Effects of High-Dextrose Intake on the Structural and Functional Properties of the Small Intestine in Young-Maturing and Middle-Aged Rats

Excessive dietary dextrose intake and its misuse in sports raise significant concerns about health outcomes across life stages. To investigate how biological maturity influences small intestinal responsiveness to dextrose overexposure, we subjected 1-month-old (young maturing) and 14-month-old (middle-aged) male Wistar rats to a 20% or 60% dextrose drinking regimen for 8 weeks. The middle-aged rats receiving the 60% dextrose solution exhibited the most pronounced alterations, including compromised barrier integrity, reduced crypt proliferation, and accelerated enterocyte apoptosis and necrosis. These structural changes coincided with weakened antioxidant defences, tissue iron accumulation, and elevated lipid peroxidation. Altered neuroendocrine and purinergic pathways, marked by increased serotonin, neuron-specific enolase (NSE), cytosolic high mobility group box 1 (HMGB1), and ATP synthase, alongside downregulated P2X7 receptor expression and a reduced nuclear factor kappa B p65/nuclear factor erythroid 2-related factor 2 (NF-κB p65/Nrf2) ratio, indicate potential observational associations with metabolic exhaustion and impaired inflammatory responsiveness under a chronic high-dextrose regimen. In conclusion, while fasting homeostatic model assessment of insulin resistance (HOMA-IR) values remained stable, a high-dextrose drinking regimen promotes maturity-dependent small intestinal changes and molecular signalling weakness, providing a preliminary pathophysiological framework for understanding potential health outcomes of dextrose overexposure across different life stages.