Neuroprotective Effects of Bexarotene and Icariin in a Diabetic Rat Model

Objective Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder affecting over 400 million people globally, is increasingly recognized for its detrimental impact on the central nervous system. T2DM is linked to neurodegenerative diseases like Alzheimer's and vascular dementia. This study investigates the neuroprotective effects of bexarotene and icariin in a T2DM rat model, focusing on brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and neurofilament-light chain (NfL) levels. Methods Before the study, rats underwent fasting blood glucose tests, lipid profile assessments, and general health evaluations, followed by a high-fat diet for two weeks and a single streptozotocin dose (35 mg/kg). Rats with fasting blood glucose levels ≥250 mg/dl were classified as diabetes mellitus (DM) and continued on the high-fat diet throughout the experiment. Forty-seven male Wistar Albino rats were divided into six groups: a healthy control group, a DM control group, a DM group treated with bexarotene, a DM group treated with icariin, and two DM groups treated with combinations of low and high doses of bexarotene and icariin. After the 45-day treatment, blood samples were collected under thiopental sodium anesthesia, with HbA1c (glycosylated hemoglobin) and hematological parameters analyzed within eight hours, and serum stored at -80°C for further analysis. The animals were then euthanized, and brain tissues were harvested, frozen, and stored at -80°C until further examination. Brain tissues were analyzed for BDNF, GFAP, and NfL levels using ELISA (enzyme-linked immunosorbent assay). For comparing multiple groups, the Kruskal-Wallis test was applied to nonparametric data, and one-way ANOVA was used for parametric data, followed by Bonferroni's post hoc test for pairwise comparisons. Statistical significance was determined with two-tailed tests at p < 0.05. Results Significant changes in GFAP levels were observed across groups (p < 0.001). The DM control group showed the highest GFAP levels, while treatment groups exhibited reductions. The DM control group also showed the highest BDNF levels, while treatment groups exhibited reductions. The DM control group showed the lowest NfL levels, while treatment groups exhibited increments. Conclusion This study highlights the neuroprotective potential of bexarotene and icariin in a diabetic rat model, evidenced by significant changes in GFAP levels. The lack of significant changes in BDNF and NfL suggests that longer study durations may be necessary to observe these effects. Future research should include extended study periods, larger sample sizes, varied dosages, and comprehensive behavioral assessments to better understand the therapeutic potential of these agents.