Amelioration of D-galactose-induced hyposalivation in aging rats by the GLP-1 receptor agonist Exendin-4

Xerostomia is commonly associated with aging, diabetes, and other systemic conditions. It disrupts oral homeostasis and consequently elevates the likelihood of dental caries, periodontal disorders, and oral infections. Accordingly, mitigating xerostomia is expected to help prevent these oral pathologies and improve patients' quality of life. Because rodents cannot report subjective sensations of oral dryness, experimentally induced hyposalivation is used as an appropriate surrogate to study underlying mechanisms and potential interventions. Exendin-4 is a GLP-1 receptor agonist initially discovered in the saliva of Heloderma suspectum. It was developed as an antidiabetic medication. Using a D-galactose-based aging model in rats, this study explored the capacity of Exendin-4 to restore salivary secretion. An experimental model of hyposalivation resembling aging was created by giving rats D-galactose (300 mg/kg, intraperitoneally) each day for 7 weeks. Thereafter, Exendin-4 was provided for 2 weeks at two dosage levels (0.5 and 1 μg/head). We evaluated improvements by measuring salivary flow rates and conducting various histological and biochemical analyses. Exendin-4 treatment significantly reversed the age-related decline in salivary secretion and preserved the typical morphological characteristics of acinar cells. Histochemical staining indicated that both acidic and neutral mucin accumulation were reduced, and TUNEL analysis revealed a decrease in apoptotic cells in the salivary gland. In summary, Exendin-4 exhibits beneficial effects on D-galactose-induced hyposalivation by improving salivary secretion, preserving glandular structure, and decreasing apoptotic cell death. Thus, Exendin-4 may improve salivary secretion in animal models of aging-related hyposalivation.