Abstract
<jats:p>Repetitive mild traumatic brain injury (TBI) under chronic alcohol intoxication (CAI) represents a prevalent comorbid condition associated with neuroinflammation, metabolic disturbances, and an increased risk of chronic traumatic encephalopathy. The search for pharmacological agents capable of simultaneously mitigating neural tissue damage and correcting systemic metabolic dysregulation is of considerable scientific and clinical relevance. This study investigated the effects of quercetin on biomarkers of neural tissue injury, systemic inflammatory response parameters, and carbohydrate and lipid metabolism in rats subjected to repetitive mild TBI under CAI. The experiment was performed on Wistar rats divided into three groups: Group 1 (Control I) – intact animals; Group 2 – rats exposed to TBI combined with CAI (Control II); Group 3 – rats receiving an intraperitoneal water-soluble form of quercetin (Corvitin) at 100 mg/kg for 14 days following TBI with CAI. TBI was induced using a free-weight drop method (five sessions at 48-hour intervals), while CAI was modeled by administering 40% ethanol at 12 ml/kg for 14 days. Serum concentrations of neuron-specific enolase (NSE), calcium-binding protein S100B, tumor necrosis factor-alpha (TNF-α), interleukins (IL)-6 and IL-10, glucose, insulin, and lipid profile parameters were measured, and the HOMA-IR index was calculated. TBI combined with CAI resulted in marked neuroinflammation and systemic inflammatory response, as evidenced by significant elevations in neural tissue injury markers, increased serum levels of pro-inflammatory cytokines TNF-α and IL-6, and the development of insulin resistance and dyslipidemia. Administering quercetin led to significant reductions in serum NSE (61.9%), S100B (56.3%), TNF-α (40.8%), and IL-6 (42.0%), as well as a 187.5% increase in IL-10. Furthermore, compared with Group 2 values, the bioflavonoid reduced glucose by 30.5%, insulin by 68.7%, very low-density lipoproteins (VLDL) by 42.3%, triglycerides by 41.9%, and HOMA-IR by 78.4%. These findings indicate that quercetin exerts pronounced neuroprotective and anti-inflammatory effects under conditions of TBI combined with CAI, effectively lowering serum biomarkers of neural tissue injury and pro-inflammatory cytokines, while enhancing the anti-inflammatory cytokine IL-10. Moreover, quercetin efficiently restores metabolic homeostasis by normalising glycemia, improving insulin sensitivity, and reducing dyslipidemia.</jats:p>