Therapeutic Potential of Quercetin on A Rat Model of Radiation-Induced Brain Neurotoxicities: Insights from Behavioural and Biochemical Analyses
نویسندگان
1 Department of Radiation Oncology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
2 Mobility Impairment Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
3 Department of Pharmacology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
4 Mobility Impairment Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
5 Student Research Committee, Babol University of Medical Sciences, Babol, Iran
6 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
7 Department of Pathology, Babol Branch, Islamic Azad University, Babol, Iran
8 Student Research Committee, Babol University of Medical Sciences, Babol, Iran
doi
10.22074/cellj.2025.2046460.1730چکیده
Objective: Radiation therapy (RT), while effective for cancer, can cause significant neurotoxicity. This study evaluatedthe neuroprotective potential of quercetin against radiation-induced brain injury (RIBI) in an adult male Wistar rat model.Materials and Methods: In this experimental study, 42 adult male rats were randomised into control, RT, RT+vehicle (Tween),and RT+quercetin (2.5, 5, or 10 mg/kg) groups. The RT-treated animals received eight fractions of 40 Gy cranial radiation.Quercetin was administered daily for four weeks in the appropriate groups. Spatial memory was assessed via the Morris watermaze (MWM) test. Serum biomarkers of tumour necrosis factor-α (TNF-α), IL-2, ferric reducing antioxidant power (FRAP),malondialdehyde (MDA), and hippocampal histopathology [cornu ammonis (CA1), dentate gyrus (DG)] were analysed.Results: RT significantly impaired spatial learning. This deficit was significantly ameliorated by all tested quercetindoses during the training trials. RT induced a marked increase in serum TNF-α levels, from a baseline of 113.8 ± 19.4ng/L in the control group to 257.8 ± 28.8 ng/L (P=0.005). Quercetin treatment effectively reversed this proinflammatoryresponse by significantly reducing TNF-α concentrations at all administered doses. The 2.5 mg/kg dose reduced levelsto 121.7 ± 19.5 ng/L (P=0.008). A key finding was the potent effect of the 5 mg/kg dose on oxidative damage, asit produced the most significant reduction in MDA levels compared to the RT group. Histological analysis showedthat quercetin enhanced neuronal survival; the 2.5 and 5 mg/kg doses significantly increased neuronal counts in thehippocampal CA1 and DG regions.Conclusion: The Quercetin exhibited a protective effect against radiation-induced neurotoxicity in the adult male Wistarrats by improving behavioural, biochemical, and histological outcomes. The 5 mg/kg dose provided the most consistentbenefit. These findings suggest that quercetin, particularly at 5 mg/kg, could serve as a potential adjunctive therapy tomitigate neurotoxic side effects associated with RT.
