed. Then, the rats were euthanized, and oxidative stress markers of the brain, serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and cholesterol levels were investigated. Data were analyzed by SPSS 24 software and Tukey’s test.
 Results: Co-administration of simvastatin and vitamin D significantly increased working memory, catalase activity, total antioxidant capacity, HDL-C, and decreased anxiety levels, malondialdehyde (MDA) concentration, cholesterol, and LDL-C compared to the control group (p<0.05). However, the administration of simvastatin and vitamin D alone did not significantly change the mentioned parameters compared to the control group (p>0.05).
 Conclusion: Co-administration of simvastatin and vitamin D can improve brain function by reducing oxidative stress and cholesterol levels.
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