Vildagliptin-Omega-3 combination therapy mitigates the diabetic effects on rats sublingual salivary glands via anti-oxidative and anti-apoptotic mechanisms

Authors

  • Ahmed O. Galal
  • Lashin S. Ali
  • Osama I. Ramadan
  • Reda S. Taha
  • Moaaz M. Awad
  • Osama M. Abdelhay
  • Ala’a Alasmar
  • Anas A. Darwish
  • Afnan I. Elgndy
  • Asmaa M. Meghawry
  • Mahmoud Diab
  • Nourelhuda A. Mohammed
  • Fatma M. Abd-Allah
  • Ibrahim M. Amr
  • Mohammed E. Elmitwalli
  • Nassar A. A. Omar
  • Ahmed E. Amer
  • Alsayed A. Abdel-Hady

DOI:

https://doi.org/10.31989/ffhd.v16i4.1937

Abstract

Background: Patients with diabetes mellitus (DM) frequently have xerostomia (dry mouth) and hyposalivation. Whether xerostomia and hyposalivation are more common in DM patients than non-DM individuals is unclear.

Aim of the study: We aimed to detect the diabetic effects on the sublingual salivary gland and investigate the therapeutic potential of Vildagliptin (a dipeptidyl peptidase-4 (DPP-4) inhibitor) and omega-3 polyunsaturated fatty acids (PUFAs), alone and in combination, in protecting sublingual salivary glands in streptozotocin (STZ)-induced diabetic rats.

Methods: Forty male albino rats were randomly allocated into control, diabetic untreated, diabetic + Vildagliptin, diabetic + omega-3, and diabetic + combination groups. After 8 weeks, biochemical markers of oxidative stress including: Glutathione (GSH); Malondialdehyde (MDA); Nitric Oxide (NO); Superoxide Dismutase (SOD); Total Antioxidant Capacity (TAC), and inflammation markers as Interleukins ((IL-1β, IL-6) and Tumor Necrosis Factor (TNF) and histological outcomes (acinar integrity, mucin content, apoptosis) were analyzed.

Results: Induction of diabetes in rats caused structural changes in the sublingual gland associated with fibrotic, apoptotic and inflammatory changes, treatment of diabetes with vildagliptin enhanced the previous changes, butthe combination therapy (vildagliptin plus omega 3) significantly reduced oxidative stress, suppressed inflammation, and preserved gland structure compared to monotherapies.

Conclusion: The synergistic efficacy of Vildagliptin-omega-3 in mitigating diabetic salivary gland damage, proposing a novel therapeutic strategy.

Novelty of the Study: Although Omega-3 and vildagliptin, a DPP-4 inhibitor, are both well-known for their metabolic and antioxidant advantages, this study is the first to show how they integrate to protect salivary gland architecture from diabetes-related damage via dual mechanisms (antioxidative and antiapoptotic). This provides a novel therapeutic approach for treating diabetic xerostomia (dry mouth) with glycemic control.

Keywords: Diabetes mellitus; salivary glands; Vildagliptin; Omega-3; xerostomia

Published

2026-04-23

Issue

Section

Research Articles